Use of PET-CT in diagnostic workup of periprosthetic infection of hip and knee joints: significance in detecting additional infectious focus.

INTRODUCTION: The diagnosis and management of periprosthetic knee and hip infections as well as the identification and management of possible additional infectious foci is of great importance for successful therapy. This study analyses the importance of 18F deoxyglucose PET-CT (PET-CT) in the identification of additional infectious focus and subsequent impact on management of periprosthetic infection (PPI). MATERIAL AND METHODS: A retrospective analysis of the clinical data and findings in the period from January 2008 to December 2018 was carried out. One hundred and four patients with in-hospital treatment due to PPI of a hip or knee joint were identified and included in this study. All patients underwent a standardized clinical examination and further surgical and antibiotic therapy. The reevaluation of performed PET-CTs was specifically carried out with regard to the local PPI or detection of secondary foci. RESULTS: PET-CT successfully verified the PPI in 84.2% of the patients. A total of 78 possible additional foci were detected in PET-CT in 56 (53.8%) of the examined patients. Predilection sites for possible secondary foci were joints (42.3%), pulmonary (15.4%), ear-nose-throat (15.4%), spine (11.5%), and the musculocutaneous tissues (11.5%). Fifty-four positive PET-CT findings were confirmed clinically with need of additional adequate treatment. CONCLUSION: PET-CT is a valuable diagnostic tool to confirm periprosthetic joint infection. At the same time, the whole-body PET/CT may detect additional foci of infection with impact on subsequent treatment strategy. PET was of special value in detecting infections at distant locations far from the primary infected joint in significant number. These distant infection locations can be potential cause of a re-infection. This clearly reflects the need of their diagnosis.

InterCarb: A Community Effort to Improve Interlaboratory Standardization of the Carbonate Clumped Isotope Thermometer Using Carbonate Standards.

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth-system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I-CDES) values for Intercarb-Carbon Dioxide Equilibrium Scale.

Proton beam quality enhancement by spectral phase control of a PW-class laser system.

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.

Mirror to measure small angle x-ray scattering signal in high energy density experiments.

Small angle x-ray scattering (SAXS) is a well established technique to detect nanometer scale structures in matter. In a typical setup, this diagnostic uses a detector with a direct line of sight to the scattering target. However, in the harsh environment of high intensity laser interaction, intense secondary radiation and high-energy particles are generated. Such a setup would therefore suffer a significant increase of noise due to this background, which could eventually prevent such measurements. In this paper, we present a novel tool consisting of a mosaic graphite crystal that works as a mirror for the SAXS signal and allows us to position the detector behind appropriate shielding. This paper studies the performance of this mirror both by experiment at the European XFEL (X-Ray Free-Electron Laser Facility) laboratory and by simulations.

Geochemistry of Vein Calcites Hosted in the Troodos Pillow Lavas and Their Implications for the Timing and Physicochemical Environment of Fracturing, Fluid Circulation, and Vein Mineral Growth.

Calcite veins hosted in pillow lavas of the Late Cretaceous Troodos suprasubduction zone ophiolite provide insights into the timing and physicochemical environment of postmagmatic fracturing and fluid circulation through oceanic crust. This study presents rare earth element and yttrium (REE+Y) concentrations, δ13C, δ18O, 87Sr/86Sr, and clumped isotopic (Δ47) compositions of vein calcites in order to investigate their fluid sources, formation temperatures, and precipitation ages. These geochemical data are combined with microtextural analyses. Intersections of 87Sr/86Sr ratios of vein calcites with the Sr isotope seawater curve suggest two distinct calcite veining phases. Major calcite veining within an interval of ~10 Myr after crust formation is characterized by microtextures that point to extensional fracturing related to crack and sealing, host rock brecciation, and advective fluid flow. These vein calcites show REE+Y characteristics, 87Sr/86Sr ratios, and clumped isotopic compositions indicative of precipitation from seawater at <50 °C. Extended fluid residence times intensified fluid-rock interactions and lowered Y/Ho ratios of some blocky vein calcites, whereas crack and sealing resulted in pristine seawater signatures. Low 87Sr/86Sr ratios of localized high-temperature blocky vein calcites point to the involvement of hydrothermal fluids. These calcites show Mn-controlled oscillatory growth zonations that probably developed in a closed system out of equilibrium. Later calcite veining (<75 Ma) may have coincided with rotation and/or uplift of the Troodos ophiolite. Microtextures of these vein calcites indicate fluid diffusion and fracture-independent crystallization pressure-driven veining. Their variably modified seawater signatures resulted from diffusion-related fluid interaction with hydrothermal sediments.

Isolated proton bunch acceleration by a petawatt laser pulse.

Often, the interpretation of experiments concerning the manipulation of the energy distribution of laser-accelerated ion bunches is complicated by the multitude of competing dynamic processes simultaneously contributing to recorded ion signals. Here we demonstrate experimentally the acceleration of a clean proton bunch. This was achieved with a microscopic and three-dimensionally confined near critical density plasma, which evolves from a 1 µm diameter plastic sphere, which is levitated and positioned with micrometer precision in the focus of a Petawatt laser pulse. The emitted proton bunch is reproducibly observed with central energies between 20 and 40 MeV and narrow energy spread (down to 25%) showing almost no low-energetic background. Together with three-dimensional particle-in-cell simulations we track the complete acceleration process, evidencing the transition from organized acceleration to Coulomb repulsion. This reveals limitations of current high power lasers and viable paths to optimize laser-driven ion sources.

Automatic multimodal detection for long-term seizure documentation in epilepsy.

OBJECTIVE: This study investigated sensitivity and false detection rate of a multimodal automatic seizure detection algorithm and the applicability to reduced electrode montages for long-term seizure documentation in epilepsy patients. METHODS: An automatic seizure detection algorithm based on EEG, EMG, and ECG signals was developed. EEG/ECG recordings of 92 patients from two epilepsy monitoring units including 494 seizures were used to assess detection performance. EMG data were extracted by bandpass filtering of EEG signals. Sensitivity and false detection rate were evaluated for each signal modality and for reduced electrode montages. RESULTS: All focal seizures evolving to bilateral tonic-clonic (BTCS, n=50) and 89% of focal seizures (FS, n=139) were detected. Average sensitivity in temporal lobe epilepsy (TLE) patients was 94% and 74% in extratemporal lobe epilepsy (XTLE) patients. Overall detection sensitivity was 86%. Average false detection rate was 12.8 false detections in 24h (FD/24h) for TLE and 22 FD/24h in XTLE patients. Utilization of 8 frontal and temporal electrodes reduced average sensitivity from 86% to 81%. CONCLUSION: Our automatic multimodal seizure detection algorithm shows high sensitivity with full and reduced electrode montages. SIGNIFICANCE: Evaluation of different signal modalities and electrode montages paces the way for semi-automatic seizure documentation systems.

Relativistic Electron Streaming Instabilities Modulate Proton Beams Accelerated in Laser-Plasma Interactions.

We report experimental evidence that multi-MeV protons accelerated in relativistic laser-plasma interactions are modulated by strong filamentary electromagnetic fields. Modulations are observed when a preplasma is developed on the rear side of a µm-scale solid-density hydrogen target. Under such conditions, electromagnetic fields are amplified by the relativistic electron Weibel instability and are maximized at the critical density region of the target. The analysis of the spatial profile of the protons indicates the generation of B>10 MG and E>0.1 MV/µm fields with a µm-scale wavelength. These results are in good agreement with three-dimensional particle-in-cell simulations and analytical estimates, which further confirm that this process is dominant for different target materials provided that a preplasma is formed on the rear side with scale length ≳0.13λ_{0}sqrt[a_{0}]. These findings impose important constraints on the preplasma levels required for high-quality proton acceleration for multipurpose applications.

Automatic detection of rhythmic and periodic patterns in critical care EEG based on American Clinical Neurophysiology Society (ACNS) standardized terminology.

AIMS OF THE STUDY: Continuous EEG from critical care patients needs to be evaluated time efficiently to maximize the treatment effect. A computational method will be presented that detects rhythmic and periodic patterns according to the critical care EEG terminology (CCET) of the American Clinical Neurophysiology Society (ACNS). The aim is to show that these detected patterns support EEG experts in writing neurophysiological reports. MATERIALS AND METHODS: First of all, three case reports exemplify the evaluation procedure using graphically presented detections. Second, 187 hours of EEG from 10 critical care patients were used in a comparative trial study. For each patient the result of a review session using the EEG and the visualized pattern detections was compared to the original neurophysiology report. RESULTS: In three out of five patients with reported seizures, all seizures were reported correctly. In two patients, several subtle clinical seizures with unclear EEG correlation were missed. Lateralized periodic patterns (LPD) were correctly found in 2/2 patients and EEG slowing was correctly found in 7/9 patients. In 8/10 patients, additional EEG features were found including LPDs, EEG slowing, and seizures. CONCLUSION: The use of automatic pattern detection will assist in review of EEG and increase efficiency. The implementation of bedside surveillance devices using our detection algorithm appears to be feasible and remains to be confirmed in further multicenter studies.

Prospective assessment and validation of rhythmic and periodic pattern detection in NeuroTrend: A new approach for screening continuous EEG in the intensive care unit.

BACKGROUND: NeuroTrend is a computational method that analyzes long-term scalp EEGs in the ICU according to ACNS standardized critical care EEG terminology (CCET) including electrographic seizures. At present, it attempts to become a screening aid for continuous EEG (cEEG) recordings in the ICU to facilitate the review process and optimize resources. METHODS: A prospective multicenter study was performed in two neurological ICUs including 68 patients who were subjected to video-cEEG. Two reviewers independently annotated the first minute of each hour in the cEEG according to CCET. These segments were also screened for faster patterns with frequencies higher than 4 Hz. The matching annotations (2911 segments) were then used as gold standard condition to test sensitivity and specificity of the rhythmic and periodic pattern detection of NeuroTrend. RESULTS: Interrater agreement showed substantial agreement for localization (main term 1) and pattern type (main term 2) of the CCET. The overall detection sensitivity of NeuroTrend was 94% with high detection rates for periodic discharges (PD = 80%) and rhythmic delta activity (RDA = 82%). Overall specificity was moderate (67%) mainly because of false positive detections of RDA in cases of general slowing. In contrast, a detection specificity of 88% for PDs was reached. Localization revealed only a slight agreement between reviewers and NeuroTrend. CONCLUSIONS: NeuroTrend might be a suitable screening tool for cEEG in the ICU and has the potential to raise efficiency of long-term EEG monitoring in the ICU. At this stage, pattern localization and differentiation between RDA and general slowing need improvement. This article is part of a Special Issue entitled "Status Epilepticus".

Prediction of rhythmic and periodic EEG patterns and seizures on continuous EEG with early epileptiform discharges.

BACKGROUND: Continuous EEG (cEEG) is necessary to document nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), as well as rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' (RPPIIU) including periodic discharges, rhythmic delta activity, and spike-and-wave complexes in neurological intensive care patients. However, cEEG is associated with significant recording and analysis efforts. Therefore, predictors from short-term routine EEG with a reasonably high yield are urgently needed in order to select patients for evaluation with cEEG. OBJECTIVE: The aim of this study was to assess the prognostic significance of early epileptiform discharges (i.e., within the first 30 min of EEG recording) on the following: (1) incidence of ictal EEG patterns and RPPIIU on subsequent cEEG, (2) occurrence of acute convulsive seizures during the ICU stay, and (3) functional outcome after 6 months of follow-up. METHODS: We conducted a separate analysis of the first 30 min and the remaining segments of prospective cEEG recordings according to the ACNS Standardized Critical Care EEG Terminology as well as NCS criteria and review of clinical data of 32 neurological critical care patients. RESULTS: In 17 patients with epileptiform discharges within the first 30 min of EEG (group 1), electrographic seizures were observed in 23.5% (n = 4), rhythmic or periodic EEG patterns of 'ictal-interictal uncertainty' in 64.7% (n = 11), and neither electrographic seizures nor RPPIIU in 11.8% (n = 2). In 15 patients with no epileptiform discharges in the first 30 min of EEG (group 2), no electrographic seizures were recorded on subsequent cEEG, RPPIIU were seen in 26.7% (n = 4), and neither electrographic seizures nor RPPIIU in 73.3% (n = 11). The incidence of EEG patterns on cEEG was significantly different between the two groups (p = 0.008). Patients with early epileptiform discharges developed acute seizures more frequently than patients without early epileptiform discharges (p = 0.009). Finally, functional outcome six months after discharge was significantly worse in patients with early epileptiform discharges (p=0.01). CONCLUSIONS: Epileptiform discharges within the first 30 min of EEG recording are predictive for the occurrence of ictal EEG patterns and for RPPIIU on subsequent cEEG, for acute convulsive seizures during the ICU stay, and for a worse functional outcome after 6 months of follow-up. This article is part of a Special Issue entitled Status Epilepticus.

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

OBJECTIVE: A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. METHODS: A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. RESULTS: A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. CONCLUSIONS: The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. SIGNIFICANCE: The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients.

PureEEG: automatic EEG artifact removal for epilepsy monitoring.

AIM OF THE STUDY: A novel method for removal of artifacts from long-term EEGs was developed and evaluated. The method targets most types of artifacts and works without user interaction. MATERIALS AND METHODS: The method is based on a neurophysiological model and utilizes an iterative Bayesian estimation scheme. The performance was evaluated by two independent reviewers. From 48 consecutive epilepsy patients, 102 twenty-second seizure onset EEGs were used to evaluate artifacts before and after artifact removal and regarding the erroneous attenuation of true EEG patterns. RESULTS: The two reviewers found "major improvements" in 59% and 49% of the EEG epochs respectively, and "minor improvements" in 38% and 47% of the epochs, respectively. The answer "similar or worse" was chosen only in 0% and 4%, respectively. Neither of the reviewers found "major attenuations", i.e., a significant attenuation of significant EEG patterns. Most EEG epochs were found to be either "mostly preserved" or "all preserved". A "minor attenuation" was found only in 0% and 17%, respectively. CONCLUSIONS: The proposed artifact removal algorithm effectively removes artifacts from EEGs and improves the readability of EEGs impaired by artifacts. Only in rare cases did the algorithm slightly attenuate EEG patterns, but the clear visibility of significant patterns was preserved in all cases of this study. Current artifact removal methods work either semi-automatically or with insufficient reliability for clinical use, whereas the "PureEEG" method works fully automatically and leaves true EEG patterns unchanged with a high reliability.

Automatic optimization of parameters for seizure detection systems.

A parameter optimization method for an automatic seizure detection algorithm using the Nelder Mead algorithm is presented. A suitable cost function for joint optimization of sensitivity and false alarm rate is proposed. The optimization is done using EEG datasets from 23 patients and validated on datasets from another 23 patients. The resulting sensitivity was 82.3% with a false alarm rate of 0.24 FA/h. This is a reduction of the false alarm rate by 1.58 FA/h with an acceptable loss of sensitivity of 4.3%.

A novel method for the identification of synchronization effects in multichannel ECoG with an application to epilepsy.

In this paper, we present a novel method for the identification of synchronization effects in multichannel electrocorticograms (ECoG). Based on autoregressive modeling, we define a dependency measure termed extrinsic-to-intrinsic power ratio (EIPR) which quantifies directed coupling effects in the time domain. Hereby, a dynamic input channel selection algorithm assures the estimation of the model parameters despite the strong spatial correlation among the high number of involved ECoG channels. We compare EIPR to the partial directed coherence, show its ability to indicate Granger causality and successfully validate a signal model. Applying EIPR to ictal ECoG data of patients suffering from temporal lobe epilepsy allows us to identify the electrodes of the seizure onset zone. The results obtained by the proposed method are in good accordance with the clinical findings.

Direct observation of prompt pre-thermal laser ion sheath acceleration.

High-intensity laser plasma-based ion accelerators provide unsurpassed field gradients in the megavolt-per-micrometer range. They represent promising candidates for next-generation applications such as ion beam cancer therapy in compact facilities. The weak scaling of maximum ion energies with the square-root of the laser intensity, established for large sub-picosecond class laser systems, motivates the search for more efficient acceleration processes. Here we demonstrate that for ultrashort (pulse duration ~30 fs) highly relativistic (intensity ~10(21) W cm(-2)) laser pulses, the intra-pulse phase of the proton acceleration process becomes relevant, yielding maximum energies of around 20 MeV. Prominent non-target-normal emission of energetic protons, reflecting an engineered asymmetry in the field distribution of promptly accelerated electrons, is used to identify this pre-thermal phase of the acceleration. The relevant timescale reveals the underlying physics leading to the near-linear intensity scaling observed for 100 TW class table-top laser systems.

Combining time series and frequency domain analysis for a automatic seizure detection.

The detection of epileptic seizures in long-term electroencephalographic (EEG) recordings is a time-consuming and tedious task requiring specially trained medical experts. The EpiScan seizure detection algorithm developed by the Austrian Institute of Technology (AIT) has proven to achieve high detection performance with a robust false alarm rate in the clinical setting. This paper introduces a novel time domain method for detection of epileptic seizure patterns with focus on irregular and distorted rhythmic activity. The method scans the EEG for sequences of similar epileptiform discharges and uses a combination of duration and similarity measure to decide for a seizure. The resulting method was tested on an EEG database with 275 patients including over 22000h of unselected and uncut EEG recording and 623 seizures. Used in combination with the EpiScan algorithm we increased the overall sensitivity from 70% to 73% while reducing the false alarm rate from 0.33 to 0.30 alarms per hour.

Automatic seizure detection based on the activity of a set of current dipoles: first steps.

In this paper we show advantages of using an advanced montage scheme with respect to the performance of automatic seizure detection systems. The main goal is to find the best performing montage scheme for our automatic seizure detection system. The new virtual montage is a fix set of dipoles within the brain. The current density signals for these dipoles are derived from the scalp EEG signals based on a smart linear transformation. The reason for testing an alternative approach is that traditional montages (reference, bipolar) have some limitations, e.g. the detection performance depends on the choice of the reference electrode and an extraction of spatial information is often demanding. In this paper we explain the detailed setup of how to adapt a modern seizure detection system to use current density signals. Furthermore, we show results concerning the detection performance of different montage schemes and their combination.

Electron temperature scaling in laser interaction with solids.

A precise knowledge of the temperature and number of hot electrons generated in the interaction of short-pulse high-intensity lasers with solids is crucial for harnessing the energy of a laser pulse in applications such as laser-driven ion acceleration or fast ignition. Nevertheless, present scaling laws tend to overestimate the hot electron temperature when compared to experiment and simulations. We present a novel approach that is based on a weighted average of the kinetic energy of an ensemble of electrons. We find that the scaling of electron energy with laser intensity can be derived from a general Lorentz invariant electron distribution ansatz that does not rely on a specific model of energy absorption. The scaling derived is in perfect agreement with simulation results and clearly follows the trend seen in recent experiments, especially at high laser intensities where other scalings fail to describe the simulations accurately.