Grazing Incidence Small Angle X-Ray Scattering (GISAXS) on Small Targets Using Large Beams

GISAXS is often used as a versatile tool for the contactless and destruction-free investigation of nanostructured surfaces. However, due to the shallow incidence angles, the footprint of the X-ray beam is significantly elongated, limiting GISAXS to samples with typical target lengths of several millimetres. For many potential applications, the production of large target areas is impractical, and the targets are surrounded by structured areas. Because the beam footprint is larger than the targets, the surrounding structures contribute parasitic scattering, burying the target signal. In this paper, GISAXS measurements of isolated as well as surrounded grating targets in Si substrates with line lengths from $50\,{\rm\mu m}$ down to $4\,{\rm\mu m}$ are presented. For the isolated grating targets, the changes in the scattering patterns due to the reduced target length are explained. For the surrounded grating targets, the scattering signal of a $15\,{\rm\mu m}\,\times\,15\,{\rm\mu m}$ target grating structure is separated from the scattering signal of $100\,{\rm\mu m}\,\times\,100\,{\rm\mu m}$ nanostructured surroundings by producing the target with a different orientation with respect to the predominant direction of the surrounding structures. The described technique allows to apply GISAXS, e.g. for characterization of metrology fields in the semiconductor industry, where up to now it has been considered impossible to use this method due to the large beam footprint

Time Series Prediction for Energy Consumption of Computer Numerical Control Axes Using Hybrid Machine Learning Models

The prediction of energy-related time series for computer numerical control (CNC) machine tool axes is an essential enabler for the shift towards autonomous and intelligent production. In particular, a precise prediction of energy consumption is needed to determine the environmental impact of a product and the optimization of its production. For this purpose, a novel approach for predicting high-frequency time series of numerically controlled axes based on the program code to be executed is presented. The method involves simulative preprocessing of the input NC code to determine each axis’s acceleration, velocity, and process force. Combined with the material removal rate, these variables are input for a machine learning (ML) model that delivers axis-specific high-frequency time series predictions. Compared to common approaches, it is thus possible to make predictions for the variable energy consumption of machine tools for any tool path or target resolution in the time domain. Experiments show that this approach achieves a high precision when a robust learning data basis is available. For the X-, Y-, and Z-axis, errors of 0.2%, −1.09%, and 0.09% for aircut and of 0.15%, −3.55%, and 0.08% for material removal can be achieved. The potentials for further improvement are identified systematically

Reconstructing Detailed Line Profiles of Lamellar Gratings from GISAXS Patterns with a Maxwell Solver

Laterally periodic nanostructures were investigated with grazing incidence small angle X-ray scattering (GISAXS) by using the diffraction patterns to reconstruct the surface shape. To model visible light scattering, rigorous calculations of the near and far field by numerically solving Maxwell's equations with a finite-element method are well established. The application of this technique to X-rays is still challenging, due to the discrepancy between incident wavelength and finite-element size. This drawback vanishes for GISAXS due to the small angles of incidence, the conical scattering geometry and the periodicity of the surface structures, which allows a rigorous computation of the diffraction efficiencies with sufficient numerical precision. To develop dimensional metrology tools based on GISAXS, lamellar gratings with line widths down to 55 nm were produced by state-of-the-art e-beam lithography and then etched into silicon. The high surface sensitivity of GISAXS in conjunction with a Maxwell solver allows a detailed reconstruction of the grating line shape also for thick, non-homogeneous substrates. The reconstructed geometrical line shape models are statistically validated by applying a Markov chain Monte Carlo (MCMC) sampling technique which reveals that GISAXS is able to reconstruct critical parameters like the widths of the lines with sub-nm uncertainty

Histological markers in nasal mucosa of patients with Alzheimer's disease

Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated, in these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease

Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis

Background Alcohol use during pregnancy is the direct cause of fetal alcohol syndrome (FAS). We aimed to estimate the prevalence of alcohol use during pregnancy and FAS in the general population and, by linking these two indicators, estimate the number of pregnant women that consumed alcohol during pregnancy per one case of FAS. Methods We began by doing two independent comprehensive systematic literature searches using multiple electronic databases for original quantitative studies that reported the prevalence in the general population of the respective country of alcohol use during pregnancy published from Jan 1, 1984, to June 30, 2014, or the prevalence of FAS published from Nov 1, 1973, to June 30, 2015, in a peer-reviewed journal or scholarly report. Each study on the prevalence of alcohol use during pregnancy was critically appraised using a checklist for observational studies, and each study on the prevalence of FAS was critically appraised by use of a method specifi cally designed for systematic reviews addressing questions of prevalence. Studies on the prevalence of alcohol use during pregnancy and/or FAS were omitted if they used a sample population not generalisable to the general population of the respective country, reported a pooled estimate by combining several studies, or were published in iteration. Studies that excluded abstainers were also omitted for the prevalence of alcohol use during pregnancy. We then did country-specifi c randomeff ects meta-analyses to estimate the pooled prevalence of these indicators. For countries with one or no empirical studies, we predicted prevalence of alcohol use during pregnancy using fractional response regression modelling and prevalence of FAS using a quotient of the average number of women who consumed alcohol during pregnancy per one case of FAS. We used Monte Carlo simulations to derive confi dence intervals for the country-specifi c point estimates of the prevalence of FAS. We estimated WHO regional and global averages of the prevalence of alcohol use during pregnancy and FAS, weighted by the number of livebirths per country. The review protocols for the prevalence of alcohol use during pregnancy (CRD42016033835) and FAS (CRD42016033837) are available on PROSPERO. Findings Of 23 470 studies identifi ed for the prevalence of alcohol use, 328 studies were retained for systematic review and meta-analysis; the search strategy for the prevalence of FAS yielded 11 110 studies, of which 62 were used in our analysis. The global prevalence of alcohol use during pregnancy was estimated to be 9·8% (95% CI 8·9–11·1) and the estimated prevalence of FAS in the general population was 14·6 per 10 000 people (95% CI 9·4–23·3). We also estimated that one in every 67 women who consumed alcohol during pregnancy would deliver a child with FAS, which translates to about 119 000 children born with FAS in the world every year. Interpretation Alcohol use during pregnancy is common in many countries and as such, FAS is a relatively prevalent alcohol-related birth defect. More eff ective prevention strategies targeting alcohol use during pregnancy and surveillance of FAS are urgently needed

Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from rheumatoid arthritis: a case report

<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, <it>C. neoformans </it>causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis.</p> <p>Case Presentation</p> <p>An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with <it>Cryptococcus neoformans</it>, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed.</p> <p>Conclusions</p> <p>Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.</p

Cross-sectional study on the characteristics of unrecorded alcohol consumption in nine newly independent states between 2013 and 2017

Objectives: As unrecorded alcohol use contributes to a substantial burden of disease, this study characterises this phenomenon in newly independent states (NIS) of the former Soviet Union with regard to the sources of unrecorded alcohol, and the proportion of unrecorded of total alcohol consumption. We also investigate associated sociodemographic characteristics and drinking patterns. Design: Cross-sectional data on overall and unrecorded alcohol use in the past 7 days from WHO STEPwise Approach to NCD Risk Factor Surveillance (STEPS) surveys. Descriptive statistics were calculated at the country level, hierarchical logistic and linear regression models were used to investigate sociodemographic characteristics and drinking patterns associated with using unrecorded alcohol. Setting: Nine NIS (Armenia, Azerbaijan, Belarus, Georgia, Kyrgyzstan, Republic of Moldova, Tajikistan, Turkmenistan and Uzbekistan) in the years 2013–2017. Participants: Nationally representative samples including a total of 36 259 participants. Results: A total of 6251 participants (19.7%; 95% CI 7.9% to 31.5%) reported alcohol consumption in the past 7 days, 2185 of which (35.1%; 95% CI 8.2% to 62.0%) reported unrecorded alcohol consumption with pronounced differences between countries. The population-weighted average proportion of unrecorded consumption in nine NIS was 8.7% (95% CI 5.9% to 12.4%). The most common type of unrecorded alcohol was home-made spirits, followed by home-made beer and wine. Older (45–69 vs 25–44 years) and unemployed (vs employed) participants had higher odds of using unrecorded alcohol. More nuanced sociodemographic differences were observed for specific types of unrecorded alcohol. Conclusions This contribution is the first to highlight both, prevalence and composition of unrecorded alcohol consumption in nine NIS. The observed proportions and sources of unrecorded alcohol are discussed in light of local challenges in policy implementation, especially in regard to the newly formed Eurasian Economic Union (EAEU), as some but not all NIS are in the EAEU

Highly efficient soft x-ray spectrometer for transient absorption spectroscopy with broadband table-top high harmonic sources

We present a novel soft x-ray spectrometer for ultrafast absorption spectroscopy utilizing table-top femtosecond high-order harmonic sources. Where most commercially available spectrometers rely on spherical variable line space gratings with a typical efficiency on the order of 3% in the first diffractive order, this spectrometer, based on a Hettrick–Underwood design, includes a reflective zone plate as a dispersive element. An improved efficiency of 12% at the N K-edge is achieved, accompanied by a resolving power of 890. The high performance of the soft x-ray spectrometer is further demonstrated by comparing nitrogen K-edge absorption spectra from calcium nitrate in aqueous solution obtained with our high-order harmonic source to previous measurements performed at the electron storage ring facility BESSY II

Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans