Endothelial receptor proteins in acute venous thrombosis and delayed thrombus resolution in cerebral sinus vein thrombosis.

BACKGROUND AND PURPOSE: Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. METHODS: In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. RESULTS: Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer (p < 0.001) and sPECAM-1 (p < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). CONCLUSION: sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.

Phase offset method of ptychographic contrast reversal correction.

The contrast transfer function of direct ptychography methods such as the single side band (SSB) method are single signed, yet these methods still sometimes exhibit contrast reversals, most often where the projected potentials are strong. In thicker samples central focusing often provides the best ptychographic contrast as this leads to defocus variations within the sample canceling out. However focusing away from the entrance surface is often undesirable as this degrades the annular dark field (ADF) signal. Here we discuss how phase wrap asymptotes in the frequency response of SSB ptychography give rise to contrast reversals, without the need for dynamical scattering, and how these can be counteracted by manipulating the phases such that the asymptotes are either shifted to higher frequencies or damped via amplitude modulation. This is what enables post collection defocus correction of contrast reversals. However, the phase offset method of counteracting contrast reversals we introduce here is generally found to be superior to post collection application of defocus, with greater reliability and generally stronger contrast. Importantly, the phase offset method also works for thin and thick samples where central focusing does not. Finally, the independence of the method from focus is useful for optical sectioning involving ptychography, improving interpretability by better disentangling the effects of strong potentials and focus.

Whole-Body Electrostatic Pain Treatment in Adults with Chronic Pain: A Prospective Multicentric Observational Clinical Trial.

INTRODUCTION: In the treatment of patients with chronic pain, whole-body electrostatic therapy using the Elosan Cabin C1 has been proposed as an adjunctive therapy. So far, data on the use of this cabin are limited. Promising results with a significant reduction in pain scores have been obtained in a small group of patients. However, treatment with Elosan Cabin C1 has not been the subject of evaluation in a larger patient population. The aim of this study was to investigate the efficacy and adverse effects of electrostatic treatment in such a population. METHODS: Prospective, multi-center, observational clinical trial conducted in daily practice in a large adult ambulatory population with chronic pain. Each patient received eight weekly Elosan C1 treatment sessions for up to 9 weeks. Treatment was added to an established conservative pain management. Pain scores (visual analog scale (VAS) 0-100, primary outcome) and sleep quality (seven-point Likert scale, secondary outcome) were assessed before, during, and at the end of the treatment period; quality of life (SF-12: Physical Component Summary = PCS, Mental Component Summary = MCS; secondary outcome) was assessed before and at the end of the treatment period. Subgroup analyses were performed for sex, age, duration of pain, initial pain location, pain entity, and pain medication at the start of treatment. RESULTS: A total of 192 patients were enrolled, 143 patients (74.5%) had a complete set of 8 treatment sessions. A reduction in pain scores from 68 ± 14 points to 47 ± 22 points was observed (p < 0.001), 65% of patients (responders) had a reduction of > 15 points. Female patients had a significantly better response than male patients with a higher number of responders (76% vs. 38%; p < 0.001). Patients with a pain history < 1 year had a significantly better response than patients with a pain history > 1 year. The Physical Component Summary (PCS) increased from 36 ± 11 to 41 ± 11 (+ 18%, p < 0.001) and the Mental Component Summary (MCS) from 41 ± 7 to 43 ± 7 (+ 6%, p = 0.3). Overall sleep quality improved significantly from 4.6 ± 1.7 to 3.73 ± 1.7 points (p < 0.001), with a higher proportion of responders in the female group (37 vs. 18%; p < 0.034). No serious adverse events were observed during treatment. CONCLUSIONS: Electrostatic therapy with Elosan Cabin C1 may be a useful and effective adjunct therapy for patients with chronic pain. The results suggest that female patients and those with a recent history of pain experience the greatest benefit. TRIAL REGISTRATION: NCT04818294 (clinicaltrials.gov).

Electrostatic treatment with the Elosan Cabin C1 is a form of pain therapy that works by applying an electrical charge to the outside of the whole body without a corresponding current flowing inside. The treatment is painless and lasts 8 min per session. The study investigated the effect of the Elosan treatment in 143 patients over a period of 8 weeks with sessions once per week. Investigated outcomes were changes in pain, quality of life, sleep quality, and side effects of the treatment. 65% of the patients had a relevant improvement in pain levels, the average pain reduction in all patients was 30.9%. Quality of life and sleep quality also improved significantly. There were no relevant side effects of the treatment. The best effect was seen in female patients and if the duration of pain was less than 1 year. It was found that by applying the electrostatic field once a week, various types of pain can be reduced with a long-lasting effect. The treatment is ideally combined with physiotherapy and other complementary pain therapies.

Reliable phase quantification in focused probe electron ptychography of thin materials.

Electron ptychography provides highly sensitive, dose efficient phase images which can be corrected for aberrations after the data has been acquired. This is crucial when very precise quantification is required, such as with sensitivity to charge transfer due to bonding. Drift can now be essentially eliminated as a major impediment to focused probe ptychography, which benefits from the availability of easily interpretable simultaneous Z-contrast imaging. However challenges have remained when quantifying the ptychographic phases of atomic sites. The phase response of a single atom has a negative halo which can cause atoms to reduce in phase when brought closer together. When unaccounted for, as in integrating methods of quantification, this effect can completely obscure the effects of charge transfer. Here we provide a new method of quantification that overcomes this challenge, at least for 2D materials, and is robust to experimental parameters such as noise, sample tilt.

Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects, the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse.

Micronuclei are DNA-containing structures separate from the nucleus found in cancer cells. Micronuclei are recognized by the immune sensor axis cGAS/STING, driving cancer metastasis. The mitochondrial apoptosis apparatus can be experimentally triggered to a non-apoptotic level, and this can drive the appearance of micronuclei through the Caspase-activated DNAse (CAD). We tested whether spontaneously appearing micronuclei in cancer cells are linked to sub-lethal apoptotic signals. Inhibition of mitochondrial apoptosis or of CAD reduced the number of micronuclei in tumor cell lines as well as the number of chromosomal misalignments in tumor cells and intestinal organoids. Blockade of mitochondrial apoptosis or deletion of CAD reduced, while experimental activation CAD, STING-dependently, enhanced aggressive growth of tumor cells in vitro. Deletion of CAD from human cancer cells reduced metastasis in xenograft models. CAD-deficient cells displayed a substantially altered gene-expression profile, and a CAD-associated gene expression 'signature' strongly predicted survival in cancer patients. Thus, low-level activity in the mitochondrial apoptosis apparatus operates through CAD-dependent gene-induction and STING-activation and has substantial impact on metastasis in cancer.

Aligned Stacking of Nanopatterned 2D Materials for High-Resolution 3D Device Fabrication.

Two-dimensional materials can be combined by placing individual layers on top of each other, so that they are bound only by their van der Waals interaction. The sequence of layers can be chosen arbitrarily, enabling an essentially atomic-level control of the material and thereby a wide choice of properties along one dimension. However, simultaneous control over the structure in the in-plane directions is so far still rather limited. Here, we combine spatially controlled modifications of 2D materials, using focused electron irradiation or electron beam induced etching, with the layer-by-layer assembly of van der Waals heterostructures. The presented assembly process makes it possible to structure each layer with an arbitrary pattern prior to the assembly into the heterostructure. Moreover, it enables a stacking of the layers with accurate lateral alignment, with an accuracy of currently 10 nm, under observation in an electron microscope. Together, this enables the fabrication of almost arbitrary 3D structures with highest spatial resolution.

What sports activity levels can be achieved in the long-term after major lower extremity amputation for malignant tumors? - A minimum follow-up of twenty years.

BACKGROUND: It is well-known that exercise through sports and physical activity has beneficial effects on health. After lower extremity amputation, low rates of participation in sports activities have been shown. So far, there is only limited scientific long-term information concerning sports activity and feasible types of sports in patients with lower extremity amputations due to malignant tumors. This study sought to provide very long-term information about the following questions: (1) What sports activity levels can be achieved after lower extremity amputation due to a malignant tumor? (2) What are feasible types of sports? (3) Is the University of California Los Angeles (UCLA) Activity Score influenced by patient's age, the age at the time of surgery and the amount of prosthesis sockets used to date? HYPOTHESIS: Patients with lower extremity amputation due to a malignant tumor cannot regularly participate in moderate sports activities (UCLA Activity Score≥6) in the very long-term. MATERIALS AND METHODS: In a retrospective questionnaire survey, 21 former patients (seven females, 14 males; median age: 60.5years [range: 33-74]) who underwent an amputation of the lower extremity (14 transfemoral, four knee disarticulations, three transtibial) from 1961 to 1993 due to a malignant tumor were interviewed. The median follow-up was 41.1years (range: 23-55). The patients were interviewed about types of sports, frequencies and durations of sports sessions at the time of the last follow-up, as well as retrospectively. Sports activity levels were then assessed based on the UCLA Activity Score. Demographic background, data on amputation level, histological results, prosthetic devices and revision surgeries were collected. RESULTS: Seven patients (33%) were still regularly exercising at least moderate sports activities at the last follow-up, including one patient regularly participating in impact sports. The preoperative median UCLA Activity Score of 9 (range: 2-10) decreased to 5 (range: 2-10) at the last follow-up (p<0.001). Swimming (13 patients, seven on a regular basis), cycling (seven), downhill skiing (five) and hiking (four) were among the most common feasible types of sports. Increasing age had a negative influence on the UCLA Activity Score [95% CI (-0.034, -0.006); RB=-0.020; SD=0.0074; p=0.007]. CONCLUSION: After a major amputation in the lower extremity due to a malignant tumor, high activity levels by practicing types of sports such as downhill skiing, are achievable. In the very long-term, a regular participation in at least moderate activities, such as swimming, is possible. Programs for physical and sports activities, based on recommendations drawn from long-term experience, are necessary and should be individually tailored to amputees and their limitations. LEVEL OF EVIDENCE: IV.

Toward Exotic Layered Materials: 2D Cuprous Iodide.

Heterostructures composed of 2D materials are already opening many new possibilities in such fields of technology as electronics and magnonics, but far more could be achieved if the number and diversity of 2D materials were increased. So far, only a few dozen 2D crystals have been extracted from materials that exhibit a layered phase in ambient conditions, omitting entirely the large number of layered materials that may exist at other temperatures and pressures. This work demonstrates how such structures can be stabilized in 2D van der Waals (vdw) stacks under room temperature via growing them directly in graphene encapsulation by using graphene oxide as the template material. Specifically, an ambient stable 2D structure of copper and iodine, a material that normally only occurs in layered form at elevated temperatures between 645 and 675 K, is produced. The results establish a simple route to the production of more exotic phases of materials that would otherwise be difficult or impossible to stabilize for experiments in ambient.

Discontinuous Galerkin isogeometric analysis for segmentations generating overlapping regions.

In the Isogeometric Analysis (IGA) framework, the computational domain has very often a multipatch representation. The multipatch domain can be obtained by a volume segmentation of a boundary represented domain, e.g. provided by a Computer Aided Design model. Typically, small gaps and overlapping regions can appear at the patch interfaces of such multipatch representations. In the current work, we consider multipatch representations having only small overlapping regions between the patches. We develop a Discontinuous Galerkin (DG)-IGA method that can be immediately applied to these representations. Our method appropriately connects the fluxes of the one face of the overlapping region with the flux of the opposite face. We provide a theoretical justification of our approach by splitting the whole error into two components: the first is related to the incorrect representation of the patches (consistency error) and the second to the approximation properties of the IGA space. We show bounds for both components of the error. We verify the theoretical error estimates in a series of numerical examples.

Atom-by-atom chemical identification from scanning transmission electron microscopy images in presence of noise and residual aberrations.

The simple dependence of the intensity in annular dark field scanning transmission electron microscopy images on the atomic number provides (to some extent) chemical information about the sample, and even allows an elemental identification in the case of light-element single-layer samples. However, the intensity of individual atoms and atomic columns is affected by residual aberrations and the confidence of an identification is limited by the available signal to noise. Here, we show that matching a simulation to an experimental image by iterative optimization provides a reliable analysis of atomic intensities even in presence of residual non-round aberrations. We compare our new method with other established approaches demonstrating its high reliability for images recorded at limited dose and with different aberrations. This is of particular relevance for analyzing moderately beam-sensitive materials, such as most 2D materials, where the limited sample stability often makes it difficult to obtain spectroscopic information at atomic resolution.

Cross-cultural adaption, translation and validation of the Toronto extremity salvage score (TESS) for patients in German-speaking countries.

OBJECTIVE: The preferred treatment for malignant bone and soft tissue tumors is limb salvage surgery; the Toronto extremity salvage score (TESS) is commonly used to measure physical functioning of the affected extremity. The aims of this study were to translate and culturally adapt the German version of the TESS, as well as to explore its convergent reliability, validity and re-test reliability. STUDY DESIGN: Patients (n = 50) 32 lower extremity (LE) and 18 upper extremity (UE) were asked to fill out the German TESS two times (t1: clinical visit, t2: regular email) and the SF-36 once. METHODS: The TESS questionnaires were translated from English into German, back translated into English, and culturally adapted. The reliability was assessed with Cronbach's alpha (α). The validity was measured with the SF-36 physical component score and TESS using the Spearman rank correlation coefficient (r). Furthermore, the test-retest reliability was calculated with the intraclass correlation coefficient (ICC). RESULTS: Internal consistency for both questionnaires was excellent (LE t1: α = 0.924, t2: α = 0.952; UE t1: α = 0.957, t2: α = 0.898). A statistically significant correlation was found between the SF-36 physical component scale and the German TESS (LE r = 0.741, UE r = 0.713). The ICC between baseline (t1) and re-test (t2) was 0.952 and 0.871 for the lower and upper extremities, respectively. CONCLUSION: Initial evidence demonstrated that the German TESS is a valid and reliable instrument for use with patients after surgical treatment of malignant bone or soft tissue sarcoma.

How Common Are Chronic Residual Limb Pain, Phantom Pain, and Back Pain More Than 20 Years After Lower Limb Amputation for Malignant Tumors?

BACKGROUND: After major lower limb amputation, persistent pain is common, with up to 85% of patients reporting recurring phantom or residual-limb pain. Although pain management is an important factor of quality of life in patients with lower limb amputations, there are few long-term data regarding the frequency of persistent pain and how it impacts prosthesis use. QUESTIONS/PURPOSES: (1) How prevalent are different types of pain at long-term follow-up after amputation for malignant tumors? (2) What association do different pain types have with daily prosthesis use? METHODS: Between 1961 and 1995, 124 major amputations for malignant tumors were performed at one center in Austria in patients (1) who spoke German and (2) whose surgical date resulted in the possibility of a minimum follow-up time of 20 years at the time of this survey; those patients were considered potentially eligible for this retrospective study. The indications for major amputation were to achieve local tumor control in limbs that the surgeon deemed unsalvageable without amputation. Of those 124 patients, 71% (88) had died, 9% (11) could not be reached, and 3% (4) declined to participate. Thus, 58% (21 of 36) of those living at the time of this study and who underwent lower limb amputation between 1961 and 1993 with a median (range) follow-up duration of 41 years (23 to 55) completed a standardized questionnaire, including an assessment of pain and daily prosthesis use during the year before the survey. Phantom pain, residual limb pain, and back pain were each further subclassified into pain frequency, intensity, and restrictions in activities of daily living (ADL) due to the specific pain form and rated on a 5- (pain frequency) and 10-point (pain intensity, restrictions in ADL) numerical rating scale. Before multivariate regression analysis, daily prosthesis use was correlated with pain parameters using Spearman correlation testing. RESULTS: Seventeen of 21 patients reported phantom limb and back pain, and 15 patients reported residual limb pain in the past year. Median (range) phantom pain intensity was 7 (1 to 10) points, median residual limb pain intensity was 4 (1 to 9) points, and median back pain intensity was 5 (1 to 10) points. After controlling for relevant confounding variables such as age at amputation, age at survey, and stump length, we found that less intense residual limb pain (defined on a 10-point scale with 1 representing no pain at all and 10 representing extremely strong pain [95% CI 0.3 to 1.0]; r = 0.8; p = 0.003) was associated with greater daily prosthesis use. Higher amputation levels showed a decreased daily prosthesis use compared with patients with lower amputation levels (defined as transfemoral amputation versus knee disarticulation versus transtibial amputation [95% CI 0.3 to 5.1]; r = 0.5; p = 0.03). CONCLUSION: Decades after surgery, many patients with lower limb amputations experience pain that restricts them in terms of ADLs and decreases their daily prosthesis use. This information supports the need for regular residual limb inspections and careful prosthesis fitting even at long-term follow-up, as effective prosthesis fitting is a modifiable cause of residual limb pain. Future studies evaluating long-term treatment effects of pain relief surgery and therapeutic alternatives to conservative pain treatments should be performed, as these approaches may help alleviate pain in patients with refractory postamputation pain. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Analysis of anaesthesia services to calculate national need and supply of anaesthetics in Switzerland during the COVID-19 pandemic.

BACKGROUND: In Switzerland, details of current anaesthesia practice are unknown. However, they are urgently needed to manage anaesthesia drug supply in times of drug shortages due to the pandemic. METHODS: We surveyed all Swiss anaesthesia institutions in April 2020 to determine their annual anaesthesia activity. Together with a detailed analysis on anaesthetic drug use of a large, representative Swiss anaesthesia index institution, calculations and projections for the annual need of anaesthetics in Switzerland were made. Only those drugs have been analysed that are either being used very frequently or that have been classified critical with regard to their supply by the pharmacy of the index institution or the Swiss Federal Office of Public Health. RESULTS: The response rate to our questionnaire was 98%. Out of the present 188 Swiss anaesthesia institutions, 185 responded. In Switzerland, the annual number of anaesthesias was 1'071'054 (12'445 per 100'000 inhabitants) with a mean anaesthesia time of 2.03 hours. Teaching hospitals (n = 54) performed more than half (n = 572'231) and non-teaching hospitals (n = 103) provided almost half of all anaesthesias (n = 412'531). Thereby, private hospitals conducted a total of 290'690 anaesthesias. Finally, office-based anaesthesia institutions with mainly outpatients (n = 31) administered 86'292 anaesthesias. Regarding type of anaesthesia provided, two thirds were general anaesthesias (42% total intravenous, 17% inhalation, 8% combined), 20% regional and 12% monitored anaesthesia care. Projecting for example the annual need for propofol in anaesthesia, Switzerland requires 48'573 L of propofol 1% which corresponds to 5'644 L propofol 1% per 100'000 inhabitants every year. CONCLUSIONS: To actively manage anaesthesia drug supply in the context of the current pandemic, it is mandatory to have a detailed understanding of the number and types of anaesthesias provided. On this basis, the Swiss annual consumption of anaesthetics could be projected and the replenishment organized.

Radiative lifetime-encoded unicolour security tags using perovskite nanocrystals.

Traditional fluorescence-based tags, used for anticounterfeiting, rely on primitive pattern matching and visual identification; additional covert security features such as fluorescent lifetime or pattern masking are advantageous if fraud is to be deterred. Herein, we present an electrohydrodynamically printed unicolour multi-fluorescent-lifetime security tag system composed of lifetime-tunable lead-halide perovskite nanocrystals that can be deciphered with both existing time-correlated single-photon counting fluorescence-lifetime imaging microscopy and a novel time-of-flight prototype. We find that unicolour or matching emission wavelength materials can be prepared through cation-engineering with the partial substitution of formamidinium for ethylenediammonium to generate "hollow" formamidinium lead bromide perovskite nanocrystals; these materials can be successfully printed into fluorescence-lifetime-encoded-quick-read tags that are protected from conventional readers. Furthermore, we also demonstrate that a portable, cost-effective time-of-flight fluorescence-lifetime imaging prototype can also decipher these codes. A single comprehensive approach combining these innovations may be eventually deployed to protect both producers and consumers.

Comparative Genomics of Microbacterium Species to Reveal Diversity, Potential for Secondary Metabolites and Heavy Metal Resistance.

Microbacterium species have been isolated from a wide range of hosts and environments, including heavy metal-contaminated sites. Here, we present a comprehensive analysis on the phylogenetic distribution and the genetic potential of 70 Microbacterium belonging to 20 different species isolated from heavy metal-contaminated and non-contaminated sites with particular attention to secondary metabolites gene clusters. The analyzed Microbacterium species are divided in three main functional clades. They share a small core genome (331 gene families covering basic functions) pointing to high genetic diversity. The most common secondary metabolite gene clusters encode pathways for the production of terpenoids, type III polyketide synthases and non-ribosomal peptide synthetases, potentially responsible of the synthesis of siderophore-like compounds. In vitro tests showed that many Microbacterium strains produce siderophores, ACC deaminase, auxins (IAA) and are able to solubilize phosphate. Microbacterium isolates from heavy metal contaminated sites are on average more resistant to heavy metals and harbor more genes related to metal homeostasis (e.g., metalloregulators). On the other hand, the ability to increase the metal mobility in a contaminated soil through the secretion of specific molecules seems to be widespread among all. Despite the widespread capacity of strains to mobilize several metals, plants inoculated with selected Microbacterium isolates showed only slightly increased iron concentrations, whereas concentrations of zinc, cadmium and lead were decreased.

Tailoring Electronic and Magnetic Properties of Graphene by Phosphorus Doping.

The electronic and magnetic properties of graphene can be modulated by doping it with other elements, especially those with a different number of valence electrons. In this article, we first provide a three-dimensional reconstruction of the atomic structure of a phosphorus substitution in graphene using aberration-corrected scanning transmission electron microscopy. Turning then to theoretical calculations based on the density functional theory (DFT), we show that doping phosphorus in various bonding configurations can induce magnetism in graphene. Our simulations reveal that the electronic and magnetic properties of P-doped (Gr-P) and/or phosphono-functionalized graphene (Gr-PO3H2) can be controlled by both the phosphorus concentration and configurations, ultimately leading to ferromagnetic (FM) and/or antiferromagnetic (AFM) features with the transition temperature up to room temperature. We also calculate core-level binding energies of variously bonded P to facilitate X-ray photoelectron spectroscopy-based identification of its chemical form present in P-doped graphene-based structures. These results may enable the design of graphene-based organic magnets with tailored properties for future magnetic or spintronic applications.

Prediction of Cognitive Decline in Temporal Lobe Epilepsy and Mild Cognitive Impairment by EEG, MRI, and Neuropsychology.

Cognitive decline is a severe concern of patients with mild cognitive impairment. Also, in patients with temporal lobe epilepsy, memory problems are a frequently encountered problem with potential progression. On the background of a unifying hypothesis for cognitive decline, we merged knowledge from dementia and epilepsy research in order to identify biomarkers with a high predictive value for cognitive decline across and beyond these groups that can be fed into intelligent systems. We prospectively assessed patients with temporal lobe epilepsy (N = 9), mild cognitive impairment (N = 19), and subjective cognitive complaints (N = 4) and healthy controls (N = 18). All had structural cerebral MRI, EEG at rest and during declarative verbal memory performance, and a neuropsychological assessment which was repeated after 18 months. Cognitive decline was defined as significant change on neuropsychological subscales. We extracted volumetric and shape features from MRI and brain network measures from EEG and fed these features alongside a baseline testing in neuropsychology into a machine learning framework with feature subset selection and 5-fold cross validation. Out of 50 patients, 27 had a decline over time in executive functions, 23 in visual-verbal memory, 23 in divided attention, and 7 patients had an increase in depression scores. The best sensitivity/specificity for decline was 72%/82% for executive functions based on a feature combination from MRI volumetry and EEG partial coherence during recall of memories; 95%/74% for visual-verbal memory by combination of MRI-wavelet features and neuropsychology; 84%/76% for divided attention by combination of MRI-wavelet features and neuropsychology; and 81%/90% for increase of depression by combination of EEG partial directed coherence factor at rest and neuropsychology. Combining information from EEG, MRI, and neuropsychology in order to predict neuropsychological changes in a heterogeneous population could create a more general model of cognitive performance decline.

An empirical assessment of appearance descriptors applied to MRI for automated diagnosis of TLE and MCI.

OBJECTIVE: Differential diagnosis of mild cognitive impairment MCI and temporal lobe epilepsy TLE is a debated issue, specifically because these conditions may coincide in the elderly population. We evaluate automated differential diagnosis based on characteristics derived from structural brain MRI of different brain regions. METHODS: In 22 healthy controls, 19 patients with MCI, and 17 patients with TLE we used scale invariant feature transform (SIFT), local binary patterns (LBP), and wavelet-based features and investigate their predictive performance for MCI and TLE. RESULTS: The classification based on SIFT features resulted in an accuracy of 81% of MCI vs. TLE and reasonable generalizability. Local binary patterns yielded satisfactory diagnostic performance with up to 94.74% sensitivity and 88.24% specificity in the right Thalamus for the distinction of MCI vs. TLE, but with limited generalizable. Wavelet features yielded similar results as LPB with 94.74% sensitivity and 82.35% specificity but generalize better. SIGNIFICANCE: Features beyond volume analysis are a valid approach when applied to specific regions of the brain. Most significant information could be extracted from the thalamus, frontal gyri, and temporal regions, among others. These results suggest that analysis of changes of the central nervous system should not be limited to the most typical regions of interest such as the hippocampus and parahippocampal areas. Region-independent approaches can add considerable information for diagnosis. We emphasize the need to characterize generalizability in future studies, as our results demonstrate that not doing so can lead to overestimation of classification results. LIMITATIONS: The data used within this study allows for separation of MCI and TLE subjects using a simple age threshold. While we present a strong indication that the presented method is age-invariant and therefore agnostic to this situation, new data would be needed for a rigorous empirical assessment of this findings.

Interchangeability of cardiac output measurements between non-invasive photoplethysmography and bolus thermodilution: A systematic review and individual patient data meta-analysis.

BACKGROUND: Continuous non-invasive cardiac output devices using digital photoplethysmography (PPG) are widely available for bedside use, but their interchangeability with reference methods has not yet been evaluated in a systematic review and patient data meta-analysis. METHODS: A systematic review and meta-analysis of studies comparing non-invasive cardiac output monitoring using PPG with the invasive bolus thermodilution method was performed. With ethical approval, all published studies from the PUBMED, Embase, Scopus, Web of Science, and Google Scholar databases from January 1, 2010 to January 1, 2018 were included. From these analysed studies, individual patient data were interpreted using the interchangeability methods for both absolute values and changes in cardiac output measurements. RESULTS: Ten studies comparing PPG and bolus thermodilution in the operating room and intensive care settings were included. The interchangeability rate (95% CI) was 37% (24-48) (n=1350 pairs of measurements). The interchangeability rate was poorer with the CNAP device (CNSystems, Graz, Austria) [18% (17-20)] than with the Clearsight (Edwards Lifesciences, Irvine, CA) device [33% (31-34), P<0.0001], for patients receiving norepinephrine [19% (17-20) vs. 33% (32-34), P<0.0001], and for patients with low mean arterial pressure (<65mmHg) [26% (23-29) vs. 30% (29-31), P<0.0001]. Among the 1009 comparisons of the changes in cardiac output between both methods, 561 (56%) were interpretable with a trend interchangeability rate at 24% (12-36). CONCLUSIONS: Cardiac output measurements using PPG were not interchangeable with bolus thermodilution in regard to both absolute values and changes in cardiac output measurements, and should be used with caution in clinical practice. TRIAL REGISTRATION: PROSPERO ID CRD42018089513.

Direct imaging of light-element impurities in graphene reveals triple-coordinated oxygen.

Along with hydrogen, carbon, nitrogen and oxygen are the arguably most important elements for organic chemistry. Due to their rich variety of possible bonding configurations, they can form a staggering number of compounds. Here, we present a detailed analysis of nitrogen and oxygen bonding configurations in a defective carbon (graphene) lattice. Using aberration-corrected scanning transmission electron microscopy and single-atom electron energy loss spectroscopy, we directly imaged oxygen atoms in graphene oxide, as well as nitrogen atoms implanted into graphene. The collected data allows us to compare nitrogen and oxygen bonding configurations, showing clear differences between the two elements. As expected, nitrogen forms either two or three bonds with neighboring carbon atoms, with three bonds being the preferred configuration. Oxygen, by contrast, tends to bind with only two carbon atoms. Remarkably, however, triple-coordinated oxygen with three carbon neighbors is also observed, a configuration that is exceedingly rare in organic compounds.