Search

This study used a typical four-item search display to investigate top-down control over attentional capture in an additional singleton paradigm. By manipulating target and distractor color and shape, stimulus saliency relative to the remaining items was systematically varied. One group of participants discriminated the side of a dot within a salient orange target (ST group) presented with green circles (fillers) and a green diamond distractor. A second group discriminated the side of the dot within a green diamond target presented with green circle fillers and a salient orange square distractor (SD group). Results showed faster reaction times and a shorter latency of the N2pc component in the event-related potential (ERP) to the more salient targets in the ST group. Both salient and less salient distractors elicited Pd components of equal amplitude. Behaviorally, no task interference was observed with the less salient distractor, indicating the prevention of attentional capture. However, reaction times were slower in the presence of the salient distractor, which conflicts with the hypothesis that the Pd reflects proactive distractor suppression. Contrary to recent proposals that elicitation of the Pd requires competitive interactions with a target, we found a greater Pd amplitude when the distractor was presented alone. Alpha-band amplitudes decreased during target processing (event-related desynchronization), but no significant amplitude enhancement was observed at electrodes contralateral to distractors regardless of their saliency. The results demonstrate independent neural mechanisms for target and distractor processing and support the view that top-down guidance of attention can be offset (counteracted) by relative stimulus saliency., (© 2022. The Author(s).)

Objective: Choroid plexus carcinoma (CPC) is a rare, primarily intraventricular neoplasm. Extent of resection correlates with improved outcomes but is limited due to tumor vascularity and size. Evidence on optimal surgical management and molecular drivers of recurrence remains limited. Here the authors characterize a case of multiply recurrent CPC treated with sequential endoscopic removals over 10 years and highlight its genomic properties., Observations: Five years after standard treatment, a 16-year-old female presented with a distant intraventricular recurrence of CPC. Whole exome sequencing revealed NF1, PER1, and SLC12A2 mutations, FGFR3 gain, and no TP53 alterations. Repeat sequencing on recurrences 4 and 5 years later showed persistent NF1 and FGFR3 alterations. Methylation profiling was consistent with plexus tumor, subclass pediatric B. Short-term magnetic resonance imaging detected four total isolated recurrences, all treated with complete endoscopic resections at 5, 6.5, 9, and 10 years after initial diagnosis. Mean hospital stay for all recurrences was 1 day with no complications., Lessons: The authors describe a patient with four isolated recurrences of CPC over a decade, each treated with complete endoscopic removal, and identify unique molecular alterations that persisted without TP53 alterations. These outcomes support frequent neuroimaging to facilitate endoscopic surgical removal following early detection of CPC recurrence.

The pathophysiological progress of Parkinson's disease leads through degeneration of dopaminergic neurons in the substantia nigra to complete cell death and lack of dopamine in the striatum where it modulates motor functions. Transplantation of dopaminergic stem cell-derived neurons is a possible therapy to restore dopamine levels. We have previously presented multifunctional pyrolytic carbon coated leaky optoelectrical fibers (LOEFs) with laser ablated micro-optical windows (µOWs) as carriers for channelrhodopsin-2 modified optogenetically active neurons for light-induced on-demand dopamine release and amperometric real-time detection. To increase the dopamine release by stimulating a larger neuronal population with light, we present here a novel approach to generate µOWs through laser ablation around the entire circumference of optical fibers to obtain Omni-LOEFs. Cyclic voltammetric characterization of the pyrolytic carbon showed that despite the increased number of µOWs, the electrochemical properties were not deteriorated. Finally, we demonstrate that the current recorded during real-time detection of dopamine upon light-induced stimulation of neurons differentiated on Omni-LOEFs is significantly higher compared to recordings from the same number of cells seeded on LOEFs with µOWs only on one side. Moreover, by varying the cell seeding density, we show that the recorded current is proportional to the dimension of the cell population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

There is much debate about the neural mechanisms that achieve suppression of salient distracting stimuli during visual search. The proactive suppression hypothesis asserts that if exposed to the same distractors repeatedly, these stimuli are actively inhibited before attention can be shifted to them. A contrasting proposal holds that attention is initially captured by salient distractors but is subsequently withdrawn. By concurrently measuring stimulus-driven and intrinsic brain potentials in 36 healthy human participants, we obtained converging evidence against early proactive suppression of distracting input. Salient distractors triggered negative event-related potentials (N1pc/N2pc), enhanced the steady-state visual evoked potential (SSVEP) relative to non-salient (filler) stimuli, and suppressed contralateral relative to ipsilateral alpha-band amplitudes-three electrophysiological measure associated with the allocation of attention-even though these distractors did not interfere with behavioral responses to the search targets. Furthermore, these measures indicated that both stimulus-driven and goal-driven allocations of attention occurred in conjunction with one another, with the goal-driven effect enhancing and prolonging the stimulus-driven effect. These results provide a new perspective on the traditional dichotomy between bottom-up and top-down attentional allocation. Control experiments revealed that continuous marking of the locations at which the search display items were presented resulted in a dramatic and unexpected conversion of the target-elicited N2pc into a shorter-latency N1pc in association with faster reaction times to the targets., Competing Interests: Declaration of Competing Interests The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

This study used electrophysiological measures to investigate how attention is deployed to target and distractor stimuli during visual search using search displays with a small set-size. Participants viewed randomized sequences of two-item displays that consisted of either a target and a distractor (differing in color) or a pair of task-irrelevant filler stimuli having a third color, all presented in an ongoing stream of flickering gray circles. The allocation of attention was assessed by concurrent recordings of steady-state visual evoked potentials (SSVEPs) elicited by the flickering displays and perturbations of the endogenous alpha rhythm following each type of display. The aim was to test a central prediction of the signal suppression hypothesis, namely that the processing of distractors will be proactively suppressed below the level of filler stimuli. Amplitude modulations of both the SSVEP and the lateralized alpha rhythm provided converging evidence against early proactive suppression of highly salient distractors. Instead, these electrophysiological measures were consistent with the view that in this type of two-stimulus search task there is an initial capture of attention by all color-change stimuli (targets, distractors, and fillers) followed by a further focusing of attention upon the target, with no evidence for suppression of the distractor., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Feature-based attention serves the separation of relevant from irrelevant features. While global amplification of attended features is coherently described as a key mechanism for feature-based attention, nature and constituting factors of neural suppressive interactions are far less clear. One aspect of global amplification is its flexible modulation by the task relevance of the to-be-attended stimulus. We examined whether suppression is similarly modulated by their respective task relevance or is mandatory for all unattended features. For this purpose, participants saw a display of randomly moving dots with 3 distinct colors and were asked to report brief events of coherent motion for a cued color. Of the 2 unattended colored clouds, one contained distracting motion events while the other was irrelevant and without such motion events throughout the experiment. We used electroencephalography-derived steady-state visual-evoked potentials to investigate early visual processing of the attended, unattended, and irrelevant color under sustained feature-based attention. The analysis revealed a biphasic process with an early amplification of the to-be-attended color followed by suppression of the to-be-ignored color relative to a pre-cue baseline. Importantly, the neural dynamics for the unattended and always irrelevant color were comparable. Suppression is thus a mandatory mechanism affecting all unattended stimuli irrespective of their task relevance., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Super-resolution ultrasound imaging (SRUS) enables in vivo microvascular imaging of deeper-lying tissues and organs, such as the kidneys or liver. The technique allows new insights into microvascular anatomy and physiology and the development of disease-related microvascular abnormalities. However, the microvascular anatomy is intricate and challenging to depict with the currently available imaging techniques, and validation of the microvascular structures of deeper-lying organs obtained with SRUS remains difficult. Our study aimed to directly compare the vascular anatomy in two in vivo 2D SRUS images of a Sprague-Dawley rat kidney with ex vivo μCT of the same kidney. Co-registering the SRUS images to the μCT volume revealed visually very similar vascular features of vessels ranging from ~ 100 to 1300 μm in diameter and illustrated a high level of vessel branching complexity captured in the 2D SRUS images. Additionally, it was shown that it is difficult to use μCT data of a whole rat kidney specimen to validate the super-resolution capability of our ultrasound scans, i.e., validating the actual microvasculature of the rat kidney. Lastly, by comparing the two imaging modalities, fundamental challenges for 2D SRUS were demonstrated, including the complexity of projecting a 3D vessel network into 2D. These challenges should be considered when interpreting clinical or preclinical SRUS data in future studies., (© 2021. The Author(s).)

Background and purpose - We noted several adverse events in patients in whom the first version of the STRYDE limb-lengthening nail (NuVasive Specialized Orthopaedics, San Diego, CA) had been implanted. Pain, osteolysis, periosteal reactions, and cortical hypertrophy at the nail junction were noted. Here, we present the analysis of 23 retrieved STRYDE implants.Materials and methods - We undertook visual inspection of the retrieved nails and screws, mechanical evaluation of the junction, micro-CT analyses, microscopic inspection of the bushing, screws, screw holes, and separated parts of the implants. Positive material identification (PMI) and energy-dispersive X-ray spectroscopy (EDS) were used to analyze the chemical composition. The hardness of the material was also investigated.Results - 20/23 retrieved nails had visible signs of corrosion, i.e., discoloration at the telescopic junction. Micro-CT verified corrosion attacks in 12/12 scanned bushings. Corrosion, predominantly mechanically assisted crevice corrosion, was observed at the locking screws and screw holes in 20/23 nails. Biological material inside the nail was observed in addition to oozing from the junction of 2 nails during hardware removal, which was experimentally reproducible. Notably, the mechanical construction of the bushing changed from PRECICE P2 to STRYDE nails.Interpretation - STRYDE nails are not hermetically sealed, and liquid can pass the bushing. Biodur 108 itself is corrosion resistant; however, mechanically assisted crevice corrosion of the bushing, locking screws, and screw holes may be aggravated due to manufacturing aiming for increased strength and hardness of the alloy.Observing several adverse events, we recently published a nationwide cross-sectional analysis of all 30 STRYDE limb- lengthening nails (NuVasive, Specialized Orthopedics, San Diego, CA) that were implanted in Denmark (Rölfing et al. 2021a). 27/30 STRYDE nails have now been removed and we present data from metallurgical analysis of 23 of the retrieved implants.

Bilateral in-phase (IP) and anti-phase (AP) movements represent two fundamental modes of bilateral coordination that are essential for daily living. Although previous studies have shown that aging is behaviorally associated with decline in bilateral coordination, especially in AP movements, the underlying neural mechanisms remain unclear. Here, we use kinematic measurements and electroencephalography to compare motor performance of young and older adults executing bilateral IP and AP hand movements. On the behavioral level, inter-limb synchronization was reduced during AP movements compared to IP and this reduction was stronger in the older adults. On the neural level, we found interactions between group and condition for task-related power change in different frequency bands. The interaction was driven by smaller alpha power decreases over the non-dominant cortical motor area in young adults during IP movements and larger beta power decreases over the midline region in older adults during AP movements. In addition, the decrease in inter-limb synchronization during AP movements was predicted by stronger directional connectivity in the beta-band: an effect more pronounced in older adults. Our results therefore show that age-related differences in the two bilateral coordination modes are reflected on the neural level by differences in alpha and beta oscillatory power as well as interhemispheric directional connectivity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Microscale devices are promising tools to overcome specific challenges within oral drug delivery. Despite the availability of advanced high-quality imaging techniques, visualization and tracking of microscale devices in the gastrointestinal (GI) tract is still a challenge. This work explores the possibilities of applying planar X-ray imaging and computed tomography (CT) scanning for visualization and tracking of microscale devices in the GI tract of rats. Microcontainers (MCs) are an example of microscale devices that have shown great potential as an oral drug delivery system. Barium sulfate (BaSO 4 ) loaded into the cavity of the MCs increases their overall X-ray contrast, which allows them to be easily tracked. The BaSO 4 -loaded MCs are quantitatively tracked throughout the entire GI tract of rats by planar X-ray imaging and visualized in 3D by CT scanning. The majority of the BaSO 4 -loaded MCs are observed to retain in the stomach for 0.5-2 h, enter the cecum after 3-4 h, and leave the cecum and colon 8-10 h post-administration. The imaging approaches can be adopted and used with other types of microscale devices when investigating GI behavior in, for example, preclinical trials and potential clinical studies.

Alpha, the most prominent human brain rhythm, might reflect a mechanism of functional inhibition for gating neural processing. This concept has been derived predominantly from local measures of inhibition, while large-scale network mechanisms to guide information flow are largely unknown. Here, we investigated functional connectivity changes on a whole-brain level by concurrent transcranial alternating current stimulation (tACS) and resting-state functional MRI in humans. We specifically focused on somatosensory alpha-band oscillations by adjusting the tACS frequency to each individual´s somatosensory (mu-) alpha peak frequency (mu-tACS). Potential differences of Eigenvector Centrality of primary somatosensory cortex (S1) as well as on a whole brain level between mu-tACS and sham were analyzed. Our results demonstrate that mu-tACS induces a locally-specific decrease in whole-brain functional connectivity of left S1. An additional exploratory analysis revealed that this effect primarily depends on a decrease in functional connectivity between S1 and a network of regions that are crucially involved in somatosensory processing. Furthermore, the decrease in functional centrality was specific to mu-tACS and was not observed when tACS was applied in the gamma-range in an independent study. Our findings provide evidence that modulated somatosensory (mu-) alpha-activity may affect whole-brain network level activity by decoupling primary sensory areas from other hubs involved in sensory processing., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Today's consumer electronics are made from nonrenewable and toxic components. They are also rigid, bulky, and manufactured in an energy-inefficient manner via CO 2 -generating routes. Though petroleum-based polymers such as polyethylene terephthalate and polyethylene naphthalate can address the rigidity issue, they have a large carbon footprint and generate harmful waste. Scalable routes for manufacturing electronics that are both flexible and ecofriendly (Fleco) could address the challenges in the field. Ideally, such substrates must incorporate into electronics without compromising device performance. In this work, we demonstrate that a new type of wood-based [nanocellulose (NC)] material made via nanosilicate (NS) reinforcement can yield flexible electronics that can bend and roll without loss of electrical function. Specifically, the NSs interact electrostatically with NC to reinforce thermal and mechanical properties. For instance, films containing 34 wt % of NS displayed an increased young's modulus (1.5 times), thermal stability (290 → 310 °C), and a low coefficient of thermal expansion (40 ppm/K). These films can also easily be separated and renewed into new devices through simple and low-energy processes. Moreover, we used very cheap and environmentally friendly NC from American Value Added Pulping (AVAP) technology, American Process, and therefore, the manufacturing cost of our NS-reinforced NC paper is much cheaper ($0.016 per dm -2 ) than that of conventional NC-based substrates. Looking forward, the methodology highlighted herein is highly attractive as it can unlock the secrets of Fleco electronics and transform otherwise bulky, rigid, and "difficult-to-process" rigid circuits into more aesthetic and flexible ones while simultaneously bringing relief to an already-overburdened ecosystem.

Non-invasive brain stimulation (NIBS) techniques such as transcranial alternating current stimulation (tACS) have recently become extensively utilized due to their potential to modulate ongoing neuronal oscillatory activity and consequently to induce cortical plasticity relevant for various cognitive functions. However, the neurophysiological basis for stimulation effects as well as their inter-individual differences is not yet understood. In the present study, we used a closed-loop electroencephalography-tACS(EEG-tACS) protocol to examine the modulation of alpha oscillations generated in occipito-parietal areas. In particular, we investigated the effects of a repeated short-time intermittent stimulation protocol (1 s in every trial) applied over the visual cortex (Cz and Oz) and adjusted according to the phase and frequency of visual alpha oscillations on the amplitude of these oscillations. Based on previous findings, we expected higher increases in alpha amplitudes for tACS applied in-phase with ongoing oscillations as compared to an application in anti-phase and this modulation to be present in low-alpha amplitude states of the visual system (eyes opened, EO) but not high (eyes closed, EC). Contrary to our expectations, we found a transient suppression of alpha power in inter-individually derived spatially specific parieto-occipital components obtained via the estimation of spatial filters by using the common spatial patterns approach. The amplitude modulation was independent of the phase relationship between the tACS signal and alpha oscillations, and the state of the visual system manipulated via closed- and open-eye conditions. It was also absent in conventionally analyzed single-channel and multi-channel data from an average parieto-occipital region. The fact that the tACS modulation of oscillations was phase-independent suggests that mechanisms driving the effects of tACS may not be explained by entrainment alone, but rather require neuroplastic changes or transient disruption of neural oscillations. Our study also supports the notion that the response to tACS is subject-specific, where the modulatory effects are shaped by the interplay between the stimulation and different alpha generators. This favors stimulation protocols as well as analysis regimes exploiting inter-individual differences, such as spatial filters to reveal otherwise hidden stimulation effects and, thereby, comprehensively induce and study the effects and underlying mechanisms of tACS., (Copyright © 2020 Zarubin, Gundlach, Nikulin, Villringer and Bogdan.)

Objective: To characterize the presence and nature of discrete behavioral phenotypes and their correlates in a cohort of youth with new and recent onset focal and generalized epilepsies., Methods: The parents of 290 youth (age = 8-18 years) with epilepsy (n = 183) and typically developing participants (n = 107) completed the Child Behavior Checklist for children aged 6-18 from the Achenbach System of Empirically Based Assessment. The eight behavior problem scales were subjected to hierarchical clustering analytics to identify behavioral subgroups. To characterize the external validity and co-occurring comorbidities of the identified subgroups, we examined demographic features (age, gender, handedness), cognition (language, perception, attention, executive function, speed), academic problems (present/absent), clinical epilepsy characteristics (epilepsy syndrome, medications), familial factors (parental intelligence quotient, education, employment), neuroimaging features (cortical thickness), parent-observed day-to-day executive function, and number of lifetime-to-date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses., Results: Hierarchical clustering identified three behavioral phenotypes, which included no behavioral complications (Cluster 1, 67% of epilepsy cohort [n = 122]), nonexternalizing problems (Cluster 2, 11% of cohort [n = 21]), and combined internalizing and externalizing problems (Cluster 3, 22% of cohort [n = 40]). These behavioral phenotypes were characterized by orderly differences in personal characteristics, neuropsychological status, history of academic problems, parental status, cortical thickness, daily executive function, and number of lifetime-to-date DSM-IV diagnoses. Cluster 1 was most similar to controls across most metrics, whereas Cluster 3 was the most abnormal compared to controls. Epilepsy syndrome was not a predictor of cluster membership., Significance: Youth with new and recent onset epilepsy fall into three distinct behavioral phenotypes associated with a variety of co-occurring features and comorbidities. This approach identifies important phenotypes of behavior problem presentations and their accompanying factors that serve to advance clinical and theoretical understanding of the behavioral complications of children with epilepsy and the complex conditions with which they co-occur., (© 2020 International League Against Epilepsy.)

Monolithic silicon carbide supported ionic liquid-phase (SILP) Rh-catalysts have very recently been introduced for gas-phase hydroformylation as an important step toward industrial upscaling. This study investigates the monolithic catalyst system in combination with different impregnation procedures with non-invasive magnetic resonance imaging (MRI). The findings were supported by X-ray microtomography (micro-CT) data of the monolithic pore structure and a catalytic performance test of the catalyst system for 1-butene gas-phase hydroformylation. MRI confirmed a homogeneous impregnation of the liquid phase throughout the full cross-section of the cylindrical monoliths. Consistent impregnations from one side to the other of the monoliths were achieved with a stabilizer in the system that helped preventing inhomogeneous rim formation. External influences relevant for industrial application, such as long-term storage and temperature exposure, did not affect the homogeneous liquid-phase distribution of the catalyst. The work elucidates important parameters to improve liquid-phase catalyst impregnation to obtain efficient monolithic catalysts for industrial exploitation in gas-phase hydroformylation as well as other important industrial processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Our visual system extracts the emotional meaning of human facial expressions rapidly and automatically. Novel paradigms using fast periodic stimulations have provided insights into the electrophysiological processes underlying emotional content extraction: the regular occurrence of specific identities and/or emotional expressions alone can drive diagnostic brain responses. Consistent with a processing advantage for social cues of threat, we expected angry facial expressions to drive larger responses than neutral expressions. In a series of four EEG experiments, we studied the potential boundary conditions of such an effect: (i) we piloted emotional cue extraction using 9 facial identities and a fast presentation rate of 15 Hz (N = 16); (ii) we reduced the facial identities from 9 to 2, to assess whether (low or high) variability across emotional expressions would modulate brain responses (N = 16); (iii) we slowed the presentation rate from 15 Hz to 6 Hz (N = 31), the optimal presentation rate for facial feature extraction; (iv) we tested whether passive viewing instead of a concurrent task at fixation would play a role (N = 30). We consistently observed neural responses reflecting the rate of regularly presented emotional expressions (5 Hz and 2 Hz at presentation rates of 15 Hz and 6 Hz, respectively). Intriguingly, neutral expressions consistently produced stronger responses than angry expressions, contrary to the predicted processing advantage for threat-related stimuli. Our findings highlight the influence of physical differences across facial identities and emotional expressions., Competing Interests: The authors have declared that no competing interests exist.

Climate change and invasive species threaten biodiversity, yet rigorous monitoring of their impact can be costly. Citizen science is increasingly used as a tool for monitoring exotic species, because citizens are geographically and temporally dispersed, whereas scientists tend to cluster in museums and at universities. Here we report on the establishment of the first exotic ant taxon ( Tetramorium immigrans ) in Denmark, which was discovered by children participating in The Ant Hunt. The Ant Hunt is a citizen science project for children that we ran in 2017 and 2018, with a pilot study in 2015. T. immigrans was discovered in the Botanical Garden of the Natural History Museum of Denmark in 2015 and confirmed as established in 2018. This finding extends the northern range boundary of T. immigrans by almost 460 km. Using climatic niche modelling, we compared the climatic niche of T. immigrans in Europe with that of T. caespitum based on confirmed observations from 2006 to 2019. T. immigrans and T. caespitum had a 13% niche overlap, with T. immigrans showing stronger occurrence in warmer and drier areas compared to T. caespitum . Mapping the environmental niches onto geographic space identified several, currently uninhabited, areas as climatically suitable for the establishment of T. immigrans . Tetramorium immigrans was sampled almost three times as often in areas with artificial surfaces compared to T. caespitum , suggesting that T. immigrans may not be native to all of Europe and is being accidentally introduced by humans. Overall, citizen scientists collected data on ants closer to cities and harbours than scientists did and had a stronger bias towards areas of human disturbance. This increased sampling effort in areas of likely introduction of exotic species naturally increases the likelihood of discovering species sooner, making citizen science an excellent tool for exotic species monitoring, as long as trained scientists are involved in the identification process., Competing Interests: The authors declare that they have no competing interests., (© 2020 Sheard et al.)

The steady-state visual evoked potential (SSVEP), an electrophysiological marker of attentional resource allocation, has recently been demonstrated to serve as a neural signature of emotional content extraction from a rapid serial visual presentation (RSVP). SSVEP amplitude was reduced for streams of emotional relative to neutral scenes passively viewed at 6 Hz (~167 ms per image), but it was enhanced for emotional relative to neutral scenes when viewed as 4 Hz RSVP (250 ms per image). Here, we investigated whether these seemingly contradictory observations may be related to different dynamics in the allocation of attentional resources as a consequence of stimulation frequency. To this end, we advanced our distraction paradigm by presenting a visual foreground task consisting of randomly moving squares flickering at 15 Hz superimposed on task-irrelevant RSVP streams shown at 6 or 4 Hz, which could unpredictably switch from neutral to unpleasant content during the trial or remained neutral. Critically, our findings demonstrate that affective distractors captured attentional resources more strongly than their neutral counterparts, irrespective of whether they were presented at 6 or 4 Hz rate. Moreover, the emotion-dependent attentional deployment from the foreground task was temporally preceded by sustained sensory facilitation in response to emotional background images. Together, present findings provide evidence for rapid sustained visual facilitation but a rather slow attentional bias in favor of emotional distractors in early visual areas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We numerically investigate the threshold of black-hole formation in the gravitational collapse of electromagnetic waves in axisymmetry. We find approximate power-law scaling ρ_{max}∼(η_{*}-η)^{-2γ} of the maximum density in the time evolution of near-subcritical data with γ≃0.145, where η is the amplitude of the initial data. We directly observe approximate discrete self-similarity in near-critical time evolutions with a log-scale echoing period of Δ≃0.55. The critical solution is approximately the same for two families of initial data, providing some evidence of universality. Neither the discrete self-similarity nor the universality, however, are exact. We speculate that the absence of an exactly discrete self-similarity might be caused by the interplay of electromagnetic and gravitational wave degrees of freedom, or by the presence of higher-order angular multipoles, or both, and discuss implications of our findings for the critical collapse of vacuum gravitational waves.

Microfabrication techniques have been applied to develop micron-scale devices for oral drug delivery with a high degree of control over size, shape and material composition. Recently, microcontainers have been introduced as a novel approach to obtain unidirectional release to avoid luminal drug loss, enhance drug permeation, protect drug payload from the harsh environment of the stomach, and explore the ability for targeted drug delivery. However, in order to eventually pave the way for real life applications of these microfabricated drug delivery systems, it is necessary to fabricate them in biodegradable materials approved for similar applications and with strategies that potentially allow for large scale production. In this study, we for the first time evaluate biodegradable microcontainers for oral drug delivery. Asymmetric poly-ε-caprolactone (PCL) microcontainers with a diameter of 300 μm and a volume of 2.7 nL are fabricated with a novel single-step fabrication process. The microcontainers are loaded with the model drug paracetamol and coated with an enteric pH-sensitive Eudragit® S100 coating to protect the drug until it reaches the desired location in the small intestine. In vitro dissolution studies are performed to assess the drug load and release profile of the PCL microcontainers. Finally, in vivo studies in rats showed a higher bioavailability compared to conventional dosage forms and confirm the potential of biodegradable microcontainers for oral drug delivery.

Oral delivery of proteins and peptides is one of the main challenges in pharmaceutical drug development. Microdevices have the possibility to protect the therapeutics until release is desired, avoiding losses by degradation. One type of microdevice is polymeric microcontainers. In this study, lysozyme is chosen as model protein and loaded into microcontainers with the permeation enhancer sodium decanoate (C10). The loaded microcontainers are sealed and functionalized by applying polymeric lids onto the cavity of the devices. The first lid is poly(lactic-co-glycolic) acid (PLGA) and on top of this either polyethylene glycol (PEG) or chitosan is applied (PLGA+PEG or PLGA+chitosan, respectively). The functionalization is evaluated in vitro for morphology, drug release, and mucoadhesive properties. These are coupled with in vitro and ex vivo studies using Caco-2 cells, Caco-2/HT29-MTX-E12 co-cultures, and porcine intestinal tissue. PLGA+chitosan shows slower release compared to PLGA+PEG or only PLGA in buffer and the transport of lysozyme across cell cultures is not enhanced compared to the bulk powder. Microcontainers coated with chitosan or PEG demonstrate a three times stronger adhesion during ex vivo mucoadhesion studies compared to samples without coatings. Altogether, functionalized microcontainers with mucoadhesive properties and tunable release for oral protein delivery are developed and characterized., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The integrated object account predicts that attention is spread across all features that constitute one object, regardless of their task relevance. We challenge that prediction with a novel stimulation technique that allows for simultaneous electrophysiological measurements of the allocation of attention to two distinct features within one object. A rotating square that flickers in different colors evoked two distinct steady-state visual evoked potentials (SSVEPs) for rotation and color, respectively. If the integrated object account were true, we would expect identical SSVEP amplitudes regardless of what feature participants attended. We found greater SSVEP amplitudes for the to-be-attended feature compared with the to-be-ignored feature. SSVEP amplitudes averaged across both features were significantly reduced when participants attended to both features, which was mirrored in behavioral costs, implying competitive interactions or a division of attentional resources. Surprisingly, this reduction in amplitude was mainly driven by the SSVEP amplitude elicited by color changes. In conclusion, our results challenge the integrated object account and highlight the extent to which color is "special" within feature space.

In a recent electrophysiological study, we reported on global facilitation but local suppression of color stimuli in feature-based attention in human early visual cortex. Subjects attended to one of two centrally located superimposed red/blue random dot kinematograms (RDKs). Task-irrelevant single RDKs in the same colors were presented in the left and right periphery, respectively. Suppression of the to-be-ignored color was only present in the centrally located RDK but not in the one with the same color in the periphery. This result was at odds with the idea of active suppression of task-irrelevant features across the entire visual field. In the present study, we introduced competition in the periphery by superimposing the RDKs at the task-irrelevant location as well. With such competition, we found suppression of the task-irrelevant color in the centrally and peripherally located RDKs. Results clearly demonstrate that suppression of task-irrelevant features at task-irrelevant locations requires (spatial) competitive interactions and is not an inherent neural mechanism in feature-based attention as was found for global facilitation., (Copyright © 2018. Published by Elsevier Inc.)

This work explores the potential of polymeric micrometer sized devices (microcontainers) as oral drug delivery systems (DDS). Arrays of detachable microcontainers (D-MCs) were fabricated on a sacrificial layer to improve the handling and facilitate the collection of individual D-MCs. A model drug, ketoprofen, was loaded into the microcontainers using supercritical CO 2 impregnation, followed by deposition of an enteric coating to protect the drug from the harsh gastric environment and to provide a fast release in the intestine. In vitro, in vivo and ex vivo studies were performed to assess the viability of the D-MCs as oral DDS. D-MCs improved the relative oral bioavailability by 180% within 4h, and increased the absorption rate by 2.4 times compared to the control. This work represents a significant step forward in the translation of these devices from laboratory to clinic., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Transparent objects require acquisition modalities that are very different from the ones used for objects with more diffuse reflectance properties. Digitizing a scene where objects must be acquired with different modalities requires scene reassembly after reconstruction of the object surfaces. This reassembly of a scene that was picked apart for scanning seems unexplored. We contribute with a multimodal digitization pipeline for scenes that require this step of reassembly. Our pipeline includes measurement of bidirectional reflectance distribution functions and high dynamic range imaging of the lighting environment. This enables pixelwise comparison of photographs of the real scene with renderings of the digital version of the scene. Such quantitative evaluation is useful for verifying acquired material appearance and reconstructed surface geometry, which is an important aspect of digital content creation. It is also useful for identifying and improving issues in the different steps of the pipeline. In this work, we use it to improve reconstruction, apply analysis by synthesis to estimate optical properties, and to develop our method for scene reassembly.

Introduction : Transcranial alternating current stimulation (tACS) is emerging as an interventional tool to modulate different functions of the brain, potentially by interacting with intrinsic ongoing neuronal oscillations. Functionally different intrinsic alpha oscillations are found throughout the cortex. Yet it remains unclear whether tACS is capable of specifically modulating the somatosensory mu-rhythm in amplitude. Objectives : We used tACS to modulate mu-alpha oscillations in amplitude. When compared to sham stimulation we expected a modulation of mu-alpha oscillations but not visual alpha oscillations by tACS. Methods : Individual mu-alpha frequencies were determined in 25 participants. Subsequently, blocks of tACS with individual mu-alpha frequency and sham stimulation were applied over primary somatosensory cortex (SI). Electroencephalogram (EEG) was recorded before and after either stimulation or sham. Modulations of mu-alpha and, for control, visual alpha amplitudes were then compared between tACS and sham. Results : Somatosensory mu-alpha oscillations decreased in amplitude after tACS was applied at participants' individual mu-alpha frequency. No changes in amplitude were observed for sham stimulation. Furthermore, visual alpha oscillations were not affected by tACS or sham, respectively. Conclusion : Our results demonstrate the capability of tACS to specifically modulate the targeted somatosensory mu-rhythm when the tACS frequency is tuned to the individual endogenous rhythm and applied over somatosensory areas. Our results are in contrast to previously reported amplitude increases of visual alpha oscillations induced by tACS applied over visual cortex. Our results may point to a specific interaction between our stimulation protocol and the functional architecture of the somatosensory system.

Low spatial frequency (LSF) image content has been proposed to play a superior functional role in emotional content extraction via the magnocellular pathway biasing attentional resources toward emotional content in visual cortex. We investigated whether emotionally unpleasant complex images that were presented either unfiltered or with LSF content only in the background while subjects performed a foreground task will withdraw more attentional resources from the task compared to unemotional, neutral images (distraction paradigm). We measured steady-state visual evoked potentials (SSVEPs) driven by flickering stimuli of a foreground task. Unfiltered unpleasant images resulted in a significant reduction of SSVEP amplitude compared to neutral images. No statistically significant differences were found with LSF background images. In a behavioral control experiment, we found no significant differences for complexity ratings between unfiltered and LSF pictures. Content identification was possible for unfiltered and LSF picture (correct responses > 74%). An additional EEG study examined typical emotion-related components for complex images presented either as unfiltered, LSF, or high spatial frequency (HSF, as an additional control) filtered, unpleasant, and neutral images. We found a significant main effect of emotional valence in the early posterior negativity. Late positive potential differences were only found for unfiltered and HSF images. Results suggest that, while LSF content is sufficient to allow for content and emotional cue extraction when images were presented alone, LSF content is not salient enough to serve as emotional distractor that withdraws attentional resources from a foreground task in early visual cortex., (© 2016 Society for Psychophysiological Research.)

Transcranial alternating current stimulation (tACS) is a form of noninvasive brain stimulation and is capable of influencing brain oscillations and cortical networks. In humans, the endogenous oscillation frequency in sensorimotor areas peaks at 20 Hz. This beta-band typically occurs during maintenance of tonic motor output and seems to play a role in interhemispheric coordination of movements. Previous studies showed that tACS applied in specific frequency bands over primary motor cortex (M1) or the visual cortex modulates cortical excitability within the stimulated hemisphere. However, the particular impact remains controversial because effects of tACS were shown to be frequency, duration and location specific. Furthermore, the potential of tACS to modulate cortical interhemispheric processing, like interhemispheric inhibition (IHI), remains elusive. Transcranial magnetic stimulation (TMS) is a noninvasive and well-tolerated method of directly activating neurons in superficial areas of the human brain and thereby a useful tool for evaluating the functional state of motor pathways. The aim of the present study was to elucidate the immediate effect of 10 min tACS in the β-frequency band (20 Hz) over left M1 on IHI between M1s in 19 young, healthy, right-handed participants. A series of TMS measurements (motor evoked potential (MEP) size, resting motor threshold (RMT), IHI from left to right M1 and vice versa) was performed before and immediately after tACS or sham using a double-blinded, cross-over design. We did not find any significant tACS-induced modulations of intracortical excitation (as assessed by MEP size and RMT) and/or IHI. These results indicate that 10 min of 20 Hz tACS over left M1 seems incapable of modulating immediate brain activity or inhibition. Further studies are needed to elucidate potential aftereffects of 20 Hz tACS as well as frequency-specific effects of tACS on intracortical excitation and IHI.

Background: Why are weak sensory stimuli sometimes perceived and other times not? Experimental paradigms using near-threshold stimuli suggest that spontaneous brain network dynamics are involved in separating relevant from irrelevant information. Recent findings in human visual perception provide evidence that the immediate spontaneous brain state, i.e. the phase of alpha oscillations, predicts whether a coinciding stimulus is further processed or not., Objectives: Here, we investigated whether this concept of a "pulsed inhibition" involved in sensory gating represents a general mechanism of conscious human perception and can be modulated with non-invasive brain stimulation., Methods: Hence, we used transcranial alternating current stimulation (tACS) at the individualized mu-alpha frequency to entrain somatosensory mu-alpha oscillations, and investigated the effect on somatosensory detection in healthy humans. tACS (or sham, respectively) was applied over primary somatosensory cortices (mu-tACS) while participants performed a detection task of somatosensory near-threshold stimuli., Results: We found that mean perception thresholds during mu-tACS did not change as compared to sham stimulation. However, during mu-tACS, somatosensory detection thresholds varied as a function of the applied tACS phase. This effect was not found when tACS was applied over occipital areas at participant's individual visual alpha frequency., Conclusion: Our data indicate that tACS applied at an endogenous frequency is capable of modulating human somatosensory perception by inducing phase-dependent periods of excitation and inhibition, i.e. entraining ongoing mu-alpha oscillations. These findings support the idea that the "pulsed inhibition" framework for sensory gating applies to somatosensory mu-alpha oscillations and might therefore represent a general, but sensory-specific mechanism of conscious human perception., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Trance is an absorptive state of consciousness characterized by narrowed awareness of external surroundings and has long been used-for example, by shamans-to gain insight. Shamans across cultures often induce trance by listening to rhythmic drumming. Using functional magnetic resonance imaging (fMRI), we examined the brain-network configuration associated with trance. Experienced shamanic practitioners (n = 15) listened to rhythmic drumming, and either entered a trance state or remained in a nontrance state during 8-min scans. We analyzed changes in network connectivity. Trance was associated with higher eigenvector centrality (i.e., stronger hubs) in 3 regions: posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (dACC), and left insula/operculum. Seed-based analysis revealed increased coactivation of the PCC (a default network hub involved in internally oriented cognitive states) with the dACC and insula (control-network regions involved in maintaining relevant neural streams). This coactivation suggests that an internally oriented neural stream was amplified by the modulatory control network. Additionally, during trance, seeds within the auditory pathway were less connected, possibly indicating perceptual decoupling and suppression of the repetitive auditory stimuli. In sum, trance involved coactive default and control networks, and decoupled sensory processing. This network reconfiguration may promote an extended internal train of thought wherein integration and insight can occur., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We present results from the first fully relativistic simulations of the critical collapse of rotating radiation fluids. We observe critical scaling both in subcritical evolutions-in which case the fluid disperses to infinity and leaves behind flat space-and in supercritical evolutions, which lead to the formation of black holes. We measure the mass and angular momentum of these black holes, and find that both show critical scaling with critical exponents that are consistent with perturbative results. The critical exponents are universal: they are not affected by angular momentum, and are independent of the direction in which the critical curve, which separates subcritical from supercritical evolutions in our two-dimensional parameter space, is crossed. In particular, these findings suggest that the angular momentum decreases more rapidly than the square of the mass, so that, as criticality is approached, the collapse leads to the formation of a nonspinning black hole. We also demonstrate excellent agreement of our numerical data with new closed-form extensions of power-law scalings that describe the mass and angular momentum of rotating black holes formed close to criticality.

Objective: The aim of the study was to investigate the effects of facilitatory anodal tDCS (a-tDCS) applied over the leg area of the primary motor cortex on learning a complex whole-body dynamic balancing task (DBT). We hypothesized that a-tDCS during DBT enhances learning performance compared to sham tDCS (s-tDCS)., Methods: In a randomized, parallel design, we applied either a-tDCS (n=13) or s-tDCS (n=13) in a total of 26 young subjects while they perform the DBT. Task performance and error rates were compared between groups. Additionally, we investigated the effect of tDCS on the relationship between performance and kinematic variables capturing different aspects of task execution., Results: A-tDCS over M1 leg area promotes balance performance in a DBT relative to s-tDCS, indicated by higher performance and smaller error scores. Furthermore, a-tDCS seems to mediate the relationship between DBT performance and the kinematic variable velocity., Conclusions: Our findings provide novel evidence for the ability of tDCS to improve dynamic balance learning, a fact, particularly important in the context of treating balance and gait disorders., Significance: TDCS facilitates dynamic balance performance by strengthening the inverse relationship of performance and velocity, thus making tDCS one potential technique to improve walking ability or help to prevent falls in patients in the future., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Perception of illusory contours was shown to be a consequence of neural activity related to spatial integration in early visual areas. Candidates for such filling-in phenomena are long-range horizontal connections of neurons in V1/V2, and feedback from higher order visual areas. To get a direct measure of spatial integration in early visual cortex, we presented two differently flickering inducers, which evoked steady-state visual evoked potentials (SSVEPs) while manipulating the formation of an illusory rectangle. As a neural marker of integration we tested differences in amplitudes of intermodulation frequencies i.e. linear combinations of the driving frequencies. These were significantly increased when an illusory rectangle was perceived. Increases were neither due to changes of any of the two driving frequencies nor in the frequency that tagged the processing of the compound object, indicating that results are not a consequence of paying more attention to inducers when the illusory rectangle was visible., (Copyright © 2013 Elsevier B.V. All rights reserved.)

During simultaneous EEG-fMRI acquisition, the EEG signal suffers from tremendous artifacts caused by the scanner "environment". Particularly, gradient artifacts and the ballistocardiogram have been well characterized, along with methods to eliminate them. Here, we describe another systematic artifact in the EEG signal, which is induced by the internal ventilation system of Siemens TRIO and VERIO MR scanners. A ventilation-level dependent vibration induces specific peaks in the frequency spectrum of the EEG. These frequency peaks are in the range of physiologically relevant brain rhythms (gamma frequency range), and thus interfere with their reliable acquisition. This ventilation dependent artifact was most prominent on the electrodes placed directly on the subject's head, so it is not sufficient to simply place the EEG's amplifier outside the scanner tube. Instead, the ventilator must be switched off to fully eliminate the ventilator's artificial manipulation of EEG recordings. Without the internal ventilator system being on, the temperature within the scanner tube may rise, thus requiring shorter scanning sessions or an additional external ventilation system., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Upconverting nanoparticles (UCNPs) have recently shown great potential as contrast agents in biological applications. In developing different UCNPs, the characterization of their quantum yield (QY) is a crucial issue, as the typically drastic decrease in QY for low excitation power densities can either impose a severe limitation or provide an opportunity in many applications. The power density dependence of the QY is governed by the competition between the energy transfer upconversion (ETU) rate and the linear decay rate in the depopulation of the intermediate state of the involved activator in the upconversion process. Here we show that the QYs of Yb(3+) sensitized two-photon upconversion emissions can be well characterized by the balancing power density, at which the ETU rate and the linear decay rate have equal contributions, and its corresponding QY. The results in this paper provide a method to fully describe the QY of upconverting nanoparticles for arbitrary excitation power densities, and is a fast and simple approach for assessing the applicability of UCNPs from the perspective of energy conversion.

Transcranial direct current stimulation (tDCS) modulates cortical excitability thereby influencing behavior and learning. While previous studies focused on tDCS after-effects, limited information about "online" tDCS effects is available. This in turn is an important prerequisite to better characterize and/or optimize tDCS effects. Here, we aimed to explore the feasibility of recording low-artifact somatosensory evoked potentials (SEPs) during tDCS using a novel ring electrode setup. We recorded SEP before, during and after 10 min of anodal or sham tDCS using a full-band direct current (DC) EEG system in a total number of 3 subjects. SEPs were recorded in the bore of the tDCS ring electrode. Using this approach, no tDCS-induced artifacts could be observed after the application of a standard EEG filter. This new setup might help to better characterize how tDCS alters evoked brain responses thus providing novel insight into underlying physiological effects during stimulation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A key issue regarding the use of stem cells in cardiovascular regenerative medicine is their retention in target tissues. Here, we have generated and assessed a bispecific antibody heterodimer designed to improve the retention of bone-marrow-derived multipotent stromal cells (BMMSC) in cardiac tissue damaged by myocardial infarction. The heterodimer comprises an anti-human CD90 monoclonal antibody (mAb) (clone 5E10) and an anti-myosin light chain 1 (MLC1) mAb (clone MLM508) covalently cross-linked by a bis-arylhydrazone. We modified the anti-CD90 antibody with a pegylated-4-formylbenzamide moiety to a molar substitution ratio (MSR) of 2.6 and the anti-MLC1 antibody with a 6-hydrazinonicotinamide moiety to a MSR of 0.9. The covalent modifications had no significant deleterious effect on mAb epitope binding. Furthermore, the binding of anti-CD90 antibody to BMMSCs did not prevent their differentiation into adipo-, chondro-, or osteogenic lineages. Modified antibodies were combined under mild conditions (room temperature, pH 6, 1 h) in the presence of a catalyst (aniline) to allow for rapid generation of the covalent bis-arylhydrazone, which was monitored at A(354). We evaluated epitope immunoreactivity for each mAb in the construct. Flow cytometry demonstrated binding of the bispecific construct to BMMSCs that was competed by free anti-CD90 mAb, verifying that modification and cross-linking were not detrimental to the anti-CD90 complementarity-determining region. Similarly, ELISA-based assays demonstrated bispecific antibody binding to plastic-immobilized recombinant MLC1. Excess anti-MLC1 mAb competed for bispecific antibody binding. Finally, the anti-CD90 × anti-MLC1 bispecific antibody construct induced BMMSC adhesion to plastic-immobilized MLC1 that was resistant to shear stress, as measured in parallel-plate flow chamber assays. We used mAbs that bind both human antigens and the respective pig homologues. Thus, the anti-CD90 × anti-MLC1 bispecific antibody may be used in large animal studies of acute myocardial infarction and may provide a starting point for clinical studies.

Development of the ARCHITECT Toxo IgM assay has been done to assist the clinician in acute Toxoplasma gondii infection detection, especially in pregnant women. Its use, in conjunction with ARCHITECT Toxo IgG and Toxo Avidity assays, will provide an array of assays particularly useful in the monitoring of pregnant females to determine the risk of maternal transmission of the parasite. Specificity results from 2 testing sites, using populations of pregnant females, hospital patients, and blood donors, demonstrated that the assay has an overall resolved relative specificity of 99.89% (confidence interval, 99.68-99.98%). Relative specificity for pregnant female specimens was 99.95% (n = 2031). Excellent seroconversion sensitivity was observed for the ARCHITECT Toxo IgM assay, which was similar to the Abbott AxSYM Toxo IgM assay (Abbott Laboratories, Abbott Park, IL). In more than 90% of the panels tested, the 1st bleed detected in the serial bleeds was the same for both assays.

As first discovered by Choptuik, the black hole threshold in the space of initial data for general relativity shows both surprising structure and surprising simplicity. Universality, power-law scaling of the black hole mass, and scale echoing have given rise to the term "critical phenomena". They are explained by the existence of exact solutions which are attractors within the black hole threshold, that is, attractors of codimension one in phase space, and which are typically self-similar. Critical phenomena give a natural route from smooth initial data to arbitrarily large curvatures visible from infinity, and are therefore likely to be relevant for cosmic censorship, quantum gravity, astrophysics, and our general understanding of the dynamics of general relativity.

During plastic deformation of metals and alloys, dislocations arrange in ordered patterns. How and when these self-organization processes take place have remained elusive, because in situ observations have not been feasible. We present an x-ray diffraction method that provided data on the dynamics of individual, deeply embedded dislocation structures. During tensile deformation of pure copper, dislocation-free regions were identified. They showed an unexpected intermittent dynamics, for example, appearing and disappearing with proceeding deformation and even displaying transient splitting behavior. Insight into these processes is relevant for an understanding of the strength and work-hardening of deformed materials.

The two domains of the hairpin ribozyme-substrate complex, usually depicted as straight structural elements, must interact with one another in order to form an active conformation. Little is known about the internal geometry of the individual domains in an active docked complex. Using various crosslinking and structural approaches in conjunction with molecular modeling (constraint-satisfaction program MC-SYM), we have investigated the conformation of the substrate-binding domain in the context of the active docked ribozyme-substrate complex. The model generated by MC-SYM showed that the domain is not straight but adopts a bent conformation (D-shaped) in the docked state of the ribozyme, indicating that the two helices bounding the internal loop are closer than was previously assumed. This arrangement rationalizes the observed ability of hairpin ribozymes with a circularized substrate-binding strand to cleave a circular substrate, and provides essential information concerning the organization of the substrate in the active conformation. The internal geometry of the substrate-binding strand places G8 of the substrate-binding strand near the cleavage site, which has allowed us to predict the crucial role played by this nucleotide in the reaction chemistry., (Copyright 2001 Academic Press.)

Objective: To report a case of ethyl alcohol intoxication associated with paclitaxel administration., Case Summary: A patient who received a 3-hour paclitaxel infusion for metastatic breast carcinoma and developed symptoms of acute alcohol intoxication. A blood ethanol concentration drawn at the end of the paclitaxel infusion was 97.8 mg/dL (0.098%)., Discussion: The amount of alcohol contained in paclitaxel is discussed. A review of the literature revealed one patient series where the highest blood alcohol concentration was one-third that seen in our patient., Conclusions: Clinicians should recognize the potential for alcohol intoxication with paclitaxel administration. This is especially pertinent when higher doses are given over a short period of time.