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Pulmonary venous thrombosis (PVT) is a rare but potentially devastating disease state with a largely unknown incidence. The most common etiologies of PVT are secondary to complications of lung surgery, malignancy, catheter ablation for atrial fibrillation, and idiopathic causes. Diagnosis can be challenging because presenting symptoms often are vague and nonspecific, or even asymptomatic, and traditional diagnostic modalities, such as chest radiography and arterial phase computed tomography scans, are poor techniques for diagnosis. The authors present a case of a patient presenting for pulmonary thromboendarterectomy for a presumed diagnosis of chronic thromboembolic pulmonary hypertension who was found incidentally to have a PVT, on intraoperative transesophageal echocardiography. Due to significant thrombus burden, the new finding of PVT, and known association of PVT and malignancy, a biopsy of mediastinal lymph nodes was obtained, which revealed metastatic cervical carcinoma. The pulmonary endarterectomy procedure was aborted. more...

Aims To estimate the prevalence of extended-spectrum-β-lactamase (ESBL)-producing enterobacterales (ESBL-E) carriage in the general population of Lower Saxony, Germany, and to identify risk factors for being colonized. Methods and Results Participants were recruited through local press and information events. Detection of ESBL-E by culture was conducted using ESBL-selective chromagar plates containing third-generation cephalosporins. Identification of pathogens was performed using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)_technology on Vitek mass spectrometry. Antibiotic susceptibility testing was conducted by microdilution (Vitek II) and an ESBL confirmation assay was carried out using a combination disk test. Of 527 randomly collected stool samples from healthy volunteers, 5.5% were tested positive for ESBL-E. Post-stratification for age and gender yielded a similar population estimate (5.9%). People traveling abroad and taking antibiotics had the greatest rectal ESBL-E carriage. Conclusions Potential risk factors (eg, working in healthcare facilities, recent inpatient stay) did not attribute to rectal ESBL-E carriage as other factors (eg, travelling, taking antibiotics). Rectal ESBL-E carriage within the general population seems to be high. Significance and Impact of the Study The known risk factors for carriage with MDRO might not be fully applicable to ESBL-E and require further examination in order to develop effective strategies for the prevention of ESBL-E dissemination within the general population. more...

Haemorrhage and calcification can be qualitatively distinguished on susceptibility-weighted imaging (SWI) using phase information, but it is unclear how to make this distinction in a subset of lesions with ambiguous phase, containing a mixture of positive and negative values. This work investigates the validity of qualitative phase assessment at the cranial or caudal margins in classifying such lesions as haemorrhagic or calcific, when quantitative susceptibility mapping is not available to the neuroradiologist. In a retrospective review of magnetic resonance imaging examinations acquired between July 2015 and November 2019, 87 lesions with ambiguous phase which could be confidently determined to be haemorrhagic or calcific were identified. Two blinded neuroradiologists independently classified these lesions as haemorrhagic or calcific using 3 approaches: qualitative phase assessment at the lesions’ cranial or caudal margins, dominant phase, and in-plane margins. Combined sensitivities and specificities of these analyses were calculated using a generalised linear mixed model with random effects for reader. Assessment at the cranial or caudal margins achieved a sensitivity of 100% for haemorrhage and calcification, which was significantly superior (p more...

Background The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation. Methods We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations. Results Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260). Conclusion We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes. more...

Background Hepatic iron content (HIC) is an important parameter for the management of iron overload. Non-invasive HIC assessment is often performed using biopsy-calibrated two-dimensional breath-hold Cartesian gradient echo (2D BH GRE) R2 * -MRI. However, breath-holding is not possible in most pediatric patients or those with respiratory problems, and three-dimensional free-breathing radial GRE (3D FB rGRE) has emerged as a viable alternative. Purpose To evaluate the performance of a 3D FB rGRE and validate its R2 * and fat fraction (FF) quantification with 3D breath-hold Cartesian GRE (3D BH cGRE) and biopsy-calibrated 2D BH GRE across a wide range of HICs. Study type Retrospective. Subjects Twenty-nine patients with hepatic iron overload (22 females, median age: 15 [5-25] years). Field strength/sequence Three-dimensional radial and 2D and 3D Cartesian multi-echo GRE at 1.5 T. Assessment R2 * and FF maps were computed for 3D GREs using a multi-spectral fat model and 2D GRE R2 * maps were calculated using a mono-exponential model. Mean R2 * and FF values were calculated via whole-liver contouring and T2 * -thresholding by three operators. Statistical tests Inter- and intra-observer reproducibility was assessed using Bland-Altman and intraclass correlation coefficient (ICC). Linear regression and Bland-Altman analysis were performed to compare R2 * and FF values among the three acquisitions. One-way repeated-measures ANOVA and Wilcoxon signed-rank tests, respectively, were used to test for significant differences between R2 * and FF values obtained with different acquisitions. Statistical significance was assumed at P Results The mean biases and ICC for inter- and intra-observer reproducibility were close to 0% and >0.99, respectively for both R2 * and FF. The 3D FB rGRE R2 * and FF values were not significantly different (P > 0.44) and highly correlated (R2 ≥ 0.98) with breath-hold Cartesian GREs, with mean biases ≤ ±2.5% and slopes 0.90-1.12. In non-breath-holding patients, Cartesian GREs showed motion artifacts, whereas 3D FB rGRE exhibited only minimal streaking artifacts. Data conclusion Free-breathing 3D radial GRE is a viable alternative in non-breath-hold patients for accurate HIC estimation. Level of evidence 3 TECHNICAL EFFICACY: Stage 2. more...

Polaritons are hybrid excitations of matter and photons. In recent years, polaritons in van der Waals nanomaterials—known as van der Waals polaritons—have shown great promise to guide the flow of light at the nanoscale over spectral regions ranging from the visible to the terahertz. A vibrant research field based on manipulating strong light–matter interactions in the form of polaritons, supported by these atomically thin van der Waals nanomaterials, is emerging for advanced nanophotonic and opto-electronic applications. Here we provide an overview of the state of the art of exploiting interface optics—such as refractive optics, meta-optics and moire engineering—for the control of van der Waals polaritons. This enhanced control over van der Waals polaritons at the nanoscale has not only unveiled many new phenomena, but has also inspired valuable applications—including new avenues for nano-imaging, sensing, on-chip optical circuitry, and potentially many others in the years to come. This Review discusses the state of the art of interface optics—including refractive optics, meta-optics and moire engineering—for the control of van der Waals polaritons. more...

Phonon polaritons (PhPs) in van der Waals (vdW) crystal slabs enable nanoscale infrared light manipulation. Specifically, periodically structured vdW slabs behave as polaritonic crystals (vdW-PCs), where the polaritons form Bloch modes. Because the polariton wavelengths are smaller than that of light, conventional far-field spectroscopy does not allow for a complete characterization of vdW-PCs or for revealing their band structure. Here, we perform hyperspectral infrared nanoimaging and analysis of PhPs in a vdW-PC slab made of h-BN. We demonstrate that infrared spectra recorded at individual spatial positions within the unit cell of the vdW-PC can be associated with its band structure and local density of photonic states (LDOS). We thus introduce hyperspectral infrared nanoimaging as a tool for the comprehensive analysis of polaritonic crystals, which could find applications in the reconstruction of complex polaritonic dispersion surfaces in momentum-frequency space or for exploring exotic electromagnetic modes in topological photonic structures., A.Y.N., L.M.-M., and S.G.R. acknowledge the Spanish Ministry of Science, Innovation and Universities (grant MAT201788358-C3.) A.Y.N. acknowledges the Basque Department of Education (grant PIBA-2020-1-0014). P.A.-G. acknowledges support from the European Research Council under starting grant no. 715496, 2DNANOPTICA and from the Spanish Ministry of Science and Innovation (State Plan for Scientific and Technical Research and Innovation grant number PID2019-111156GB-I00). R.H., F.C., and L.E.H. acknowledge the Spanish Ministry of Science, Innovation and Universities (national projects MAT2017-88358-C3, RTI2018-094830-B-100, RTI2018-094861-B-100, and the project MDM-2016-0618 of the Maria de Maeztu Units of Excellence Program). A.Y.N. and R.H. acknowledge funding from the Basque Government (grant no. IT1164-19). more...

Terahertz radiation has become an important diagnostic tool in the development of new technologies. However, the diffraction limit prevents terahertz radiation (λ ≈ 0.01–3 mm) from being focused to the nanometre length scale of modern devices. In response to this challenge, terahertz scanning probe microscopy techniques based on coupling terahertz radiation to subwavelength probes such as sharp tips have been developed. These probes enhance and confine the light, improving the spatial resolution of terahertz experiments by up to six orders of magnitude. In this Review, we survey terahertz scanning probe microscopy techniques that achieve spatial resolution on the scale of micrometres to angstroms, with particular emphasis on their overarching approaches and underlying probing mechanisms. Finally, we forecast the next steps in the field. Recent progress in terahertz scanning probe microscopy is reviewed with an emphasis on techniques that access length scales below 100 nm relevant to material science. An outlook on the future of nanoscale terahertz scanning probe microscopy is also provided. more...

Polaritons allow for strong light-matter coupling and for highly sensitive analysis of (bio)chemical substances and processes. Nanoimaging of the polaritons' evanescent fields is critically important for experimental mode identification and field confinement studies. Here we describe two setups for polariton nanoimaging and spectroscopy in liquid. We first demonstrate the mapping of localized plasmon polaritons in metal antennas with a transflection infrared scattering-type scanning near-field optical microscope (s-SNOM), where the tip acts as a near-field scattering probe. We then demonstrate a total internal reflection (TIR)-based setup, where the tip is both launching and probing ultraconfined polaritons in van der Waals materials (here phonon polaritons in hexagonal boron nitride flakes), laying the foundation for s-SNOM-based polariton interferometry in liquid. Our results promise manifold applications, for example, in situ studies of strong coupling between polaritons and molecular vibrations or chemical reactions at the bare or functionalized surfaces of polaritonic materials. more...

Scattering-type scanning near-field optical microscopy (s-SNOM), and its derivate, Fourier transform infrared nanospectroscopy (nano-FTIR) are emerging techniques for infrared (IR) nanoimaging and spectroscopy with applications in diverse fields ranging from nanophotonics, chemical imaging and materials science. However, spectroscopic nanoimaging is still challenged by the limited acquisition rate of current nano-FTIR technology. Here we combine s-SNOM, nano-FTIR and synthetic optical holographic (SOH) to achieve infrared spectroscopic nanoimaging at unprecedented speed (8 spectroscopically resolved images in 20 min), which we demonstrate with a polymer composite sample. Beyond being fast, our method promises to enable nanoimaging in the long IR spectral range, which is covered by IR supercontinuum and synchrotron sources, but not by current quantum cascade laser technology., 17 pages, 4 figures, plus supplementary information more...

When NoSQL database systems are used in an agile software development setting, data model changes occur frequently and thus, data is routinely stored in different versions. The management of versioned data leads to an overhead potentially impeding the software development. Several data migration strategies exist that handle legacy data differently during data accesses, each of which can be characterized by certain advantages and disadvantages. Depending on the requirements for the software application, we evaluate and compare different migration strategies through metrics like migration costs and latency as well as precision and recall. Ideally, exactly that strategy should be selected whose characteristics fulfill service-level agreements and match the migration scenario, which depends on the query workload and the changes in the data model which imply an evolution of the database schema. In this paper, we present a methodology of self-adapting data migration, which automatically adjusts migration strategies and their parameters with respect to the migration scenario and service-level agreements, thereby contributing to the self-management of database systems and supporting agile development. more...

The legacy of the Scientific Committee on Antarctic Research’s (SCAR) PAIS strategic research programme includes not only breakthrough scientific discoveries, but it is also the story of a long-standing deep collaboration amongst different multi-disciplinary researchers from many nations, to share scientific infrastructure and data, facilities, and numerical models, in order to address high priority questions regarding the evolution and behaviour of the Antarctic ice sheets (AIS). The PAIS research philosophy is based on data-data and data-model integration and intercomparison, and the development of ‘ice-to-abyss’ data transects and paleo-environmental, extending from the ice sheet interior to the deep sea. PAIS strives to improve understanding of AIS dynamics and to reduce uncertainty in model simulations of future ice loss and global sea level change, by studying warm periods of the geological past that are relevant to future climate scenarios. The multi-disciplinary approach fostered by PAIS represents its greatest strength. Eight years after the start of this programme, PAIS achievements have been high-profile and impactful, both in terms of field campaigns that collected unique data sets and samples, and in terms of scientific advances concerning past AIS dynamics, that have measurably improved understanding of ice sheet sensitivity in response to global warming. Here we provide an overview and synthesis of the new knowledge generated by the PAIS Programme and its implications for anticipating and managing the impacts of global sea-level rise. more...

Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health. more...

The scattering-type scanning near-field optical microscope (s-SNOM) has emerged as a powerful tool for resolving nanoscale inhomogeneities in laterally heterogeneous samples. However, most analytical models used to predict the scattering near-field signals are assuming homogenous landscapes (bulk materials), resulting in inconsistencies when applied to samples with more complex configurations. In this work, we combine the point-dipole model (PDM) to the finite-element method (FEM) to account for the lateral and vertical heterogeneities while keeping the computation time manageable. Full images, spectra, or hyperspectral line profiles can be simulated by calculating the self-consistent dipole radiation demodulated at higher harmonics of the tip oscillation, mimicking real experimental procedures. Using this formalism, we clarify several important yet puzzling experimental observations in near-field images on samples with rich typography and complex material compositions, heterostructures of two-dimensional material flakes, and plasmonic antennas. The developed method serves as a basis for future investigations of nano-systems with nontrivial topography. more...

Since current battery cell production lines are not flexible regarding format and material, it is necessary to develop new production systems. It is also required to develop this production line as an agile system in order to be able to flexibly counteract unit-specific capacity fluctuations. In addition, only low scrap rates are allowed when integrating new material systems which requires a holistic in-process or in-line control and the associated quality assurance. Agile production systems open up new possibilities for developing the battery cell product. Therefore, this article will present a novel product-production co-design that can be specifically adapted to customer requirements. more...

Background Secondary prevention after embolic stroke of undetermined source (ESUS) has not yet been established. ESUS is associated with high risk of recurrent ischemic stroke and clinically silent ischemic lesions. Secondary prevention with aspirin is the current standard therapy in ESUS patients, despite high prevalence of occult atrial fibrillation (AF). Purpose To determine whether the direct oral factor Xa inhibitor apixaban, started within 28 days after index stroke, is superior to aspirin in preventing new ischemic lesions in subjects with remote cardiac monitoring. Primary endpoint was detection of new ischemic lesions in flair and diffusion-weighted (DWI) MR imaging at 12 months follow-up. Methods The study enrolled ESUS patients with risk profile for cardiac thromboembolism (i.e., left atrium (LA) size >45 mm, spontaneous echo contrast in LA appendage, LA appendage flow velocity ≤0.2 cm/s, atrial high rate episodes, CHA2DS2-Vasc score ≥4, patent foramen ovale). Patients were randomized 1:1 into the aspirin and apixaban arms. Study drug was initiated within 3–28 days after minor/moderate stroke and 14–28 days after major stroke. MRI (Flair/DWI) was conducted within 7 days of AF detection by remote cardiac monitors and at 12 months. ClinicalTrials.gov Identifier: NCT02427126. Funding: The trial is supported by BMS-Pfizer Alliance. Results Enrollment was stopped after interims analysis (including 200 patients) due to futility. Overall, 373 patients were screened with 353 being enrolled (178 and 175 in apixaban and ASA arms, respectively). So far, 130 (73.0%) and 120 (68.6%) subjects from apixaban and ASA arms, respectively, completed the study. 2% death, 1.7% withdrawal, and 1.7% were lost to follow-up. 3.9% did not completed the study for other reasons. Mean age of the ATTICUS population was 68.5 years with 51% males. 80% of the subjects suffered from hypertension. Mean systolic blood pressure at enrollment was 132 mmHg, BMI was 27.7, and CHA2DS-VASc-Score was 4.9. So far, adverse events (AE) occurred in 63% of the subjects, 30% was documented as severe. 6.8% cases of recurrent ischemic stroke and no case of hemorrhagic stroke were reported. Only 1 case of severe bleeding was reported in the aspirin arm. Newly detected AF was reported in 80 patients (23%), 42 occurring in the aspirin arm. As required by protocol, latter were immediately switched from aspirin to apixaban. Due to ongoing data clearing, numbers and % will change until presentation. Conclusions In contrast to the recently published NAVIGATE and RESPECT ESUS trials, patients enrolled in ATTICUS need to exhibit additional AF predicting factors. Furthermore, mandatory cardiac remote monitoring will help to elucidate the impact of AF and the effects of early oral anticoagulation with apixaban compared to antiplatelet therapy with aspirin on the incidence of new ischemic lesions after ESUS. Preliminary data will be presented and discussed in the context of current literature. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The trial is supported by BMS-Pfizer Alliance. more...

Modern scattering-type scanning near-field optical microscopy (s-SNOM) has become an indispensable tool in material research. However, as the s-SNOM technique marches into the far-infrared (IR) and terahertz (THz) regimes, emerging experiments sometimes produce puzzling results. For example, "anomalies" in the near-field optical contrast have been widely reported. In this Letter, we systematically investigate a series of extreme subwavelength metallic nanostructures via s-SNOM near-field imaging in the GHz to THz frequency range. We find that the near-field material contrast is greatly impacted by the lateral size of the nanostructure, while the spatial resolution is practically independent of it. The contrast is also strongly affected by the connectivity of the metallic structures to a larger metallic "ground plane". The observed effect can be largely explained by a quasi-electrostatic analysis. We also compare the THz s-SNOM results to those of the mid-IR regime, where the size-dependence becomes significant only for smaller structures. Our results reveal that the quantitative analysis of the near-field optical material contrasts in the long-wavelength regime requires a careful assessment of the size and configuration of metallic (optically conductive) structures. more...

Ziel der Instandhaltung von Werkzeugmaschinen ist die Verfügbarkeitsabsicherung, um hohe Bauteilqualität und Produktivität zu gewährleisten. Die Kenntnis des Vorschubachsenzustandes, im Besonderen des Kugelgewindetriebs, ist daher von enormer Wichtigkeit. Das „Guard-Plus“-System, eine Entwicklung der August Steinmeyer GmbH und der ifm diagnostics GmbH, ermöglicht dies durch Detektion des Vorspannungsverlustes aufgrund von Verschleiß. Untersuchungen zur Systemfunktion wurden in diesem Beitrag durch das wbk Institut für Produktionstechnik durchgeführt. The aim of machine tool maintenance is to ensure availability in order to guarantee high product quality and productivity. Knowledge of the wear condition of feed axes involved, especially the ball screw, is therefore of enormous importance. The Guard Plus system, a joint development of August Steinmeyer GmbH and ifm diagnostics GmbH, enables this by detecting the preload loss due to wear. Investigation of the system’s function are presented through wbk Institute of Production Science in the following article. more...

Introduction and Objective: Typical symptoms for primary hyperparathyroidism (pHPT) include osteoporosis, bone or joint pain, and nephrolithiasis, as well as fatigue, depression, gastritis, and cardiovascular disease. The female:male ratio was 3:1. The aim of this retrospective study was to evaluate the possible influence of gender-specific aspects of these symptoms. Methods: From February 2018 to November 2019, parathyroid surgery was performed in 125 patients with pHPT (age: 23–83 years); 95 (76%) were female, and 30 (24%) were male. Preoperatively, a standardized medical history including 7 typical symptoms of pHPT was used for routine clinical documentation according to the StuDoQ Thyroid and Parathyroid Registry. Results: For both groups (mean age: 60.4 years for females and 60.2 years for males), no sex differences were found in serum calcium or parathyroid hormone levels. For females, there was a tendency towards smaller hyperfunctioning parathyroid glands (16.8 vs. 20.5 mm) with less weight (1.14 vs. 1.52 g) and multiglandular disease. Nephrolithiasis was significantly more frequent in men than in women (36.7 vs. 16.8%, respectively; p = 0.036), but the difference in hypertension was not significant (60% in men vs. 47.4% in women, p = 0.230). Women reported significantly more often bone and joint pain (44.2% in women vs. 20% in men, p = 0.053) and depressive episodes (32.6% in women vs. 10% in men, p = 0.016). Conclusion: 91.2% of patients transferred for parathyroidectomy described typical symptoms of pHPT. However, an unexpected high gender difference was found following the analysis of symptoms documented in the StuDoQ Registry. more...

We might flatter ourselves that the idea of a spin doctor is rather a modern one, but I wonder. Obviously enough, powerful rulers have always had their coterie of close advisers. But in the medieval Muslim world there is one outstanding example of something rather more than this: the team of three counsellors that Saladin assembled who watched over his interests and, crucially, his reputation, with unflagging devotion for decades. Two of them were, by any standard, intellectual stars who could have turned their multifarious talents in many directions but who chose rather to dedicate them to a man whom they not only admired but also loved. One of them, the poet ‘Imad al-Din al-Isfahani, was a Persian with a truly awesome command of Arabic, a gift which he delighted to exhibit in and out of season. His pyrotechnic performances, solid with metaphor, saturated with puns, wordplay, alliteration, assonance and verbal acrobatics, are such a nightmare to understand that generations of Western Orientalists – and indeed Arab scholars too, for that matter – have recoiled from the task of editing certain of his works. Sometimes in his writings manner eclipses matter, but he is also capable of reaching heights of solemn eloquence, as in his paean of triumph at the recapture of Jerusalem, or his threnody on the death of Saladin. The other, the Qadi al-Fadil – his title means ‘The Excellent Judge’ – though only a somewhat pedestrian poet, was an acknowledged master of the epistolary prose that was de rigueur in Islamic chanceries, and for centuries his letters were regarded as models of their genre. His appearance, hunchbacked and skeletal, made him the butt of the court's satirical poets, but his political skills were beyond reproach, and indeed in his master's absence he governed Egypt for a time. It has been said that biography adds an extra terror to death, but in that respect Saladin need not have worried. For Ibn Shaddad, the third member of this distinguished triumvirate, who joined the team after the fall of Jerusalem but thereafter never left Saladin's side and therefore saw him in good times and bad, was a plain man with a plain style. But he rose to the occasion and crafted a biography of his hero Saladin that lets the facts speak for themselves. He has no time for stale panegyric; instead, his admiration for Saladin shines through his account at every turn, and it is he who laid the foundations for his master's posthumous celebrity. The lecture will explore the impact of these three men on the Saladin legend, which transformed a minor Kurdish warlord into an emblem of chivalry, piety and military glory which captured the hearts and the imaginations of Muslims for centuries to come – and still does. more...

Background Hyperactivity of the IL-23/IL-17 axis is central to plaque psoriasis pathogenesis. Secukinumab, a fully human mAb that selectively inhibits IL-17A, is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab improves the complete spectrum of psoriasis manifestations, with durable clinical responses beyond 5 years of treatment. In the feed-forward model of plaque chronicity, IL-17A has been hypothesized as the key driver of pathogenic gene expression by lesional keratinocytes, but in vivo evidence in human subjects is lacking. Methods We performed a randomized, double-blind, placebo-controlled study (NCT01537432) of patients receiving secukinumab at the clinically approved dose up to 12 weeks. We then correlated plaque and nonlesional skin transcriptomic profiles with histopathologic and clinical measures of efficacy. Results After 12 weeks of treatment, secukinumab reversed plaque histopathology in the majority of patients and modulated thousands of transcripts. Suppression of the IL-23/IL-17 axis by secukinumab was evident at week 1 and continued through week 12, including reductions in levels of the upstream cytokine IL-23, the drug target IL-17A, and downstream targets, including β-defensin 2. Suppression of the IL-23/IL-17 axis by secukinumab at week 4 was associated with clinical and histologic responses at week 12. Secukinumab did not affect ex vivo T-cell activation, which is consistent with its favorable long-term safety profile. Conclusion Our data suggest that IL-17A is the critical node within the multidimensional pathogenic immune circuits that maintain psoriasis plaques and that early reduction of IL-17A–dependent feed-forward transcripts synthesized by hyperplastic keratinocytes favors plaque resolution. more...

Background. Primary hyperparathyroidism (pHPT) is a common endocrine disorder of the parathyroid glands. In most cases pHPT is caused by single gland disease, but about 10% of patients suffer from sporadic multiglandular disease (MGD). Patients with MGD, especially with ectopic parathyroid adenomas, have an increased risk for persistence/recurrence after surgery. Normally, sporadic MGD cannot be diagnosed preoperatively by parathyroid scintigraphy. We analyzed the potential of positron emission tomography/computed tomography (Met-PET/CT) to predict MGD. Methods and Case Presentation. We reviewed the literature, if preoperative Met-PET/CT could predict MGD in patients with pHPT. Further, we present a 71-year-old female with ectopic MGD. Preoperative localization via Met-PET/CT showed MGD with two areas suspected to be enlarged parathyroid glands (left lateral to the thyroid lobe and posterior mediastinum). Both diagnostic findings were extirpated and parathormone dropped into normal levels. Results. We identified four additional manuscripts, referring to MGD and Met-PET/CT with divergent results. Preoperative localization diagnostics using Met-PET/CT may not necessarily identify MGD. In most cases, Met-PET/CT localized only one adenoma and localizes larger adenomas more reliably than smaller adenomas. Conclusion. Identifying patients at risk of MGD preoperatively remains challenging. We found MET-PET/CT seems to predict MGD in patients with large size and high weight PTH adenomas. For ectopic parathyroid adenomas, accurate preoperative localization is the key to successful surgical removal. Met-PET/CT appears to have great potential in soft-tissue analysis of complex anatomical regions and can predict ectopic parathyroid adenomas. more...

BACKGROUND: Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri‑, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. METHODS: We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980. FINDINGS: Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2-2.5) and tobacco smoke (OR 1.5; 95% CI 1.2-1.9), and early life otitis media (OR 2.1; 95% CI 1.2-3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous. INTERPRETATION: Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies. FUNDING: This study did not receive any funding. ispartof: ECLINICALMEDICINE vol:36 ispartof: location:England status: published more...

Nanoscale magnetic systems play a decisive role in areas ranging from biology to spintronics. Although, in principle, THz electron paramagnetic resonance (EPR) provides high-resolution access to their properties, lack of sensitivity has precluded realizing this potential. To resolve this issue, the principle of plasmonic enhancement of electromagnetic fields that is used in electric dipole spectroscopies with great success is exploited, and a new type of resonators for the enhancement of THz magnetic fields in a microscopic volume is proposed. A resonator composed of an array of diabolo antennas with a back-reflecting mirror is designed and fabricated. Simulations and THz EPR measurements demonstrate a 30-fold signal increase for thin film samples. This enhancement factor increases to a theoretical value of 7500 for samples confined to the active region of the antennas. These findings open the door to the elucidation of fundamental processes in nanoscale samples, including junctions in spintronic devices or biological membranes. more...

The collection of the Imperial War Museum contains an object with a more than usually chequered history. When in 1899 the German Kaiser Wilhelm II undertook something of a state visit to the domains of his close ally, the Ottoman ruler ‘Abd al-Hamid, he ordered, as a gesture of respect, a gold wreath to be made in honour of Saladin, whose cult in Europe had reached new heights in that century. It features a small but elaborate monogram in contemporary German style and long inscriptions in cursive Arabic, which remain unpublished. The Kaiser presented it ceremoniously at the tomb of the Ayyubid sultan Saladin in Damascus. But it was not destined to remain there for long, since less than two decades later Lawrence of Arabia made off with it, and the wreath ended its travels in the Imperial War Museum. This chapter analyses the background to this extraordinary artefact and deciphers its Arabic inscriptions accurately for the first time. more...

Background R2*-MRI is clinically used to noninvasively assess hepatic iron content (HIC) to guide potential iron chelation therapy. However, coexisting pathologies, such as fibrosis and steatosis, affect R2* measurements and may thus confound HIC estimations. Purpose To evaluate whether a multispectral auto regressive moving average (ARMA) model can be used in conjunction with quantitative susceptibility mapping (QSM) to measure magnetic susceptibility as a confounder-free predictor of HIC. Study type Phantom study and in vivo cohort. Subjects Nine iron phantoms covering clinically relevant R2* range (20-1200/second) and 48 patients (22 male, 26 female, median age 18 years). Field strength/sequence Three-dimensional (3D) and two-dimensional (2D) multi-echo gradient echo (GRE) at 1.5 T. Assessment ARMA-QSM modeling was performed on the complex 3D GRE signal to estimate R2*, fat fraction (FF), and susceptibility measurements. R2*-based dry clinical HIC values were calculated from the 2D GRE acquisition using a published R2*-HIC calibration curve as reference standard. Statistical tests Linear regression analysis was performed to compare ARMA R2* and susceptibility-based estimates to iron concentrations and dry clinical HIC values in phantoms and patients, respectively. Results In phantoms, the ARMA R2* and susceptibility values strongly correlated with iron concentrations (R2 ≥ 0.9). In patients, the ARMA R2* values highly correlated (R2 = 0.97) with clinical HIC values with slope = 0.026, and the susceptibility values showed good correlation (R2 = 0.82) with clinical dry HIC values with slope = 3.3 and produced a dry-to-wet HIC ratio of 4.8. Data conclusion This study shows the feasibility that ARMA-QSM can simultaneously estimate susceptibility-based wet HIC, R2*-based dry HIC and FFs from a single multi-echo GRE acquisition. Our results demonstrate that both, R2* and susceptibility-based wet HIC values estimated with ARMA-QSM showed good association with clinical dry HIC values with slopes similar to published R2*-biopsy HIC calibration and dry-to-wet tissue weight ratio, respectively. Hence, our study shows that ARMA-QSM can provide potentially confounder-free assessment of hepatic iron overload. Level of evidence 3 TECHNICAL EFFICACY: Stage 2. more...

This paper examines the impacts of retail borrowers’ emotions and personality traits on their abilities to engage in appropriate responses when things unexpectedly go wrong and they get into debt repayment difficulties. We establish several scenarios where borrowers are hit with unforeseen circumstances that affect their abilities to make their loan payments and we classify and evaluate the riskiness of the strategies they state that they would adopt in those situations. Via an extensive on-line survey conducted in the UK, we show that borrowers who were most comfortable about taking on debts in the first place, those who show neurotic tendencies, and those who believe that they have control over events rather than being controlled by them, are more likely to undertake high risk strategies when faced with unforeseen issues that affect their ability to meet their debt interest and repayment costs. We also find that respondents who identify as feeling excited, alert or guilty, as well as younger borrowers and those who are single or renters, are more likely to opt for risky approaches. Our findings have potentially important implications for lenders, regulators and debt counselling services regarding the types of people who are most likely to get into debt troubles. more...

BackgroundThere is an urgent need for tools allowing the early prognosis and subsequent monitoring of individuals with heterogeneous COVID-19 disease trajectories. Pre-existing cardiovascular (CV) disease is a leading risk factor for COVID-19 susceptibility and poor outcomes, and cardiac involvement is prevalent in COVID-19 patients both during the acute phase as well as in convalescence. The utility of traditional CV risk biomarkers in mild COVID-19 disease or across disease course is poorly understood. We sought to determine if a previously validated 27-protein predictor of CV outcomes served a purpose in COVID-19.MethodsThe 27-protein test of residual CV (RCV) risk was applied without modification to n=860 plasma samples from hospitalized and non-hospitalized SARS-CoV-2 infected individuals at disease presentation from three independent cohorts to predict COVID-19 severity and mortality. The same test was applied to an additional n=991 longitudinal samples to assess sensitivity to change in CV risk throughout the course of infection into convalescence.ResultsIn each independent cohort, RCV predictions were significantly related to maximal subsequent COVID-19 severity and to mortality. At the baseline blood draw, the mean protein-predicted likelihood of an event in subjects who died during the study period ranged from 88-99% while it ranged from 8-36% in subjects who were not admitted to hospital. Additionally, the test outperformed existing risk predictors based on commonly used laboratory chemistry values or presence of comorbidities. Application of the RCV test to sequential samples showed dramatic increases in risk during the first few days of infection followed by risk reduction in the survivors; a period of catastrophically high cardiovascular risk (above 50%) typically lasted 8-12 days and had not resolved to normal levels in most people within that timescale.ConclusionsThe finding that a 27-protein candidate CV surrogate endpoint developed in multi-morbid patients prior to the pandemic is both prognostic and acutely sensitive to the adverse effects of COVID-19 suggests that this disease activates the same biologic risk-related mechanisms. The test may be useful for monitoring recovery and drug response. more...

The school closures during the COVID-19 outbreak triggered ashift towards digital learning. Whilst this is amajor challenge for mainstream education, the implementation of digital learning poses an... more...

Little is known to date regarding how the framing of investment communication impacts retail investor propensity to engage with financial products. To explore this lacuna, we apply insights from regulatory focus theory and construal level theory, and we vary investment communications in terms of the motivation (protect versus achieve) and the time-horizon (distant versus near) presented in a 2x2 quasi-experimental design. We also include an analysis of investor characteristics and find that communication of ‘short-term achieve’ investments attract particularly risk-tolerant and sensation-seeking individuals, posing questions of responsibility towards potentially vulnerable groups. We also find that negative attitudes towards finance may be troublesome as they can stop individuals from engaging with ‘long-term’ investment products. Positive attitudes towards finance, on the other hand, lead investors to engage with ‘protect’ products of both ‘short-‘ and ‘long-term’ horizon, highlighting benefits for individuals and society from interventions aimed at financial education and exposure. The study concludes by discussing insights for the literature and practitioners from the application of new theory and new data to the management of investment communications. more...

During the development of NoSQL-backed software, the database schema evolves naturally alongside the application code. Especially in agile development, new application releases are deployed frequently. Eventually, decisions have to be made regarding the migration of versioned legacy data which is persisted in the cloud-hosted production database. We address this schema evolution problem and present results by means of which software project stakeholders can manage the operative costs for schema evolution and adapt their software release strategy accordingly in order to comply with service-level agreements regarding the competing metrics of migration costs and latency. We clarify conclusively how schema evolution in NoSQL databases impacts these metrics while taking all relevant characteristics of migration scenarios into account. As calculating all combinatorics in the search space of migration scenarios by far exceeds computational means, we use a probabilistic Monte Carlo method of repeated sampling, serving as a well-established method to bring the complexity of schema evolution under control. more...

Refraction between isotropic media is characterized by light bending towards the normal to the boundary when passing from a low- to a high-refractive-index medium. However, refraction between anisotropic media is a more exotic phenomenon which remains barely investigated, particularly at the nanoscale. Here, we visualize and comprehensively study the general case of refraction of electromagnetic waves between two strongly anisotropic (hyperbolic) media, and we do it with the use of nanoscale-confined polaritons in a natural medium: α-MoO3. The refracted polaritons exhibit non-intuitive directions of propagation as they traverse planar nanoprisms, enabling to unveil an exotic optical effect: bending-free refraction. Furthermore, we develop an in-plane refractive hyperlens, yielding foci as small as λp/6, being λp the polariton wavelength (λ0/50 compared to the wavelength of free-space light). Our results set the grounds for planar nano-optics in strongly anisotropic media, with potential for effective control of the flow of energy at the nanoscale., G.Á.-P. and J.T.-G. acknowledge support through the Severo Ochoa Program from the Government of the Principality of Asturias (nos. PA-20-PF-BP19-053 and PA-18-PF-BP17-126, respectively). S.X. acknowledges the support from Independent Research Fund Denmark (Project No. 9041-00333B). B.C. acknowledges the support from VILLUM FONDEN (No. 00027987). The Center for Nanostructured Graphene is sponsored by the Danish National Research Foundation (Project No. DNRF103.) K.V.V. and V.S.V. gratefully acknowledge the financial support from the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2021-606). J.M.-S. acknowledges financial support through the Ramón y Cajal Program from the Government of Spain (RYC2018-026196-I). A.Y.N. and J.I.M. acknowledge the Spanish Ministry of Science, Innovation and Universities (national projects MAT201788358-C3-3-R and PID2019-104604RB/AEI/10.13039/501100011033). R.H. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (national project RTI2018-094830-B-100 and the project MDM-2016-0618 of the Marie de Maeztu Units of Excellence Program) and the Basque Government (grant No. IT1164-19). A.Y.N. also acknowledges the Basque Department of Education (grant no. PIBA-2020-1-0014). P.A.-G. acknowledges support from the European Research Council under starting grant no. 715496, 2DNANOPTICA and the Spanish Ministry of Science and Innovation (State Plan for Scientific and Technical Research and Innovation grant number PID2019-111156GB-I00). more...

The Zwicky Transient Facility (ZTF) has been observing the entire northern sky since the start of 2018 down to a magnitude of 20.5 (5σ for 30 s exposure) in the g, r, and i filters. Over the course of two years, ZTF has obtained light curves of more than a billion sources, each with 50–1000 epochs per light curve in g and r, and fewer in i. To be able to use the information contained in the light curves of variable sources for new scientific discoveries, an efficient and flexible framework is needed to classify them. In this paper, we introduce the methods and infrastructure that will be used to classify all ZTF light curves. Our approach aims to be flexible and modular and allows the use of a dynamical classification scheme and labels, continuously evolving training sets, and the use of different machine-learning classifier types and architectures. With this setup, we are able to continuously update and improve the classification of ZTF light curves as new data become available, training samples are updated, and new classes need to be incorporated. more...

Eighty-five percent of multiple sclerosis cases begin with a discrete attack termed clinically isolated syndrome, but 37% of clinically isolated syndrome patients do not experience a relapse within 20 years of onset. Thus, the identification of biomarkers able to differentiate between individuals who are most likely to have a second clinical attack from those who remain in the clinically isolated syndrome stage is essential to apply a personalized medicine approach. We sought to identify biomarkers from biochemical, metabolic and proteomic screens that predict clinically defined conversion from clinically isolated syndrome to multiple sclerosis and generate a multi-omics-based algorithm with higher prognostic accuracy than any currently available test. An integrative multi-variate approach was applied to the analysis of cerebrospinal fluid samples taken from 54 individuals at the point of clinically isolated syndrome with 2–10 years of subsequent follow-up enabling stratification into clinical converters and non-converters. Leukocyte counts were significantly elevated at onset in the clinical converters and predict the occurrence of a second attack with 70% accuracy. Myo-inositol levels were significantly increased in clinical converters while glucose levels were decreased, predicting transition to multiple sclerosis with accuracies of 72% and 63%, respectively. Proteomics analysis identified 89 novel gene products related to conversion. The identified biochemical and protein biomarkers were combined to produce an algorithm with predictive accuracy of 83% for the transition to clinically defined multiple sclerosis, outperforming any individual biomarker in isolation including oligoclonal bands. The identified protein biomarkers are consistent with an exaggerated immune response, perturbed energy metabolism and multiple sclerosis pathology in the clinical converter group. The new biomarkers presented provide novel insight into the molecular pathways promoting disease while the multi-omics algorithm provides a means to more accurately predict whether an individual is likely to convert to clinically defined multiple sclerosis., Graphical Abstract Graphical Abstract more...

Little is known in the current literature about the factors affecting retail investor (RI) propensity to engage with financial products other than their attitude towards financial risk (ATFR). This study explores the role of a number of variables, thematically grouped into domain-specific (product information and attitudes towards finance) and general impact factors (life variables). Data from 970 UK-based RIs, collected in 2017 across a variant of products, suggest that when analysed thematically, variables related to product information emerge as the most important group of influence factors. While the relevance of ATFR is also vindicated in the findings of this study, the results bring a dose of life-context to situations of financial decision-making by illustrating that information about the product as well as life variables matter significantly, in particular negative emotions and sensation seeking – thereby highlighting a duty of care towards potentially vulnerable people. The study discusses implications arising from the findings in relation to research, practice and policy. more...

This paper presents a method for machine component supervision with little to none prior knowledge of the machine, operating conditions and wear behavior. A hybrid approach based on unsupervised learning methods, consisting of an autoencoder network and clustering, to identify machine states and possible failure preceding anomalies is proposed. In order to cope with information sparsity, the model parameters of the unsupervised methods are derived automatically based on data distribution and a physical motivation. The approach was validated on a dataset of artificially introduced bearing faults. The gained clustering results show a general usability of the approach for condition monitoring with vibration data. more...

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p more...

When NoSQL database systems are used in an agile software development setting, data model changes occur frequently and thus, data is routinely stored in different versions. This leads to an overhead affecting the software development and in particular, the management of data accesses. In this context, different data migration strategies exist, which are characterized by certain advantages and disadvantages. Using exactly that strategy whose characteristics match the according migration scenario, depends on the query workload, the changes in the data model caused by schema evolution, and the requirements for the application in terms of migration costs and latency during data accesses. In this paper we present a methodology of selfadapting data migration, which automatically adjusts migration strategies and its parameters accordingly, thereby supporting the agile software development. more...

The diagnosis of an inguinal hernia is usually made clinically. Precise imaging appears to be necessary when the clinical examination is inconclusive. The aim of this study was to determine the diagnostic value of ultrasonography for inguinal hernias and whether it influences the decision for or against surgery. This study was a single-center retrospective study carried out from January 2012 to December 2016. All 326 patients had undergone ultrasound scanning of the groin as part of the diagnostic workup. Besides surgical findings being the gold standard, follow-up data and alternative ultrasound diagnoses were considered as references, allowing us to assess the accuracy of negative ultrasound findings as well. The findings on ultrasonography were positive in 248 patients and negative in 78 patients. In addition to 201 operated patients, we were able to validate a further 40 patients by means of a questionnaire and the alternative ultrasound diagnoses. The correlation with all three references resulted in a sensitivity of 97 %, a specificity of 77 %, a positive predictive value of 95 %, and a negative predictive value of 87 %. Ultrasonography is an accurate method for evaluating inguinal hernias. High sensitivity makes it particularly suitable for ruling out an inguinal hernia when the findings are negative. An ultrasound scan carried out in addition to clinical examination can therefore help to determine the right indication for surgical intervention.ZIEL: Leistenhernien werden primär klinisch diagnostiziert. Eine genaue Bildgebung erscheint notwendig, wenn die klinische Untersuchung kein eindeutiges Ergebnis liefert. Ziel dieser Studie war es, die Wertigkeit der Sonografie in der Diagnostik von Leistenhernien zu bestimmen und deren Einfluss in der Entscheidungsfindung für oder gegen eine Operation herauszuarbeiten. Es handelte sich bei dieser Studie um eine retrospektive Studie, die als Single-Center-Studie von Januar 2012 bis Dezember 2016 durchgeführt wurde. Untersucht wurden 326 Patienten, die zur differentialdiagnostischen Abklärung eine Ultraschalluntersuchung der Leiste erhalten hatten. Neben Operationsbefunden als Goldstandard wurden Angaben aus einem Follow-up und alternative sonografische Diagnosen als Referenz betrachtet, um den Stellenwert der Sonografie bei negativen Ultraschallbefunden möglichst genau einschätzen zu können. Die Sonografie war bei 248 Patienten positiv und bei 78 Patienten negativ. 201 Patienten wurden operiert und weitere 40 Patienten konnten durch einen Fragebogen und die alternativen sonografischen Diagnosen validiert werden. Die Korrelation mit diesen Referenzen ergab eine Sensitivität von 97 %, eine Spezifität von 77 %, einen positiv prädiktiven Wert von 95 % und einen negativ prädiktiven Wert von 87 %. Die Sonografie stellt eine sehr genaue Methode für die Evaluierung von Leistenhernien dar. Mit einer hohen Sensitivität eignet sie sich bei einem negativen Ultraschallbefund insbesondere gut zum Ausschluss einer Leistenhernie. Eine zusätzlich zur klinischen Untersuchung durchgeführte Sonografie kann daher die korrekte Indikation und Entscheidung für eine chirurgische Intervention vereinfachen. more...

In NF 1 patients, significant numbers of so-called unidentified bright objects (UBOs) can be found. The aim of the study was to investigate whether the detectability of UBOs increases at 3T by comparing Proton density-weighted images (PDw) with fluid-attenuated inversion recovery (FLAIR) sequences.A total of 14 NF1 patients (7 male, 7 female, between 8 and 26 years old, mean age 15.4 years) were examined by a 3T magnetic resonance scanner. The presence of UBOs was evaluated on PD-w and FLAIR images by 4 evaluators. Detectability was rated by a three-point scoring system: lesions which were "well defined/detectable", "suspicious" or "detected after a second look". The Wilcoxon signed-rank test was used for comparisons between the raters. The level of significance was P 0.05.Significantly more lesions were marked as "well defined/detectable" in the PD-w Sequence compared to FLAIR at 3T (P 0.001 for all four evaluators together, as well as for each evaluator separately). In particular, PD-w proved to be superior for detecting UBOs located in the medulla oblongata, dentate nucleus and hippocampal region, regardless of the level of the raters' experience.This is the first study which compares FLAIR and PD-w at 3T for the diagnosis of UBOs in NF1. At this field strength significantly more UBOs were detected in the PD-w compared to FLAIR sequences, especially for the infratentorial regions. As UBOs occur at very early stages of the disease in patients with suspected NF1, PD-w might aid in the early diagnosis when using 3T scanners. more...

Alveolar echinococcosis (AE) is a life-threatening helminthic disease. In humans, AE mostly affects the liver; the regional hepatic lymph nodes may be involved, indicating dissemination of AE from the liver. To achieve complete removal of the disease, enlarged hepatic lymph nodes may be resected during surgical treatment. We evaluated the frequency of affected lymph nodes by conventional microscopic and immunohistochemical analyses including detection of small particles of Echinococcus multilocularis (spem). Furthermore, we analyzed the association of resection of enlarged and affected lymph nodes with long-term outcome after surgical therapy of patients who underwent surgery with curative intent. We identified 43 patients who underwent hepatic surgery with curative intent with lymph node resection for AE. We analyzed the cohort for the manifestation of the parasite in the resected lymph nodes by conventional histology and by immunohistochemistry and compared these data with the further course of AE. Microscopically infected lymph nodes (laminar layer visible) were found in 7 out of these 43 patients (16%). In more than three quarters (25/32) of all specimens investigated, lymph nodes showed spems when stained with antibody against Em2G11, a monoclonal antibody specific for the Em2 antigen of the Echinococcus multilocularis metacestode. Most frequently, lymph nodes were resected due to enlargement. The median size of microscopically affected lymph nodes was 2 cm (range, 1.2 to 2.5 cm), the median size of immunohistochemically and non-affected lymph nodes was 1.3 cm each (range, “small” to 2.3 or 2.5 cm, respectively). Median follow-up was 8 years for all patients, 5 years for patients with lymph node resection, and 4 years for patients with infested lymph nodes. Overall, recurrent disease was seen in ten patients (10/109; 9%) after a median period of 1.5 years (range, 4 months to 4 years). None of the seven patients with conventionally microscopically affected lymph nodes suffered from recurrent disease. One patient with negative resected nodes and one patient with spems showed recurrent disease after 4 and 35 months, respectively. Lymph node involvement in AE is frequent, particularly when evaluated by immunohistochemical examination of lymph nodes with the monoclonal antibody Em2G11. Affected lymph nodes tend to be larger in size. Lymph node involvement is not associated with recurrent disease and therefore warrants further analysis of the biological significance of lymph node involvement. more...

Tip-enhanced Raman spectroscopy (TERS) and scattering-type scanning near-field optical microscopy (s-SNOM) enable optical imaging with a spatial resolution far below the diffraction limit of light. Although s-SNOM records the elastically scattered light (yielding information about the local refractive index and absorption), in TERS, the Raman scattered light is detected, which provides, for example, chemical information. Here, we introduce a combined TERS and s-SNOM setup for correlative studies of tip-enhanced elastically scattered and Raman scattered light. To that end, we equipped a conventional s-SNOM with a grating spectrometer. We validate our setup by characterizing a sample consisting of a self-assembled para-nitrothiophenol monolayer on an Au surface. Comparing s-SNOM and TERS signals, we demonstrate a qualitative correlation between the tip-enhanced elastic and tip-enhanced Raman scattered light. Thus, recording the tip-enhanced elastically scattered light enables a fast and reliable TERS alignm... more...