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BACKGROUND: An important window of opportunity for early-life exposures has been proposed for the development of atopic eczema and asthma.OBJECTIVE: However, it is unknown whether hay fever with a peak incidence around late school age to adolescence is similarly determined very early in life.METHODS: In the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort potentially relevant exposures such as farm milk consumption and exposure to animal sheds were assessed at multiple time points from infancy to age 10.5 years and classified by repeated measure latent class analyses (n [ 769). Fecal samples at ages 2 and 12 months were sequenced by 16S rRNA. Hay fever was defined by parent -reported symptoms and/or physician's diagnosis of hay fever in the last 12 months using questionnaires at 10.5 years.RESULTS: Farm children had half the risk of hay fever at 10.5 years (adjusted odds ratio [aOR] 0.50; 95% CI 0.31-0.79) than that of nonfarm children. Whereas early life events such as gut microbiome richness at 12 months (aOR 0.66; 95% CI 0.46-0.96) and exposure to animal sheds in the first 3 years of life (aOR 0.26; 95% CI 0.06-1.15) were determinants of hay fever, the continuous consumption of farm milk from infancy up to school age was necessary to exert the protective effect (aOR 0.35; 95% CI 0.17-0.72).CONCLUSIONS: While early life events determine the risk of subsequent hay fever, continuous exposure is necessary to achieve protection. These findings argue against the notion that only early life exposures set long-lasting trajectories. (c) 2022 The Authors. Published by Elsevier Inc

Parental exposures prior to conception might influence asthma and allergy risk in offspring. As occupational exposures are established risk factors for asthma and allergies, we investigated if parental occupational exposures prior to conception cause wheeze and eczema in offspring during the first year of life.We analysed data of 436 families from an offspring cohort based on a follow-up study of German participants of the International Study of Asthma and Allergies in Childhood (ISAAC). Offspring cohort data was collected between 2009 and 2019. Occupational exposures were based on participants' work histories and measured by a Job-Exposure-Matrix. We used Bayesian logistic regression models for analysis. Inference and confounder selection were based on directed acyclic graphs.In mothers, for both allergic and irritative occupational exposures prior to conception suggestive effects on offspring eczema during the first year of life were found (allergens: odds ratio (OR) 1.22, 95% compatibility interval (CI) 0.92-1.57; irritants: OR 1.36, 95% CI 0.99-1.77), while no relation with wheeze was suggested.Our results suggest that reduction of asthma-related occupational exposures might not only reduce the burden of disease for occupationally induced or aggravated asthma and allergies in employees but also in their children.

BackgroundDespite major advances in the development of targeted therapies, precision (immuno)oncology approaches for patients with colorectal cancer continue to lag behind other solid cancers. Functional precision oncology – a strategy that is based on perturbing primary tumor cells from cancer patients with drugs – could provide an alternate road forward to personalize treatment.MethodsWe extend here the functional precision oncology paradigm to measuring phosphoproteome landscapes using patient-derived organoids (PDOs). We first employed steady-state multi-omics (exome sequencing, RNA sequencing, and proteomics) and single-cell characterization of the PDOs. The PDOs were then perturbed with kinase inhibitors (MEKi, PI3Ki, mTORi, TBKi, BRAFi, and TAKi), and large-scale phosphoproteomics profiling using data-independent acquisition was carried out. Further, we used imaging mass-cytometry-based single-cell proteomic profiling of the primary tumors to characterize cellular composition of the tumor-microenvironment (TME) and to quantify heterocellular signaling crosstalk.ResultsWe show that kinase inhibitors induce profound off-target effects resulting in a crosstalk with oncogenic and immune-related pathways. Reconstruction of the topologies of the kinase networks revealed that the patient-specific rewiring of the central EGFR-RAS-MAPK network is unaffected by mutations. Moreover, we show non-genetic heterogeneity of the PDOs and patient- and inhibitor-specific upregulation of stemness and differentiation genes by kinase inhibitors. We complemented our functional profiling by spatial proteomics profiling of the primary tumors using imaging mass cytometry. We quantify spatial heterocellular crosstalk and tumor-immune cell interactions, showing an avoidance of PD1+ immune cells and PD-L1+ tumor cells.ConclusionsCollectively, we provide a multi-modal framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno)-oncology in colorectal cancer.

Objective Fragmentary myoclonus (FM) is a polysomnographic motor phenomenon of unknown clinical relevance. This study investigates FM prevalence, gender differences, sleep stage distribution and association with clinical factors using recently introduced advanced FM scoring criteria. Methods We analyzed polysomnographic recordings of 178 patients of a mixed sleep-disorder patient cohort. FM indices (FMI) of newly introduced 25 μV (FMI25) and standard 50 μV (FMI50) amplitude cut-offs were calculated. Results FMI25 and FMI50 were higher in men compared to women. FMI were higher during wakefulness and lower during S3 compared to all other sleep stages, with stronger effects in men compared to women. FMI25 was correlated with higher age, lower mean oxygen saturation, lower sleep efficiency, higher periodic limb movement (PLM) index, shorter sleep period time and higher arousal index. Linear regression showed that age predicted higher FMI25 in both males and females. Additionally, higher arousal index predicted higher FMI25 in women only. FMI were not associated with the presence of sleep-related breathing disorders. Conclusions We suggest FM represents a ubiquitous motor phenomenon occurring spontaneously during relaxed wakefulness and sleep, primarily in men and with advanced age. Significance In women, particularly FMI25 may be a surrogate marker for more frequent arousals and sleep fragmentation.

This paper focuses on the design of a novel path following control concept for fixed-wing aircraft, which systematically incorporates the nonlinearities of the flight dynamics. By introducing an acceleration based inner loop control, feedforward acceleration demands of nonlinear 3D paths can be directly taken into account. Furthermore, the nonlinear effects of airspeed, orientation, and gravity are considered separately by implementing a cascaded design and feedback linearization. As a result, robust performance of the path following control is achieved even for wind speeds in the order of the aircraft’s airspeed and path accelerations significantly higher than the gravitational acceleration. By further including direct lift control, a high-bandwidth vertical acceleration control is developed. Results of flight experiments show that the designed control concept is particularly beneficial in terms of the tracking performance for 3D paths, the incorporation of input constraints, the robustness against wind and turbulence effects, and the ease of implementation as well as the low computational complexity.

This paper explores the domestic and international effects of an increase in observed interest rates (conventional monetary policy) and expected interest rates (forward guidance). We find significant spillovers to a broad range of countries when both are subject to a tightening shock: Output growth and inflation decelerate and equity returns decline. Currencies of euro area neighboring countries tend to depreciate against the euro. A tightening forward guidance shock triggers more persistent effects on euro area and international interest rates. We find that international effects vary over the sample period when either interest rates are shocked.

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to beta-lactam antibiotics, while some strains are multi-drug resistant and may produce disease-causing toxins. Drug resistant strains are often responsible for chronic, persistent and recurrent infections, which pose a challenge for healthcare practitioners. Our study aimed to determine the prevalence of nasal MRSA and methicillin-resistant coagulase-negative staphylococci (MRCoNS) among school children in the Mariental community, southern Namibia. This was a cross-sectional study in the Mariental District. Nasal specimens (swabs) were collected from 272 randomly selected learners aged 6–14 years attending school in the area during the months of March, September and October 2016. Isolation and identification of staphylococci were performed using standard microbiological methods. Methicillin-resistant isolates were identified by their resistance towards cefoxitin (30 µg) using the Kirby-Bauer disk diffusion assay. Enterotoxin production among multi-drug resistant MRSA isolates was detected with a SET-RPLA toxin detection kit. Methicillin-resistant S. aureus was isolated from 48 (17.6%) learners and MRCoNS from only seven (2.6%). Methicillin-resistant S. aureus colonization was significantly higher (P = 0.003) in the age group 11–14 years than in the group 6–10 years. Among the 433 staphylococcal isolates screened for cefoxitin resistance, 51 (11.8%) were MRSA and seven (1.6%) were MRCoNS. From the 51 MRSA isolates, 22 (43.1%) were multi-drug resistant of which six were enterotoxigenic. This is the first report on MRSA and MRCoNS among school children in Namibia. The presence of multi-drug resistant and potentially virulent staphylococci among school children in Mariental, Namibia, is of concern. Self-infection by these bacteria poses various health risks for the children. It is recommended that school health programmes improve current hygiene practices. Frequent handwashing can prevent staphylococcal disease and spread of resistant strains among learners and the wider community.

Analysis of digital images by smartphone was used for copper quantification in sugarcane spirit (cachaca) samples through the formation of blue complex between copper and cuprizone. An experimental design was carried out to evaluate the best complexation reaction conditions. Moreover, different image acquisition procedures (external camera coupled to a smartphone or the smartphone camera) with different regions of interest sizes, distances in image acquisition, and concentration ranges of the calibration curve and the influence of processing the curve in univariate and multivariate modes, by PLS, were evaluated. The results obtained in three real samples and two spikes were compared with those of UV–Vis spectrophotometry, used as a reference method, and they show the potential of the proposed method for the accurate determination of copper. When compared to traditional techniques, the proposed method has the advantages of portability and low cost in addition to requiring a smaller amount of reagents.

In emotion recognition from speech, huge amounts of training material are needed for the development of classification engines. As most current corpora do not supply enough material, a combination of different datasets is advisable. Unfortunately, data recording is done differently and various emotion elicitation and emotion annotation methods are used. Therefore, a combination of corpora is usually not possible without further effort. The manuscript’s aim is to answer the question which corpora are similar enough to jointly be used as training material. A corpus similarity measure based on PCA-ranked features is presented and similar datasets are identified. To evaluate our method we used nine well-known benchmark corpora and automatically identified a sub-set of six most similar datasets. To test that the identified most similar six datasets influence the classification performance, we conducted several cross-corpora emotion recognition experiments comparing our identified six most similar datasets with other combinations. Our most similar sub-set outperforms all other combinations of corpora, the combination of all nine datasets as well as feature normalization techniques. Also influencing side-effects on the recognition rate were excluded. Finally, the predictive power of our measure is shown: increasing similarity score, expressing decreasing similarity, result in decreasing recognition rates. Thus, our similarity measure answers the question which corpora should be included into joint training.

Bacterium-host interactions are important for diverse ecological settings including pathogenicity and symbiosis. Electron cryotomography is a powerful method for studying the macromolecular complexes that mediate such interactions in situ. The main limitation of electron cryotomography is its restriction to relatively thin samples such as individual bacterial cells. Cryo-focused ion beam milling was recently proposed as a solution to the thickness limitation. This approach allows the artifact-free thinning of biological specimens for subsequent imaging in the transmission electron microscope. By enabling near-native imaging of bacteria inside their eukaryotic host, this combination of techniques promotes the integration of data from structural biology and infection biology. Therefore, electron cryotomography associated with cryo-focused ion beam milling holds great potential for establishing multiscale models of cell-cell interactions from the atomic, to the cellular and to the intercellular scale.

The Schinziophyton rautanenii tree is an important food source for many communities of the African continent. Oil extracted from the Manketti nut is of great economic value, due to its unique composition and properties. In this study, the physical and chemical characteristics of the oil obtained from three extraction methods – cold pressed, traditional and Soxhlet extraction – were investigated and compared. Oil yield of the nut was found to be 42.6 ± 0.84%. Good quality characteristics, including saponification values (184–189 mg KOH/g), iodine values (120–131 g/100 g), acid values (0.959–2.44 mg KOH/g) and peroxide values (1.80–3.98 meqO2/kg) were found for the Manketti nut oil. The total tocopherol content was in the range of 144–206 mg/100 g of oil, with γ-tocopherol as the dominant tocopherol. The oil was rich in conjugated fatty acids, α-eleostearic (9Z,11E,13E-octadecatrienoic acid) (24–36%) and linoleic acid (9Z,12Z-octadeca-9,12-dienoic acid) (31–32%), making it a potential candidate in the nutraceutical and cosmetics industry.

Vitality loss of trees caused by extreme weather conditions, drought stress or insect infestations, are expected to increase with ongoing climate change. The detection of vitality loss at an early stage is thus of vital importance for forestry and forest management to minimize ecological and economical damage. Remote sensing instruments are able to detect changes over large areas down to the level of individual trees. The scope of our study is to investigate whether it is possible to detect stress-related spectral changes at an early stage using hyperspectral sensors. For this purpose, two Norway spruce (Picea abies) forest stands, both different in age and maintenance, were monitored in the field over two vegetation periods. In parallel, time series of airborne hyperspectral remote sensing data were acquired. For each stand 70 trees were artificially stressed (ring-barked) and 70 trees were used as control trees. The data collected in south-eastern Germany consists of measurements at multiple times and at different scales: (1) crown conditions were visually assessed in the field (2) needle reflectance spectra were acquired in the laboratory using a FieldSpec spectrometer, and (3) hyperspectral airborne data (HySpex) were flown at 0.5 m spatial resolution. We aimed for a simultaneous data acquisition at the three levels. This unique data set was investigated whether any feature can be discriminated to detect vitality loss in trees at an early stage. Several spectral transformations were applied to the needle and tree crown spectra, such as spectral derivatives, vegetation indices and angle indices. All features were examined for their separability (ring-barked vs. control trees) with the Random Forest (RF) classification algorithm. As result, the younger, well maintained forest stand only showed minor changes over the 2-year period, whereas changes in the older forest stand were observable both in the needle and in the hyperspectral tree crown spectra, respectively. These changes could even be detected before changes were visible by field observations. The tree spectral reactions to ring-barking were first noticeable 11 months after ring-barking and 6 weeks before they were visible by field inspection. The most discriminative features for separating the two groups were the reflectance spectra and the spectral derivatives, over the VIs or angle indices. The tree crown spectra of the two groups could be separated by the RF classifier with a 79% overall accuracy at the beginning of the second vegetation period and 1 month later with 92% overall accuracy with high kappa index. The results clearly demonstrate the great potential of hyperspectral remote sensing in detecting early vitality changes of stressed trees.

Several studies report an important role of CD8(+) cytotoxic T-cells in atopy. Farm children show protection against atopy development, partly explained by CD4(+) T-cell subtypes. Additional effects of CD8(+) T-cells are unknown being investigated in this study within the PASTURE/EFRAIM birth cohort in PBMCs from farming and non-farming 6-year-old (N = 76) German children. CD3(+) CD8(+) CD25(+) T-cells were analyzed by flow cytometry. Genotyping of 17q21 locus-SNPs associated with childhood asthma was performed. No differences in CD8(+) T-cell subsets were seen between farmers and non-farmers regardless of asthma. Among farm children, asthmatics displayed increased CD3(+) CD8(low)(CD25(+)) T-cells compared to non-asthmatics. Asthmatic farm children exhibited a lower PI-induced stimulatory capacity of CD3(+) CD8(low)(CD25(+)) cells and a lower IFN-gamma secretion than non-asthmatic farm children. Among farm children with GSDMB and ORMDL3 risk alleles, asthmatics displayed higher CD3(+) CD8(low) cells than non-asthmatics. Our data indicates a specific role of CD8(low) T-cells in asthmatic farm children. (C) 2017 Elsevier Inc. All rights reserved.

This paper presents a path following control concept for elastic joint robots. A controller is designed using transverse feedback linearization and a parallel transport frame that is suitable for regular paths with parametrized fivefold continuously differentiable representation. Systematic application of the singular perturbation theory makes this concept also applicable to elastic joint robots with a larger number of degrees of freedom. A simulation example for a six-axis industrial robot shows the feasibility of the proposed approach and the advantages compared to classical trajectory tracking control.

Time is a crucial factor in the transport business. Besides the duration of the transport itself, also the loading and unloading of the goods is expected to be done as fast as possible to save valuable time and money. Amongst others, this holds true for container ships where the containers are usually loaded and unloaded by means of ship-to-shore gantry cranes. This scenario exemplarily motivates the investigations in this paper. Different methods are proposed for generating a trajectory for the load based on a geometric path connecting the loading and unloading position. As the path is usually just known right before the task has to begin, special emphasis lies on a fast calculation of the trajectory. The overall goal is to traverse the geometric path as fast as possible under the consideration of constraints for the gantry crane system. The optimal solution is calculated and serves as a reference for comparison reasons as the required computing time is usually rather large. Therefore, tailored methods for a fast calculation of the trajectory are developed. All the different approaches are evaluated and compared by means of representative test paths.

For the automation of certain industrial tasks, like the handling of deformable materials, force/torque sensors are frequently employed in robotic manipulators. This work investigates different signal processing strategies for a force sensor mounted on the end-effector of a biaxial gantry robot. For this, a suitable mathematical model of the manipulator is derived and analyzed. The merits and limitations of the proposed signal processing strategies are compared and validated by a number of experimental results.