Frequency-domain source localization shows state-dependent diazepam effects in 47-channel EEG

The topic of this study was to evaluate state-dependent effects of diazepam on the frequency characteristics of 47-channel spontaneous EEG maps. A novel method, the FFT-Dipole-Approximation (Lehmann and Michel, 1990), was used to study effects on the strength and the topography of the maps in the different frequency bands. Map topography was characterized by the 3-dimensional location of the equivalent dipole source and map strength was defined as the spatial standard deviation (the Global Field Power) of the maps of each frequency point. The Global Field Power can be considered as a measure of the amount of energy produced by the system, while the source location gives an estimate of the center of gravity of all sources in the brain that were active at a certain frequency. State-dependency was studied by evaluating the drug effects before and after a continuous performance task of 25 min duration. Clear interactions between drug (diazepam vs. placebo) and time after drug intake (before and after the task) were found, especially in the inferior-superior location of the dipole sources. It supports the hypothesis that diazepam, like other drugs, has different effects on brain functions depending on the momentary functional state of the brain. In addition to the drug effects, clearly different source locations and Global Field Power were found for the different frequency bands, replicating earlier reports (Michel et al., 1992).

Affective attitudes to face images associated with intracerebral EEG source location before face viewing

We investigated whether different, personality-related affective attitudes are associated with different brain electric field (EEG) sources before any emotional challenge (stimulus exposure). A 27-channel EEG was recorded in 15 subjects during eyes-closed resting. After recording, subjects rated 32 images of human faces for affective appeal. The subjects in the first (i.e., most negative) and fourth (i.e., most positive) quartile of general affective attitude were further analyzed. The EEG data (mean=25±4.8 s/subject) were subjected to frequency-domain model dipole source analysis (FFT-Dipole-Approximation), resulting in 3-dimensional intracerebral source locations and strengths for the delta–theta, alpha, and beta EEG frequency band, and for the full range (1.5–30 Hz) band. Subjects with negative attitude (compared to those with positive attitude) showed the following source locations: more inferior for all frequency bands, more anterior for the delta–theta band, more posterior and more right for the alpha, beta and 1.5–30 Hz bands. One year later, the subjects were asked to rate the face images again. The rating scores for the same face images were highly correlated for all subjects, and original and retest affective mean attitude was highly correlated across subjects. The present results show that subjects with different affective attitudes to face images had different active, cerebral, neural populations in a task-free condition prior to viewing the images. We conclude that the brain functional state which implements affective attitude towards face images as a personality feature exists without elicitors, as a continuously present, dynamic feature of brain functioning.

Face-elicited ERPs and affective attitude: brain electric microstate and tomography analyses

Objectives: Although behavioral studies have demonstrated that normative affective traits modulate the processing of facial and emotionally charged stimuli, direct electrophysiological evidence for this modulation is still lacking. Methods: Event-related potential (ERP) data associated with personal, traitlike approach- or withdrawal-related attitude (assessed post-recording and 14 months later) were investigated in 18 subjects during task-free (i.e. unrequested, spontaneous) emotional evaluation of faces. Temporal and spatial aspects of 27 channel ERP were analyzed with microstate analysis and low resolution electromagnetic tomography (LORETA), a new method to compute 3 dimensional cortical current density implemented in the Talairach brain atlas. Results: Microstate analysis showed group differences 132-196 and 196-272 ms poststimulus, with right-shifted electric gravity centers for subjects with negative affective attitude. During these (over subjects reliably identifiable) personality-modulated, face-elicited microstates, LORETA revealed activation of bilateral occipito-temporal regions, reportedly associated with facial configuration extraction processes. Negative compared to positive affective attitude showed higher activity right temporal; positive compared to negative attitude showed higher activity left temporo-parieto-occipital. Conclusions: These temporal and spatial aspects suggest that the subject groups differed in brain activity at early, automatic, stimulus-related face processing steps when structural face encoding (configuration extraction) occurs. In sum, the brain functional microstates associated with affect-related personality features modulate brain mechanisms during face processing already at early information processing stages.

Smell and taste of chewing gum affect frequency domain EEG source localizations

We investigated brain electric field signatures of subjective feelings after chewing regular gum or gum base without flavor. 19-channel eyes-closed EEG from 20 healthy males before and after 5 minutes of chewing the two gum types in random sequence was source modeled in the frequency domain using the FFT-Dipole-Approximation. 3-dimensional brain locations and strengths (Global Field Power, GFP) of the equivalent sources of five frequency bands were computed as changes from pre-chewing baseline. Gum types differed (ANOVA) in pre-post changes of source locations for the alpha-2 band (to anterior and right after regular gum, opposite after gum base) and beta-2 band (to anterior and inferior after regular gum, opposite after gum base), and of GFP for delta-theta, alpha-2 and beta-1 (regular gum: increase, gum base: decrease). Subjective feeling changed to more positive values after regular gum than gum base (ANOVA).—Thus, chewing gum with and without taste-smell activates different brain neuronal populations.

Interventions for the management of mandibular fractures

BACKGROUND Fractures of the mandible (lower jaw) are a common occurrence and usually related to interpersonal violence or road traffic accidents. Mandibular fractures may be treated using open (surgical) and closed (non-surgical) techniques. Fracture sites are immobilized with intermaxillary fixation (IMF) or other external or internal devices (i.e. plates and screws) to allow bone healing. Various techniques have been used, however uncertainty exists with respect to the specific indications for each approach. OBJECTIVES The objective of this review is to provide reliable evidence of the effects of any interventions either open (surgical) or closed (non-surgical) that can be used in the management of mandibular fractures, excluding the condyles, in adult patients. SEARCH METHODS We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 28 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE via OVID (1950 to 28 February 2013), EMBASE via OVID (1980 to 28 February 2013), metaRegister of Controlled Trials (to 7 April 2013), ClinicalTrials.gov (to 7 April 2013) and the WHO International Clinical Trials Registry Platform (to 7 April 2013). The reference lists of all trials identified were checked for further studies. There were no restrictions regarding language or date of publication. SELECTION CRITERIA Randomised controlled trials evaluating the management of mandibular fractures without condylar involvement. Any studies that compared different treatment approaches were included. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed trial quality and extracted data. Results were to be expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. Heterogeneity was to be investigated to include both clinical and methodological factors. MAIN RESULTS Twelve studies, assessed as high (six) and unclear (six) risk of bias, comprising 689 participants (830 fractures), were included. Interventions examined different plate materials and morphology; use of one or two lag screws; microplate versus miniplate; early and delayed mobilization; eyelet wires versus Rapid IMF™ and the management of angle fractures with intraoral access alone or combined with a transbuccal approach. Patient-oriented outcomes were largely ignored and post-operative pain scores were inadequately reported. Unfortunately, only one or two trials with small sample sizes were conducted for each comparison and outcome. Our results and conclusions should therefore be interpreted with caution. We were able to pool the results for two comparisons assessing one outcome. Pooled data from two studies comparing two miniplates versus one miniplate revealed no significant difference in the risk of post-operative infection of surgical site (risk ratio (RR) 1.32, 95% CI 0.41 to 4.22, P = 0.64, I(2) = 0%). Similarly, no difference in post-operative infection between the use of two 3-dimensional (3D) and standard (2D) miniplates was determined (RR 1.26, 95% CI 0.19 to 8.13, P = 0.81, I(2) = 27%). The included studies involved a small number of participants with a low number of events. AUTHORS' CONCLUSIONS This review illustrates that there is currently inadequate evidence to support the effectiveness of a single approach in the management of mandibular fractures without condylar involvement. The lack of high quality evidence may be explained by clinical diversity, variability in assessment tools used and difficulty in grading outcomes with existing measurement tools. Until high level evidence is available, treatment decisions should continue to be based on the clinician's prior experience and the individual circumstances.

[Cone beam computed tomography in endodontics: a review for daily clinical practice]

Since the introduction of cone beam computed tomography (CBCT), this 3-dimensional diagnostic imaging technique has been established in a growing number of fields in dental medicine. It has become an important tool for both diagnosis and treatment planning, and is also able to support endodontic treatments. However, the higher effective dose of ionizing radiation compared to conventional 2-dimensional radiographs is not justifiable in every case. CBCT allows for a more precise diagnosis of periapical lesions, root fractures as well as external and internal resorptions. Concerning the utility of CBCT in treatment planning decisions, the gain of information through 3-dimensional imaging for any of these pathologies has to be evaluated carefully on an individual basis. Moreover, radioopaque materials such as root canal filling and posts often create artefacts, which may compromise diagnosis. The aim of this review is to summarize the possibilities and limits of CBCT imaging in endodontology as well as introduce guidelines for daily clinical practice. Furthermore, the article presents possible therapeutic advantages of preexisting CBCT scans for root canal treatments.

Regional myocardial wall thinning at multidetector computed tomography correlates to arrhythmogenic substrate in postinfarction ventricular tachycardia: assessment of structural and electrical substrate

BACKGROUND A majority of patients undergoing ablation of ventricular tachycardia have implanted devices precluding substrate imaging with delayed-enhancement MRI. Contrast-enhanced multidetector computed tomography (MDCT) can depict myocardial wall thickness with submillimetric resolution. We evaluated the relationship between regional myocardial wall thinning (WT) imaged by MDCT and arrhythmogenic substrate in postinfarction ventricular tachycardia. METHODS AND RESULTS We studied 13 consecutive postinfarction patients undergoing MDCT before ablation. MDCT data were integrated with high-density 3-dimensional electroanatomic maps acquired during sinus rhythm (endocardium, 509±291 points/map; epicardium, 716±323 points/map). Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were assessed with regard to the WT. A significant correlation was found between the areas of WT <5 mm and endocardial low voltage (correlation-R=0.82; P=0.001), but no such correlation was found in the epicardium. The WT <5 mm area was smaller than the endocardial low-voltage area (54 cm(2) [Q1-Q3, 46-92] versus 71 cm(2) [Q1-Q3, 59-124]; P=0.001). Among a total of 13 060 electrograms reviewed in the whole study population, 538 LAVA were detected and analyzed. LAVA were located within the WT <5 mm (469/538 [87%]) or at its border (100% within 23 mm). Very late LAVA (>100 ms after QRS complex) were almost exclusively detected within the thinnest area (93% in the WT<3 mm). CONCLUSIONS Regional myocardial WT correlates to low-voltage regions and distribution of LAVA critical for the generation and maintenance of postinfarction ventricular tachycardia. The integration of MDCT WT with 3-dimensional electroanatomic maps can help focus mapping and ablation on the culprit regions, even when MRI is precluded by the presence of implanted devices.

Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial.

OBJECTIVES This study was conducted to determine if an additional procedural endpoint of unexcitability (UE) to pacing along the ablation line reduces recurrence of atrial fibrillation (AF) or atrial tachycardia (AT) after radiofrequency catheter ablation. BACKGROUND AF/AT recurrence is common after pulmonary vein isolation (PVI). METHODS We included 102 patients from 2 centers (age 63 ± 10 years; 33 women; left atrium 38 ± 7 mm; left ventricular ejection fraction 61 ± 6%) with symptomatic paroxysmal AF. A 3-dimensional mapping system and circumferential mapping catheter were used in all patients for PVI. In group 1 (n = 50), the procedural endpoint was bidirectional block across the ablation line. In group 2 (n = 52), additional UE to bipolar pacing at an output of 10 mA and 2-ms pulse width was required. The primary endpoint was freedom from any AF/AT (>30 s) after discontinuation of antiarrhythmic drugs. RESULTS Procedural endpoints were successfully achieved in all patients. Procedure duration was significantly longer in group 2 (185 ± 58 min vs. 139 ± 57 min; p < 0.001); however, fluoroscopy times were not different (23 ± 9 min vs. 23 ± 9 min; p = 0.49). After a follow-up of 12 months in all patients, 26 patients (52%) in group 1 versus 43 (82.7%) in group 2 were free from any AF/AT (p = 0.001) after a single procedure. No major complications occurred. CONCLUSIONS The use of pacing to ensure UE along the PVI line markedly improved near-term single-procedure success, compared with demonstration of bidirectional block alone. This additional endpoint significantly improved patient outcomes after PVI. (Unexcitability Along the Ablation as an Endpoint for Atrial Fibrillation Ablation; NCT01724437).

Quantification of Popliteal Artery Deformation During Leg Flexion in Subjects With Peripheral Artery Disease: A Pilot Study

Purpose: To quantify the in vivo deformations of the popliteal artery during leg flexion in subjects with clinically relevant peripheral artery disease (PAD). Methods: Five patients (4 men; mean age 69 years, range 56–79) with varying calcification levels of the popliteal artery undergoing endovascular revascularization underwent 3-dimensional (3D) rotational angiography. Image acquisition was performed with the leg straight and with a flexion of 70°/20° in the knee/hip joints. The arterial centerline and the corresponding branches in both positions were segmented to create 3D reconstructions of the arterial trees. Axial deformation, twisting, and curvatures were quantified. Furthermore, the relationships between the calcification levels and the deformations were investigated. Results: An average shortening of 5.9%±2.5% and twist rate of 3.8±2.2°/cm in the popliteal artery were observed. Maximal curvatures in the straight and flexed positions were 0.12±0.04 cm−1 and 0.24±0.09 cm−1, respectively. As the severity of calcification increased, the maximal curvature in the straight position increased from 0.08 to 0.17 cm−1, while an increase from 0.17 to 0.39 cm−1 was observed for the flexed position. Axial elongations and arterial twisting were not affected by the calcification levels. Conclusion: The popliteal artery of patients with symptomatic PAD is exposed to significant deformations during flexion of the knee joint. The severity of calcification directly affects curvature, but not arterial length or twisting angles. This pilot study also showed the ability of rotational angiography to quantify the 3D deformations of the popliteal artery in patients with various levels of calcification.

Lifshitz holographic renormalization from anti-de Sitter 1

Lifshitz space–times with critical exponent z = 2 can be obtained by dimensional reduction of Schrödinger space–times with critical exponent z = 0. The latter space–times are asymptotically anti-de Sitter (AdS) solutions of AdS gravity coupled to an axion–dilaton system (or even just a massless scalar field). This basic observation is used to perform holographic renormalization for four-dimensional asymptotically locally Lifshitz space–times by dimensional reduction of the corresponding problem of holographic renormalization for five-dimensional asymptotically AdS space–times coupled to an axion–dilaton system. In this setup the four-dimensional structure of the Lifshitz – Fefferman-Graham expansion and the structure of the counterterm action, including the scale anomaly, will be summarized.

Exploring the validity and reliability of a questionnaire for evaluating virtual patient design with a special emphasis on fostering clinical reasoning

Background: The design of Virtual Patients (VPs) is essential. So far there are no validated evaluation instruments for VP design published. Summary of work: We examined three sources of validity evidence of an instrument to be filled out by students aimed at measuring the quality of VPs with a special emphasis on fostering clinical reasoning: (1) Content was examined based on theory of clinical reasoning and an international VP expert team. (2) Response process was explored in think aloud pilot studies with students and content analysis of free text questions accompanying each item of the instrument. (3) Internal structure was assessed by confirmatory factor analysis (CFA) using 2547 student evaluations and reliability was examined utilizing generalizability analysis. Summary of results: Content analysis was supported by theory underlying Gruppen and Frohna’s clinical reasoning model on which the instrument is based and an international VP expert team. The pilot study and analysis of free text comments supported the validity of the instrument. The CFA indicated that a three factor model comprising 6 items showed a good fit with the data. Alpha coefficients per factor were 0,74 - 0,82. The findings of the generalizability studies indicated that 40-200 student responses are needed in order to obtain reliable data on one VP. Conclusions: The described instrument has the potential to provide faculty with reliable and valid information about VP design. Take-home messages: We present a short instrument which can be of help in evaluating the design of VPs.

Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro-vasopressin-neurophysin II (AVP-NP II).

OBJECTIVE To study clinical, morphological and molecular characteristics in a Swiss family with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). PARTICIPANTS AND METHODS A 15-month-old girl presenting with symptoms of polydipsia and polyuria was investigated by water deprivation test. Evaluation of the family revealed three further family members with symptomatic vasopressin-deficient diabetes insipidus. T1-weighted magnetic resonance images of the posterior pituitary were taken in two affected adult family members and molecular genetic analysis was performed in all affected individuals. RESULTS The water deprivation test in the 15-month-old child confirmed the diagnosis of vasopressin-deficient diabetes insipidus and the pedigree was consistent with autosomal dominant inheritance. The characteristic bright spot of the normal vasopressin-containing neurophypophysis was absent in both adults with adFNDI. Direct sequence analysis revealed a new deletion (177-179DeltaCGC) in exon 2 of the AVP-NP II gene in all affected individuals. At the amino acid level, this deletion eliminates cysteine 59 (C59Delta) and substitutes alanine 60 by tryptophan (A60W) in the AVP-NP II precursor; interestingly, the remainder of the reading frame remains unchanged. According to the three-dimensional structure of neurophysin, C59 is involved in a disulphide bond with C65. CONCLUSIONS Deletion of C59 and substitution of A60W in the AVP-NP II precursor is predicted to disrupt one of the seven disulphide bridges required for correct folding of the neurophysin moiety and thus disturb the function of neurophysin as the vasopressin transport protein. These data are in line with the clinical and morphological findings in the reported family with adFNDI.

Empirical chemosensitivity testing in a spheroid model of ovarian cancer using a microfluidics-based multiplex platform.

The use of biomarkers to infer drug response in patients is being actively pursued, yet significant challenges with this approach, including the complicated interconnection of pathways, have limited its application. Direct empirical testing of tumor sensitivity would arguably provide a more reliable predictive value, although it has garnered little attention largely due to the technical difficulties associated with this approach. We hypothesize that the application of recently developed microtechnologies, coupled to more complex 3-dimensional cell cultures, could provide a model to address some of these issues. As a proof of concept, we developed a microfluidic device where spheroids of the serous epithelial ovarian cancer cell line TOV112D are entrapped and assayed for their chemoresponse to carboplatin and paclitaxel, two therapeutic agents routinely used for the treatment of ovarian cancer. In order to index the chemoresponse, we analyzed the spatiotemporal evolution of the mortality fraction, as judged by vital dyes and confocal microscopy, within spheroids subjected to different drug concentrations and treatment durations inside the microfluidic device. To reflect microenvironment effects, we tested the effect of exogenous extracellular matrix and serum supplementation during spheroid formation on their chemotherapeutic response. Spheroids displayed augmented chemoresistance in comparison to monolayer culturing. This resistance was further increased by the simultaneous presence of both extracellular matrix and high serum concentration during spheroid formation. Following exposure to chemotherapeutics, cell death profiles were not uniform throughout the spheroid. The highest cell death fraction was found at the center of the spheroid and the lowest at the periphery. Collectively, the results demonstrate the validity of the approach, and provide the basis for further investigation of chemotherapeutic responses in ovarian cancer using microfluidics technology. In the future, such microdevices could provide the framework to assay drug sensitivity in a timeframe suitable for clinical decision making.

Characterization of granite matrix porosity and pore-space geometry by in situ and laboratory methods

Most available studies of interconnected matrix porosity of crystalline rocks are based on laboratory investigations; that is, work on samples that have undergone stress relaxation and were affected by drilling and sample preparation. The extrapolation of the results to in situ conditions is therefore associated with considerable uncertainty, and this was the motivation to conduct the ‘in situ Connected Porosity’ experiment at the Grimsel Test Site (Central Swiss Alps). An acrylic resin doped with fluorescent agents was used to impregnate the microporous granitic matrix in situ around an injection borehole, and samples were obtained by overcoring. The 3-D structure of the porespace, represented by microcracks, was studied by U-stage fluorescence microscopy. Petrophysical methods, including the determination of porosity, permeability and P -wave velocity, were also applied. Investigations were conducted both on samples that were impregnated in situ and on non-impregnated samples, so that natural features could be distinguished from artefacts. The investigated deformed granites display complex microcrack populations representing a polyphase deformation at varying conditions. The crack population is dominated by open cleavage cracks in mica and grain boundary cracks. The porosity of non-impregnated samples lies slightly above 1 per cent, which is 2–2.5 times higher than the in situ porosity obtained for impregnated samples. Measurements of seismic velocities (Vp ) on spherical rock samples as a function of confining pressure, spatial direction and water saturation for both non-impregnated and impregnated samples provide further constraints on the distinction between natural and induced crack types. The main conclusions are that (1) an interconnected network of microcracks exists in the whole granitic matrix, irrespective of the distance to ductile and brittle shear zones, and (2) conventional laboratory methods overestimate the matrix porosity. Calculations of contaminant transport through fractured media often rely on matrix diffusion as a retardation mechanism.

Temporal evolution of strut light intensity after implantation of bioresorbable polymeric intracoronary scaffolds in the ABSORB cohort B trial-an application of a new quantitative method based on optical coherence tomography.

BACKGROUND Quantitative light intensity analysis of the strut core by optical coherence tomography (OCT) may enable assessment of changes in the light reflectivity of the bioresorbable polymeric scaffold from polymer to provisional matrix and connective tissues, with full disappearance and integration of the scaffold into the vessel wall. The aim of this report was to describe the methodology and to apply it to serial human OCT images post procedure and at 6, 12, 24 and 36 months in the ABSORB cohort B trial. METHODS AND RESULTS In serial frequency-domain OCT pullbacks, corresponding struts at different time points were identified by 3-dimensional foldout view. The peak and median values of light intensity were measured in the strut core by dedicated software. A total of 303 corresponding struts were serially analyzed at 3 time points. In the sequential analysis, peak light intensity increased gradually in the first 24 months after implantation and reached a plateau (relative difference with respect to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36 months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at 12 months, 75.0% at 24 months, 93.1% at 36 months). CONCLUSIONS Quantitative light intensity analysis by OCT was capable of detecting subtle changes in the bioresorbable strut appearance over time, and could be used to monitor the bioresorption and integration process of polylactide struts.