•Energy dispersive X-Ray spectroscopy was successfully added to a low energy electron microscope/photo electron emission microscope (LEEM/PEEM).•Unwanted scatered electrons were removed from the ...signal by a compact electrostatic deflector.•High quality EDS spectra were obtained on a variety of samples, and over a broad range of incident electron energies.•EDS add elemental detection capability to LEEM, which has been missing in the past.•The solution presented here can be easily added to new and existing LEEM/PEEM systems worldwide.
Energy-Dispersive X-Ray Spectroscopy (EDS) is a technique frequently used in Scanning and Transmission Electron Microscopes to study the elemental composition of a sample. Briefly, high energy electrons of the incident electron beam may ionize an electron from a core shell. The decay of this excited state may result in the emission of a characteristic X-ray photon or Auger-Meitner electron. A solid-state EDS detector captures the X-ray photon and determines its energy. The energy spectrum thus contains information on the elemental make-up of the sample. Low Energy Electron Microscopy (LEEM) typically utilizes incident electrons with energies in the range 0–100 eV, insufficient for the generation of elemental X-rays. In general, LEEM does therefore not allow for elemental characterization of the sample under study. Here we show how relatively simple modifications and additions to the LEEM instrument make in-situ EDS spectroscopy possible, and how high-quality EDS spectra can be obtained, thus enabling elemental analysis in LEEM instruments for the first time.
The control of compliant robots is, due to their often nonlinear and complex dynamics, inherently difficult. The vision of morphological computation proposes to view these aspects not only as ...problems, but rather also as parts of the solution. Non-rigid body parts are not seen anymore as imperfect realizations of rigid body parts, but rather as potential computational resources. The applicability of this vision has already been demonstrated for a variety of complex robot control problems. Nevertheless, a theoretical basis for understanding the capabilities and limitations of morphological computation has been missing so far. We present a model for morphological computation with compliant bodies, where a precise mathematical characterization of the potential computational contribution of a complex physical body is feasible. The theory suggests that complexity and nonlinearity, typically unwanted properties of robots, are desired features in order to provide computational power. We demonstrate that simple generic models of physical bodies, based on mass-spring systems, can be used to implement complex nonlinear operators. By adding a simple readout (which is static and linear) to the morphology such devices are able to emulate complex mappings of input to output streams in continuous time. Hence, by outsourcing parts of the computation to the physical body, the difficult problem of learning to control a complex body, could be reduced to a simple and perspicuous learning task, which can not get stuck in local minima of an error function.
This brief note addresses the historical background of the invention of the enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA). These assays were developed independently and ...simultaneously by the research group of Peter Perlmann and Eva Engvall at Stockholm University in Sweden and by the research group of Anton Schuurs and Bauke van Weemen in The Netherlands. Today, fully automated instruments in medical laboratories around the world use the immunoassay principle with an enzyme as the reporter label for routine measurements of innumerable analytes in patient samples. The impact of EIA/ELISA is reflected in the overwhelmingly large number of times it has appeared as a keyword in the literature since the 1970s. Clinicians and their patients, medical laboratories, in vitro diagnostics manufacturers, and worldwide healthcare systems owe much to these four inventors.
In localized nonsmall cell lung cancer (NSCLC) systemic recurrences after surgery are common. Therefore, adjuvant or neoadjuvant chemotherapy is used. With the advent of immune checkpoint inhibitors ...(ICIs) in metastatic disease the question is whether ICIs can further improve the outcome.
In several phase I/II trials, major pathological response (MPR) rates with several ICIs between 7% and 50% were seen. No major additional side effects occurred. In combination with chemotherapy CheckMate-816 randomized additional neoadjuvant nivolumab and achieved a high pathological complete response (pCR) rate and a better event-free survival (EFS) - without negatively influencing surgery. More randomized trials are performed with neoadjuvant immunochemotherapy and adjuvant treatment after surgery. In Keynote-671, pembrolizumab is used pre and postoperatively with a significantly higher EFS rate at 2 years (62.4% vs. 40.6%). Similar preliminary results are reported in the AEGEAN (durvalumab) and Neotorch (toripalimab) trials. Higher tumour stage and MPR, partly programmed cell death 1 ligand 1 (PD-L1) expression, tumour mutational burden (TMB) and circulating tumour DNA (ctDNA) are correlated with efficacy.
Neoadjuvant immunochemotherapy improves MPR and EFS rates, especially in more advanced tumours and tumours expressing PD-L1 - without relevantly increasing toxicities. But further and longer evaluation is needed.
In large cohort studies comorbidities are usually self-reported by the patients. This way to collect health information only represents conditions known, memorized and openly reported by the ...patients. Several studies addressed the relationship between self-reported comorbidities and medical records or pharmacy data, but none of them provided a structured, documented method of evaluation. We thus developed a detailed procedure to compare self-reported comorbidities with information on comorbidities derived from medication inspection. This was applied to the data of the German COPD cohort COSYCONET.
Approach I was based solely on ICD10-Codes for the diseases and the indications of medications. To overcome the limitations due to potential non-specificity of medications, Approach II was developed using more detailed information, such as ATC-Codes specific for one disease. The relationship between reported comorbidities and medication was expressed by a four-level concordance score.
Approaches I and II demonstrated that the patterns of concordance scores markedly differed between comorbidities in the COSYCONET data. On average, Approach I resulted in more than 50% concordance of all reported diseases to at least one medication. The more specific Approach II showed larger differences in the matching with medications, due to large differences in the disease-specificity of drugs. The highest concordance was achieved for diabetes and three combined cardiovascular disorders, while it was substantial for dyslipidemia and hyperuricemia, and low for asthma.
Both approaches represent feasible strategies to confirm self-reported diagnoses via medication. Approach I covers a broad spectrum of diseases and medications but is limited regarding disease-specificity. Approach II uses the information from medications specific for a single disease and therefore can reach higher concordance scores. The strategies described in a detailed and reproducible manner are generally applicable in large studies and might be useful to extract as much information as possible from the available data.
Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 ...immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov , number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five 4% of 117 patients), pneumonitis (four 3%), and diarrhoea (three 3%). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding Bristol-Myers Squibb.
•The gas market is represented by a partial equilibrium model including market power.•We demonstrate that some prices and flows are not unique in general.•The gas flows to consumers are unique for ...traders exerting market power.•We conclude that the entire solution space has to be considered for interpretation.•We discuss the economical meaning of parameter value changes which enforce uniqueness.
Spatial partial equilibrium models incorporating conjectural variations are widely used to analyze the development of oligopolistic multi-agent markets, such as international energy and raw material markets. Although this model type can produce multiple equilibria under commonly used assumptions, to the best of our knowledge, the consequences for the interpretation of the model results have not yet been explored in detail. To this end, we derive a linear complementarity model for the gas market and discuss under which assumptions on the model structure a component of the solution is unique. In particular, we find that the gas flow between a trader and a consumer is unique whenever the trader is modeled to exert market power in the consumer’s market. We demonstrate our findings by computing the extreme points of the polyhedral solution space and show that erroneous conclusions could be drawn whenever only one (arbitrary) point in the solution space is picked for interpretation. Furthermore, we discuss whether economically meaningful parameter value changes exist which would enforce uniqueness in all components of the solution.
In this review article, we highlight recent advances in the field of solar energy conversion at a molecular level. We focus mainly on investigations regarding fullerenes as well as endohedral ...metallofullerenes in energy and/or electron donor-acceptor conjugates, hybrids, and arrays, but will also discuss several more advanced systems. Hereby, the mimicry of the fundamental processes occurring in natural photosynthesis, namely light harvesting (LH), energy transfer (EnT), reductive/oxidative electron transfer (ET), and catalysis (CAT), which serve as a blue print for the rational design of artificial photosynthetic systems, stand at the focalpoint. Importantly, the key processes in photosynthesis, that is, LH, EnT, ET, and CAT, define the structure of this review with the only further differentiation in terms of covalent and non-covalent systems. Fullerenes as well as endohedral metallofullerenes are chosen by virtue of their small reorganization energies in electron transfer processes, on the one hand, and their exceptional redox behaviour, on the other hand.
In the Fourth Industrial Revolution (4IR), STARA (smart technology, artificial intelligence, robotics, and algorithms) is predicted to replace a third of the jobs that exist today. Almost twice as ...many current work tasks will be handled by robots. It is forecast that by 2025, 85 million jobs may be displaced by a shift in the division of labor between humans and machines, while 97 million new roles may emerge that are more adapted to the new division of labor between humans, machines and algorithms. Industrial psychologists are playing an increasingly important role in the workplace due to these trends from a strategic intelligence perspective. The objective of this article is to present a critical review of industrial psychologists in future workplaces in the context of the 4IR - STARA. A competence model is posed for industrial psychologists to perform a strategic intelligence role in organizations in the 4IR.
Graphene single crystals with dimensions of up to 0.5 mm on a side were grown by low-pressure chemical vapor deposition in copper-foil enclosures using methane as a precursor. Low-energy electron ...microscopy analysis showed that the large graphene domains had a single crystallographic orientation, with an occasional domain having two orientations. Raman spectroscopy revealed the graphene single crystals to be uniform monolayers with a low D-band intensity. The electron mobility of graphene films extracted from field-effect transistor measurements was found to be higher than 4000 cm2 V−1 s−1 at room temperature.
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