Search

Aims: Neuronal hypersensitisation due to adenosine triphosphate‐dependent P2X3 receptor signalling plays a significant role in several disorders including chronic cough and endometriosis. This first‐in‐human study of eliapixant (BAY 1817080) investigated the tolerability, safety and pharmacokinetics (PK) of single doses of eliapixant, including the effect of food and coadministration with a CYP3A inhibitor on eliapixant relative bioavailability. Methods: In this randomised, double‐blind phase I study (NCT02817100), 88 healthy male subjects received single ascending doses of immediate‐release eliapixant (10–800 mg) tablets or placebo under fasted conditions, with food (low‐fat continental or high‐fat American breakfast) or with itraconazole (fasted state). PK parameters, dose proportionality, adverse events and taste assessments (taste strips; dysgeusia questionnaire) were evaluated. Results: Eliapixant had a long half‐life (23.5–58.9 h [fasted state]; 32.8–43.8 h [high‐fat breakfast]; 38.9–46.0 h [low‐fat breakfast]). Less than dose‐proportional increases in maximum plasma concentrations (Cmax) and area under the concentration–time curve from time 0 to infinity (AUC[0–inf]) were observed with ascending eliapixant doses. We observed a pronounced food effect with the high‐fat breakfast (4.1‐fold increased Cmax; 2.7‐fold increased AUC[0–inf]), a smaller food effect with the low‐fat breakfast and a mild‐to‐moderate effect of itraconazole coadministration on eliapixant (1.1–1.2‐fold increased Cmax; 1.7‐fold increased AUC from 0 to 72 h). Eliapixant was well tolerated with minimal impact on taste perception. Conclusion: The PK profile, particularly the long half‐life, and favourable tolerability with no taste‐related adverse events, supports the further development of eliapixant in disorders with underlying P2X3 receptor‐mediated neuronal hypersensitisation. [ABSTRACT FROM AUTHOR]

This article seeks to reflect upon the place of resistance in a conceptual-theoretical sense, hereto articulating so called critical theory of society, based upon diagnosis brought forward specially by Max Horkheimer and Theodor W. Adorno, and the social theory of Lélia Gonzalez. By rooting its viewpoint in these two theoretical perspectives, conceived in very different historical and social contexts, I aim to address how they complement themselves and, as such, enhance the critical view on contemporary authoritarian manifestations. Notwithstanding the various changes taking place during the last decades, it thus presupposes that a number of key elements are constitutive of how the forms of repression and marginalization express themselves in capitalist societies, (re)producing an array of inequalities, foremost those of ethnic and racial kind. Hence, fostering resistance remains a vital quality to compose the horizon of intellectual practice of the social sciences. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to assess the ability of semi-automatically extracted magnetic resonance imaging (MRI)–based radiomic features from tibial subchondral bone to distinguish between knees without and with osteoarthritis. Methods: The right knees of 665 females from the population-based Rotterdam Study scanned with 1.5T MRI were analyzed. A fast imaging employing steady-state acquisition sequence was used for the quantitative bone analyses. Tibial bone was segmented using a method that combines multi-atlas and appearance models. Radiomic features related to the shape and texture were calculated from six volumes of interests (VOIs) in the proximal tibia. Machine learning–based Elastic Net models with 10-fold cross-validation were used to distinguish between knees without and with MRI Osteoarthritis Knee Score (MOAKS)–based tibiofemoral osteoarthritis. Performance of the covariate (age and body mass index), image features, and combined covariate + image features models were assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: Of 665 analyzed knees, 76 (11.4%) had osteoarthritis. An ROC AUC of 0.68 (95% confidence interval (CI): 0.60–0.75) was obtained using the covariate model. The image features model yielded an ROC AUC of 0.80 (CI: 0.73–0.87). The model that combined image features from all VOIs and covariates yielded an ROC AUC of 0.80 (CI: 0.73–0.87). Conclusion: Our results suggest that radiomic features are useful imaging biomarkers of subchondral bone for the diagnosis of osteoarthritis. An advantage of assessing bone on MRI instead of on radiographs is that other tissues can be assessed simultaneously. Key Points: • Subchondral bone plays a role in the osteoarthritis disease processes. • MRI radiomics is a potential method for quantifying changes in subchondral bone. • Semi-automatically extracted radiomic features of tibia differ between subjects without and with osteoarthritis. [ABSTRACT FROM AUTHOR]

To improve image quality of multi-contrast imaging with the proposed Autocalibrated Parallel Imaging Reconstruction for Extended Multi-Contrast Imaging (APIR4EMC). APIR4EMC reconstructs multi-contrast images in an autocalibrated parallel imaging reconstruction framework by adding contrasts as virtual coils. Compensation of signal evolution along the echo train of different contrasts is performed to improve signal prediction for missing samples. As a proof of concept, we performed prospectively accelerated phantom and in-vivo brain acquisitions with T1, T1-fat saturated (Fatsat), T2, PD, and FLAIR contrasts. The k-space sampling patterns of these acquisitions were jointly optimized. Images were jointly reconstructed with the proposed APIR4EMC method as well as individually with GRAPPA. Root mean square error (RMSE) to fully sampled reference images and g-factor maps were computed for both methods in the phantom experiment. Visual evaluation was performed in the in-vivo experiment. Compared to GRAPPA, APIR4EMC reduced artifacts and improved SNR of the reconstructed images in the phantom acquisitions. Quantitatively, APIR4EMC substantially reduced noise amplification (g-factor) as well as RMSE compared to GRAPPA. Signal evolution compensation reduced artifacts. In the in-vivo experiments, 1 mm 3 isotropic 3D images with contrasts of T1, T1-Fatsat, T2, PD, and FLAIR were acquired in as little as 7.5 min with the acceleration factor of 9. Reconstruction quality was consistent with the phantom results. Compared to single contrast reconstruction with GRAPPA, APIR4EMC reduces artifacts and noise amplification in accelerated multi-contrast imaging. [ABSTRACT FROM AUTHOR]

Opto-electronic device simulation of thin-film silicon solar cells requires a set of many input parameters for the electronic properties of amorphous and microcrystalline silicon. In this paper, a systematic determination of these is performed by inverse modeling and particle swarm optimization with experimental and simulated current-voltage characteristics of amorphous and microcrystalline silicon pin diodes, both in the dark and under illumination. The parameters are validated by additional experiments and simulations of the temperature-dependent dark current, of spectrally selective illumination, and of the external quantum efficiency of the amorphous and microcrystalline silicon diode, respectively. The validation of the input parameters is complemented by simulation of a tandem solar cell with the amorphous and the microcrystalline silicon input parameters. Simulation and experiment (spectrally dependent current-voltage characteristics and external quantum efficiency) of such a tandem solar cell show good agreement. Sensitivity studies on different sets of input parameters for the inverse modeling process are also presented. [ABSTRACT FROM AUTHOR]

Quantitative MRI methods that estimate multiple physical parameters simultaneously often require the fitting of a computational complex signal model defined through the Bloch equations. Repeated Bloch simulations can be avoided by matching the measured signal with a precomputed signal dictionary on a discrete parameter grid (i.e. lookup table) as used in MR Fingerprinting. However, accurate estimation requires discretizing each parameter with a high resolution and consequently high computational and memory costs for dictionary generation, storage, and matching. Here, we reduce the required parameter resolution by approximating the signal between grid points through B-spline interpolation. The interpolant and its gradient are evaluated efficiently which enables a least-squares fitting method for parameter mapping. The resolution of each parameter was minimized while obtaining a user-specified interpolation accuracy. The method was evaluated by phantom and in-vivo experiments using fully-sampled and undersampled unbalanced (FISP) MR fingerprinting acquisitions. Bloch simulations incorporated relaxation effects $(\boldsymbol {T}_{\boldsymbol {1}},\boldsymbol {T}_{\boldsymbol {2}})$ , proton density $\left ({\boldsymbol {PD} }\right)$ , receiver phase ($\boldsymbol {\varphi }_{\boldsymbol {0}}$), transmit field inhomogeneity ($\boldsymbol {B}_{\boldsymbol {1}}^{\boldsymbol {+}}$), and slice profile. Parameter maps were compared with those obtained from dictionary matching, where the parameter resolution was chosen to obtain similar signal (interpolation) accuracy. For both the phantom and the in-vivo acquisition, the proposed method approximated the parameter maps obtained through dictionary matching while reducing the parameter resolution in each dimension ($\boldsymbol {T}_{\boldsymbol {1}},\boldsymbol {T}_{\boldsymbol {2}},\boldsymbol {B}_{\boldsymbol {1}}^{\boldsymbol {+}}$) by – on average – an order of magnitude. In effect, the applied dictionary was reduced from $1.47GB$ to $464KB$. Furthermore, the proposed method was equally robust against undersampling artifacts as dictionary matching. Dictionary fitting with B-spline interpolation reduces the computational and memory costs of dictionary-based methods and is therefore a promising method for multi-parametric mapping. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) is the most common musculoskeletal disease without a cure, and current treatment options are limited to symptomatic relief. Prediction of OA progression is a very challenging and timely issue, and it could, if resolved, accelerate the disease modifying drug development and ultimately help to prevent millions of total joint replacement surgeries performed annually. Here, we present a multi-modal machine learning-based OA progression prediction model that utilises raw radiographic data, clinical examination results and previous medical history of the patient. We validated this approach on an independent test set of 3,918 knee images from 2,129 subjects. Our method yielded area under the ROC curve (AUC) of 0.79 (0.78–0.81) and Average Precision (AP) of 0.68 (0.66–0.70). In contrast, a reference approach, based on logistic regression, yielded AUC of 0.75 (0.74–0.77) and AP of 0.62 (0.60–0.64). The proposed method could significantly improve the subject selection process for OA drug-development trials and help the development of personalised therapeutic plans. [ABSTRACT FROM AUTHOR]

We have measured the subgap optical absorption of undoped microcrystalline silicon samples with photothermal deflection spectroscopy and compared it with the spin density measured by electron spin resonance. The material was prepared using the hot wire chemical vapor deposition technique with a broad range of deposition parameters, yielding materials with a wide variety of structural, optical, and electronic properties. A nearly linear correlation between the spin densities and the subgap absorption coefficient at photon energy of 0.7 eV over three orders of magnitude indicates that the optical absorption in this region is due to the dominating paramagnetic defects, likely dangling bonds. However, the structural composition of the material, determined by Raman spectroscopy, has also some influence on the optical and electronic properties, which leads to some deviation from a straightforward relationship between optical absorption and spin or defect density. [ABSTRACT FROM AUTHOR]

Microcrystalline silicon (μc-Si:H) of superior quality can be prepared using the hot-wire chemical-vapor deposition method (HWCVD). At a low substrate temperature (TS) of 185 °C excellent material properties and solar cell performance were obtained with spin densities of 6×1015 cm-3 and solar cell efficiencies up to 9.4%, respectively. In this study we have systematically investigated the influence of various deposition parameters on the deposition rate and the material properties. For this purpose, thin films and solar cells were prepared at specific substrate and filament temperatures and deposition pressures (pD), covering the complete range from amorphous to highly crystalline material by adjusting the silane concentration. The influence of these deposition parameters on the chemical reactions at the filament and in the gas phase qualitatively explains the behavior of the structural composition and the formation of defects. In particular, we propose that the deposition rate is determined by the production of reactive species at the filament and a particular atomic-hydrogen-to-silicon ratio is found at the microcrystalline/amorphous transition. The structural, optical, and electronic properties were studied using Raman and infrared spectroscopies, optical-absorption measurements, electron-spin resonance, and dark and photoconductivities. These experiments show that higher TS and pD lead to a deterioration of the material quality, i.e., much higher defect densities, oxygen contaminations, and SiH absorption at 2100 cm-1. Similar to plasma enhanced chemical-vapor deposition material, μc-Si:H solar cells prepared with HW i layers show increasing open circuit voltages (Voc) with increasing silane concentration and best performance is achieved near the transition to amorphous growth. Such solar cells prepared at low TS exhibit very high Voc up to 600 mV and fill factors above 70% with i layers prepared by HWCVD. [ABSTRACT FROM AUTHOR]

This study evaluated and characterized the pharmacological activity of the orally administered interleukin‐1 receptor‐associated kinase 4 (IRAK4) inhibitors BAY1834845 (zabedosertib) and BAY1830839 in healthy male volunteers. Participants received one of either IRAK4 inhibitors or a control treatment (prednisolone 20 mg or placebo) twice daily for 7 days. Localized skin inflammation was induced by topical application of imiquimod (IMQ) cream for 3 days, starting at Day 3 of treatment. The inflammatory response was evaluated by laser speckle contrast imaging (skin perfusion) and multispectral imaging (erythema). At Day 7, participants received 1 ng/kg intravenous lipopolysaccharide (LPS). Circulating inflammatory proteins, leukocyte differentiation, acute phase proteins, and clinical parameters were evaluated before and after the systemic LPS challenge. Treatment with BAY1834845 significantly reduced the mean IMQ‐induced skin perfusion response (geometric mean ratio [GMR] vs. placebo: 0.69 for BAY1834845, 0.70 for prednisolone; both p < 0.05). Treatment with BAY1834845 and BAY1830839 significantly reduced IMQ‐induced erythema (GMR vs. placebo: 0.75 and 0.83, respectively, both p < 0.05; 0.86 for prednisolone, not significant). Both IRAK4 inhibitors significantly suppressed the serum TNF‐α and IL‐6 responses (≥80% suppression vs. placebo, p < 0.05) and inhibited C‐reactive protein, procalcitonin, and IL‐8 responses to intravenous LPS. This study demonstrated the pharmacological effectiveness of BAY1834845 and BAY1830839 in suppressing systemically and locally induced inflammatory responses in the same range as prednisolone, underlining the potential value of these IRAK4 inhibitors as future therapies for dermatological or other immune‐mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Image registration is an important task in medical image analysis. Whereas most methods are designed for the registration of two images (pairwise registration), there is an increasing interest in simultaneously aligning more than two images using groupwise registration. Multimodal registration in a groupwise setting remains difficult, due to the lack of generally applicable similarity metrics. In this work, a novel similarity metric for such groupwise registration problems is proposed. The metric calculates the sum of the conditional entropy between each image in the group and a representative template image constructed iteratively using principal component analysis. The proposed metric is validated in extensive experiments on synthetic and intrasubject clinical image data. These experiments showed equivalent or improved registration accuracy compared to other state-of-the-art (dis)similarity metrics and improved transformation consistency compared to pairwise mutual information. [ABSTRACT FROM AUTHOR]

A study was performed to investigate the effect of an intravaginally administered antimycotic, an antibiotic, and a spermicide plus the co-usage of tampons on the pharmacokinetics (PK) of levonorgestrel (LNG) and anastrozole (ATZ) administered as an intravaginal ring (IVR) releasing 1050 μg ATZ per day and 40 μg LNG per day. In this parallel-group, randomized, open-label study, healthy premenopausal women received an IVR as the main treatment. Comedications were administered on 3 consecutive evenings during treatment with IVR on days 9-11 (group A, 400 mg miconazole; group B, 100 mg clindamycin; group C, 75 mg nonoxynol-9); tampon co-usage (group D) was performed on days 20-23. The primary PK parameter was the average plasma concentration (Cav,ss) of ATZ and LNG at defined intervals, mainly prior to, during, and up to 7 days after the start of comedication. Fifty-two subjects were included, and at least 11 subjects per group completed the treatments. Overall, the medications and comedications were safe and well tolerated. Very similar ATZ and LNG plasma levels were observed across all groups. The calculated ratios of Cav,ss confirmed the absence of PK interactions because all relevant point estimates and 90% confidence intervals were within the range of 0.800-1.250, which is typically used in bioequivalence studies. These results demonstrate the absence of PK interactions between ATZ/LNG released from IVR and the tested antibiotic, antimycotic, spermicide, and tampons. Therefore, no restrictions for the use of the IVR are needed to continue the clinical program intended to treat endometriosis symptoms. [ABSTRACT FROM AUTHOR]

This article aims to evaluate traits of "critical systems theory" (Kritische Systemtheorie). Through delineating the main aspects of this debate, exposes immanent limits put to its conception of critique and its sketch as a theory of society, hence taking up critical counterpoints anchored in Germany and Brazil. Thus one identifies original contributions and insufficiencies of this theoretical view, closing with some brief considerations about its relation to the center-periphery dynamics. [ABSTRACT FROM AUTHOR]

Sparse representations classification (SRC) is a powerful technique for pixelwise classification of images and it is increasingly being used for a wide variety of image analysis tasks. The method uses sparse representation and learned redundant dictionaries to classify image pixels. In this empirical study we propose to further leverage the redundancy of the learned dictionaries to achieve a more accurate classifier. In conventional SRC, each image pixel is associated with a small patch surrounding it. Using these patches, a dictionary is trained for each class in a supervised fashion. Commonly, redundant/overcomplete dictionaries are trained and image patches are sparsely represented by a linear combination of only a few of the dictionary elements. Given a set of trained dictionaries, a new patch is sparse coded using each of them, and subsequently assigned to the class whose dictionary yields the minimum residual energy. We propose a generalization of this scheme. The method, which we call multiple sparse representations classification (mSRC), is based on the observation that an overcomplete, class specific dictionary is capable of generating multiple accurate and independent estimates of a patch belonging to the class. So instead of finding a single sparse representation of a patch for each dictionary, we find multiple, and the corresponding residual energies provides an enhanced statistic which is used to improve classification. We demonstrate the efficacy of mSRC for three example applications: pixelwise classification of texture images, lumen segmentation in carotid artery magnetic resonance imaging (MRI), and bifurcation point detection in carotid artery MRI. We compare our method with conventional SRC, K-nearest neighbor, and support vector machine classifiers. The results show that mSRC outperforms SRC and the other reference methods. In addition, we present an extensive evaluation of the effect of the main mSRC parameters: patch size, dictionary size, and sparsity level. [ABSTRACT FROM AUTHOR]

In this work we present a framework for reliably detecting significant differences in quantitative magnetic resonance imaging and evaluate it with diffusion tensor imaging (DTI) experiments. As part of this framework we propose a new spatially regularized maximum likelihood estimator that simultaneously estimates the quantitative parameters and the spatially-smoothly-varying noise level from the acquisitions. The noise level estimation method does not require repeated acquisitions. We show that the amount of regularization in this method can be set a priori to achieve a desired coefficient of variation of the estimated noise level. The noise level estimate allows the construction of a Cramér-Rao-lower-bound based test statistic that reliably assesses the significance of differences between voxels within a scan or across different scans. We show that the regularized noise level estimate improves upon existing methods and results in a substantially increased precision of the uncertainty estimates of the DTI parameters. It enables correct specification of the null distribution of the test statistic and with it the test statistic obtains the highest sensitivity and specificity. The source code of the estimation framework, test statistic and experiment scripts are made available to the community. [ABSTRACT FROM AUTHOR]

• We evaluated grand challenges on machine learning and neuroimaging in dementia. • The seven challenges were complementary regarding clinical questions and tasks. • Statistical analysis of factors improving performance could improve future challenges. • Impact would increase by clinical questions and data beyond Alzheimer's disease. • Grand challenges provide an opportunity for cross-cohort performance evaluation. Machine learning methods exploiting multi-parametric biomarkers, especially based on neuroimaging, have huge potential to improve early diagnosis of dementia and to predict which individuals are at-risk of developing dementia. To benchmark algorithms in the field of machine learning and neuroimaging in dementia and assess their potential for use in clinical practice and clinical trials, seven grand challenges have been organized in the last decade: MIRIAD (2012), Alzheimer's Disease Big Data DREAM (2014), CADDementia (2014), Machine Learning Challenge (2014), MCI Neuroimaging (2017), TADPOLE (2017), and the Predictive Analytics Competition (2019). Based on two challenge evaluation frameworks, we analyzed how these grand challenges are complementing each other regarding research questions, datasets, validation approaches, results and impact. The seven grand challenges addressed questions related to screening, clinical status estimation, prediction and monitoring in (pre-clinical) dementia. There was little overlap in clinical questions, tasks and performance metrics. Whereas this aids providing insight on a broad range of questions, it also limits the validation of results across challenges. The validation process itself was mostly comparable between challenges, using similar methods for ensuring objective comparison, uncertainty estimation and statistical testing. In general, winning algorithms performed rigorous data pre-processing and combined a wide range of input features. Despite high state-of-the-art performances, most of the methods evaluated by the challenges are not clinically used. To increase impact, future challenges could pay more attention to statistical analysis of which factors (i.e., features, models) relate to higher performance, to clinical questions beyond Alzheimer's disease, and to using testing data beyond the Alzheimer's Disease Neuroimaging Initiative. Grand challenges would be an ideal venue for assessing the generalizability of algorithm performance to unseen data of other cohorts. Key for increasing impact in this way are larger testing data sizes, which could be reached by sharing algorithms rather than data to exploit data that cannot be shared. Given the potential and lessons learned in the past ten years, we are excited by the prospects of grand challenges in machine learning and neuroimaging for the next ten years and beyond. [ABSTRACT FROM AUTHOR]

• We propose a theoretical metric to evaluate undersampling patterns for Q-MRI scans. • The metric was verified with prospectively undersampled scans for mapping T1 and T2. • Good patterns for Q-MRI scans could be obtained by low-discrepancy sampling. [Display omitted] To realize Quantitative MRI (QMRI) with clinically acceptable scan time, acceleration factors achieved by conventional parallel imaging techniques are often inadequate. Further acceleration is possible using model-based reconstruction. We propose a theoretical metric called TEUSQA: Time Efficiency for UnderSampled QMRI Acquisitions to inform sequence design and sample pattern optimisation. TEUSQA is designed for a particular class of reconstruction techniques that directly estimate tissue parameters, possibly using prior information to regularize the estimation. TEUSQA can be used to evaluate undersampling patterns for multi-contrast QMRI sequences targeting any tissue parameter. To verify the time efficiency predicted by TEUSQA, we performed Monte Carlo simulations and an accelerated parameter mapping with two sequences (Inversion prepared fast spin echo for T 1 and T 2 mapping and 3D GRASE for T 2 and B0 inhomogeneity mapping). Using TEUSQA, we assessed several ways to generate undersampling patterns in silico , providing insight into the relation between sample distribution and time efficiency for different acceleration factors. The time efficiency predicted by TEUSQA was within 15% of that observed in the Monte Carlo simulations and the prospective acquisition experiment. The assessment of undersampling patterns showed that a class of good patterns could be obtained by low-discrepancy sampling. We believe that TEUSQA offers a valuable instrument for developers of novel QMRI sequences pushing the boundaries of acceleration to achieve clinically feasible protocols. Finally, we applied a time-efficient undersampling pattern selected using TEUSQA for a 32-fold accelerated scan to map T 1 & T 2 mapping of a healthy volunteer. [ABSTRACT FROM AUTHOR]

Purpose: Treatments like radiotherapy and focused ultrasound in the abdomen require accurate motion tracking, in order to optimize dosage delivery to the target and minimize damage to critical structures and healthy tissues around the target. 4D ultrasound is a promising modality for motion tracking during such treatments. In this study, the authors evaluate the accuracy of motion tracking in the liver based on deformable registration of 4D ultrasound images. Methods: The offline analysis was performed using a nonrigid registration algorithm that was specifically designed for motion estimation from dynamic imaging data. The method registers the entire 4D image data sequence in a groupwise optimization fashion, thus avoiding a bias toward a specifically chosen reference time point. Three healthy volunteers were scanned over several breathing cycles (12 s) from three different positions and angles on the abdomen; a total of nine 4D scans for the three volunteers. Well-defined anatomic landmarks were manually annotated in all 96 time frames for assessment of the automatic algorithm. The error of the automatic motion estimation method was compared with interobserver variability. The authors also performed experiments to investigate the influence of parameters defining the deformation field flexibility and evaluated how well the method performed with a lower temporal resolution in order to establish the minimum frame rate required for accurate motion estimation. Results: The registration method estimated liver motion with an error of 1 mm (75% percentile over all datasets), which was lower than the interobserver variability of 1.4 mm. The results were only slightly dependent on the degrees of freedom of the deformation model. The registration error increased to 2.8 mm with an eight times lower temporal resolution. Conclusions: The authors conclude that the methodology was able to accurately track the motion of the liver in the 4D ultrasound data. The authors believe that the method has potential in interventions on moving abdominal organs such as MR or ultrasound guided focused ultrasound therapy and radiotherapy, pending the method is enabled to run in real-time. The data and the annotations used for this study are made publicly available for those who would like to test other methods on 4D liver ultrasound data. [ABSTRACT FROM AUTHOR]

Purpose: To introduce a semiautomatic algorithm to perform the registration of free-hand B-Mode ultrasound (US) and magnetic resonance imaging (MRI) of the carotid artery. Methods: The authors' approach combines geometrical features and intensity information. The only user interaction consists of placing three seed points in US and MRI. First, the lumen centerlines are used as landmarks for point based registration. Subsequently, in a joint optimization the distance between centerlines and the dissimilarity of the image intensities is minimized. Evaluation is performed in left and right carotids from six healthy volunteers and five patients with atherosclerosis. For the validation, the authors measure the Dice similarity coefficient (DSC) and the mean surface distance (MSD) between carotid lumen segmentations in US and MRI after registration. The effect of several design parameters on the registration accuracy is investigated by an exhaustive search on a training set of five volunteers and three patients. The optimum configuration is validated on the remaining images of one volunteer and two patients. Results: On the training set, the authors achieve an average DSC of 0.74 and a MSD of 0.66 mm on volunteer data. For the patient data, the authors obtain a DSC of 0.77 and a MSD of 0.69 mm. In the independent set composed of patient and volunteer data, the DSC is 0.69 and the MSD is 0.87 mm. The experiments with different design parameters show that nonrigid registration outperforms rigid registration, and that the combination of intensity and point information is superior to approaches that use intensity or points only. Conclusions: The proposed method achieves an accurate registration of US and MRI, and may thus enable multimodal analysis of the carotid plaque. [ABSTRACT FROM AUTHOR]

Abstract: As a result from the development of silicon thin-film solar cells that had been conducted at Applied Materials over the last few years, we present a new kind of microcrystalline silicon oxide (μc-SiO x :H) based p-layer for the application in amorphous/microcrystalline (a-Si:H/μc-Si:H) tandem solar cells on ZnO substrates. The refractive index of this p-layer can be adjusted in the range 2–3.5 and therefore serves as a refractive index matching layer between ZnO (n∼2) and silicon (n∼4). By applying such a layer the reflection of solar cells can be reduced to 3%. This results in a significant short circuit current increase in thin-film solar cells. As a follow up to the recently published results of large area thin film silicon modules by us , we describe in this paper in detail the material properties of this new silicon oxide p-layer, the optimization of electrical and optical properties in solar cells and also the impact on the light induced degradation of a-Si/μc-Si tandem junction cells. [Copyright &y& Elsevier]

Abstract: Recently, Applied Materials has demonstrated the ability to manufacture large area a-Si/μc-Si thin film modules with total area efficiencies of 10% and above. Reducing the production costs is now the key objective for an economic success of this technology. Decreasing the absorber layer thickness or increasing the deposition rate can reduce the cost significantly because the PECVD deposition of the silicon layers is one of the main cost contributors. But this would also reduce the conversion efficiency of amorphous/microcrystalline tandem cells (a-Si/μc-Si TJ cells). Therefore, optimizing TJ cells for maximal productivity requires a careful balancing of layer thicknesses and deposition rates. In this paper we studied the impact of deposition rates and absorber layer thicknesses for top and bottom cells. The reduction of the bottom cell (BC) thickness from 2μm to less than 1μm showed only a small impact on the stabilized module efficiency while having a big impact on the productivity of a production line. The influence of the top cell (TC) deposition rate on the other hand results in a big decrease of the efficiency while having only a small impact on the line output. 10.2% stable mini-module efficiency could be achieved with 900nm BC thickness, reducing the deposition time by 50%. [Copyright &y& Elsevier]

The article offers information on a medical research in which long term outcome of patients with steroid-refractory acute intestinal graft versus host disease after treatment with pentostatin was seen. It is stated that acute graft-versus-host disease (aGvHD) of the gastrointestinal tract is a major complication after allogeneic stem cell transplantation. It was concluded that the outcome of patients who fail firstline therapy with steroids is poor and no standard therapy has been developed.

From the clinical point of view, it is important to recognize residents’ level of expertise with regard to basic psychomotor skills. For that reason, surgeons and surgical organizations (e.g., Acreditation Council for Graduate Medical Education, ACGME) are calling for assessment tools that credential residents as technically competent. Currently, no method is universally accepted or recommended for classifying residents as “experienced,” “intermediates,” or “novices” according to their technical abilities. This study introduces a classification method for recognizing residents’ level of experience in laparoscopic surgery based on psychomotor laparoscopic skills alone. For this study, 10 experienced residents (>100 laparoscopic procedures performed), 10 intermediates (10–100 procedures performed), and 11 novices (no experience) performed four tasks in a box trainer. The movements of the laparoscopic instruments were recorded with the TrEndo tracking system and analyzed using six motion analysis parameters (MAPs). The MAPs of all participants were submitted to principal component analysis (PCA), a data reduction technique. The scores of the first principal components were used to perform linear discriminant analysis (LDA), a classification method. Performance of the LDA was examined using a leave-one-out cross-validation. Of 31 participants, 23 were classified correctly with the proposed method, with 7 categorized as experienced, 7 as intermediates, and 9 as novices. The proposed method provides a means to classify residents objectively as experienced, intermediate, or novice surgeons according to their basic laparoscopic skills. Due to the simplicity and generalizability of the introduced classification method, it is easy to implement in existing trainers. [ABSTRACT FROM AUTHOR]

Medical image registration is an important task in medical image processing. It refers to the process of aligning data sets, possibly from different modalities (e.g., magnetic resonance and computed tomography), different time points (e.g., follow-up scans), and/or different subjects (in case of population studies). A large number of methods for image registration are described in the literature. Unfortunately, there is not one method that works for all applications. We have therefore developed elastix, a publicly available computer program for intensity-based medical image registration. The software consists of a collection of algorithms that are commonly used to solve medical image registration problems. The modular design of elastix allows the user to quickly configure, test, and compare different registration methods for a specific application. The command-line interface enables automated processing of large numbers of data sets, by means of scripting. The usage of elastix for comparing different registration methods is illustrated with three example experiments, in which individual components of the registration method are varied. [ABSTRACT FROM AUTHOR]

We present a stochastic gradient descent optimisation method for image registration with adaptive step size prediction. The method is based on the theoretical work by Plakhov and Cruz (J. Math. Sci. 120(1):964–973, ). Our main methodological contribution is the derivation of an image-driven mechanism to select proper values for the most important free parameters of the method. The selection mechanism employs general characteristics of the cost functions that commonly occur in intensity-based image registration. Also, the theoretical convergence conditions of the optimisation method are taken into account. The proposed adaptive stochastic gradient descent (ASGD) method is compared to a standard, non-adaptive Robbins-Monro (RM) algorithm. Both ASGD and RM employ a stochastic subsampling technique to accelerate the optimisation process. Registration experiments were performed on 3D CT and MR data of the head, lungs, and prostate, using various similarity measures and transformation models. The results indicate that ASGD is robust to these variations in the registration framework and is less sensitive to the settings of the user-defined parameters than RM. The main disadvantage of RM is the need for a predetermined step size function. The ASGD method provides a solution for that issue. [ABSTRACT FROM AUTHOR]

An automatic method for delineating the prostate (including the seminal vesicles) in three-dimensional magnetic resonance scans is presented. The method is based on nonrigid registration of a set of prelabeled atlas images. Each atlas image is nonrigidly registered with the target patient image. Subsequently, the deformed atlas label images are fused to yield a single segmentation of the patient image. The proposed method is evaluated on 50 clinical scans, which were manually segmented by three experts. The Dice similarity coefficient (DSC) is used to quantify the overlap between the automatic and manual segmentations. We investigate the impact of several factors on the performance of the segmentation method. For the registration, two similarity measures are compared: Mutual information and a localized version of mutual information. The latter turns out to be superior (median ΔDSC≈0.02, p<0.01 with a paired two-sided Wilcoxon test) and comes at no added computational cost, thanks to the use of a novel stochastic optimization scheme. For the atlas fusion step we consider a majority voting rule and the “simultaneous truth and performance level estimation” algorithm, both with and without a preceding atlas selection stage. The differences between the various fusion methods appear to be small and mostly not statistically significant (p>0.05). To assess the influence of the atlas composition, two atlas sets are compared. The first set consists of 38 scans of healthy volunteers. The second set is constructed by a leave-one-out approach using the 50 clinical scans that are used for evaluation. The second atlas set gives substantially better performance (ΔDSC=0.04,p<0.01), stressing the importance of a careful atlas definition. With the best settings, a median DSC of around 0.85 is achieved, which is close to the median interobserver DSC of 0.87. The segmentation quality is especially good at the prostate-rectum interface, where the segmentation error remains below 1 mm in 50% of the cases and below 1.5 mm in 75% of the cases. [ABSTRACT FROM AUTHOR]

A popular technique for nonrigid registration of medical images is based on the maximization of their mutual information, in combination with a deformation field parameterized by cubic B-splines. The coordinate mapping that relates the two images is found using an iterative optimization procedure. This work compares the performance of eight optimization methods: gradient descent (with two different step size selection algorithms), quasi-Newton, nonlinear conjugate gradient, Kiefer-Wolfowitz, simultaneous perturbation, Robbins-Monro, and evolution strategy. Special attention is paid to computation time reduction by using fewer voxels to calculate the cost function and its derivatives. The optimization methods are tested on manually deformed CT images of the heart, on follow-up CT chest scans, and on MR scans of the prostate acquired using a BFFE, Ti, and T2 protocol. Registration accuracy is assessed by computing the overlap of segmented edges. Precision and convergence properties are studied by comparing deformation fields. The results show that the Rob- bins-Monro method is the best choice in most applications. With this approach, the computation time per iteration can be lowered approximately 500 times without affecting the rate of convergence by using a small subset of the image, randomly selected in every iteration, to compute the derivative of the mutual information. From the other methods the quasi-Newton and the nonlinear conjugate gradient method achieve a slightly higher precision, at the price of larger computation times. [ABSTRACT FROM AUTHOR]

Medical images that are to be registered for clinical application often contain both structures that deform and ones that remain rigid. Nonrigid registration algorithms that do not model properties of different tissue types may result in deformations of rigid structures. In this article a local rigidity penalty term is proposed which is included in the registration function in order to penalize the deformation of rigid objects. This term can be used for any representation of the deformation field capable of modelling locally rigid transformations. By using a B-spline representation of the deformation field, a fast algorithm can be devised. The proposed method is compared with an unconstrained nonrigid registration algorithm. It is evaluated on clinical three-dimensional CT follow-up data of the thorax and on two-dimensional DSA image sequences. The results show that nonrigid registration using the proposed rigidity penalty term is capable of nonrigidly aligning images, while keeping user-defined structures locally rigid. [ABSTRACT FROM AUTHOR]

Abstract: Microcrystalline silicon carbide (μc-SiC) was prepared at substrate temperatures between 300 °C and 450 °C using hot-wire chemical vapour deposition (HWCVD). The SiC films were deposited from monomethylsilane (MMS) diluted in hydrogen on glass and crystalline silicon substrates. The influence of the hydrogen dilution, the filament temperature and the deposition pressure on the deposition rate, the structural and the optoelectronic properties was investigated. Infrared and Raman spectroscopy and transmission electron microscopy (TEM) were employed to study the structural properties. Optical absorption measurements by photothermal deflection spectroscopy (PDS) as well as dark- and photo-conductivity measurements were used to investigate the optoelectronic properties of the material. [Copyright &y& Elsevier]

Abstract: Improving the deposition rate for microcrystalline silicon (μc-Si:H) prepared by Hot Wire Chemical Vapour Deposition (HWCVD) under the constraint of a low substrate temperature is the subject of this study. The influence of the deposition pressure and various combinations of filament configuration and filament temperature on the deposition rate and material quality was investigated. Raman and infrared spectroscopy and solar cell J–V parameters are used to evaluate the quality of the material. Low deposition pressures and low filament temperatures at low filament–substrate distances are most suitable to obtain high quality material at improved deposition rates. Deposition rates of 4 Å/s were achieved for high quality material at a substrate temperature of 250 °C. [Copyright &y& Elsevier]

In the early years of e-Commerce, the tourism sector had high expectations for on- line booking. All the major airlines invested huge sums of money, not only to make booking features available, but also to integrate them into attractive, easy-to-use Web offerings. Nevertheless; even after years of investment and improvements, the booking ratio for all but the no-frills airlines is still disappointing. This paper discusses reasons for the slow adoption of online booking. Online booking systems are analyzed as consumer information environments for scheduled airline tickets. The analyses are based on two experiments conducted in 1999 and 2002 respectively. The negative effects of the underlying market structure and the product complexity in the adoption of online booking is also discussed. [ABSTRACT FROM AUTHOR]

Microcrystalline silicon (μc-Si:H) prepared by hot-wire chemical vapour deposition (HWCVD) at low substrate temperature TS and low deposition pressure exhibits excellent material quality and performance in solar cells. Prepared at TS below 250 °C, μc-Si:H has very low spin densities, low optical absorption below the band gap, high photosensitivities, high hydrogen content and a compact structure, as evidenced by the low oxygen content and the weak 2100 cm−1 IR absorption mode. Similar to PECVD material, solar cells prepared with HWCVD i-layers show increasing open circuit voltages Voc with increasing silane concentration. The best performance is achieved near the transition to amorphous growth, and such solar cells exhibit very high Voc up to 600 mV. The structural analysis by Raman spectroscopy, X-ray diffraction (XRD) and transmission electron microscopy (TEM) shows considerable amorphous volume fractions in the cells with high Voc. Raman spectra show a continuously increasing amorphous peak with increasing Voc. Crystalline fractions XC ranging from 50% for the highest Voc to 95% for the lowest Voc were obtained by XRD. XRD-measurements with different incident beam angles, TEM images and electron diffraction patterns indicate a homogeneous distribution of the amorphous material across the i-layer. Nearly no light induced degradation was observed in the cell with the highest XC, but solar cells with high amorphous volume fractions exhibit up to 10% degradation of the cell efficiency. [Copyright &y& Elsevier]

In this study, TaqMan™ PCR was used to assess viral replication of HIV-1 infected cells in vitro. This PCR technique was compared with p24 ELISA as a standard method to monitor HIV-1 replication in cell culture. Hut78 T-lymphoblastoid cells were infected with different titres of HIV-1IIIb (MOI 0.05–0.0005). The course of HIV-1 replication was monitored by determination of p24 concentrations by ELISA in cell culture supernatants and by quantitation of HIV-1 gag RNA by TaqMan™ RT-PCR. Additionally, the number of HIV-1 proviral copies was assessed by TaqMan™ PCR. Monitoring of HIV-1 replication by p24 ELISA and TaqMan™ RT-PCR revealed comparable kinetics of infection. Both methods provided similar data on the exponential increase and on plateauing of HIV-1 replication. Furthermore, both methods were equally sensitive. However, a 7 log linearity of TaqMan™ HIV-1 gag PCR was demonstrated without dilution of the specimen, in contrast to p24 ELISA, where because of its narrow range of detectable p24 concentrations, sample dilution was necessary. Although determination of the number of proviral copies by TaqMan™ PCR does not measure HIV-1 replication, the kinetics of proviral copy number following in vitro inoculation of cells with HIV-1 was nearly the same as the kinetics of HIV-1 RNA copy numbers. In conclusion, TaqMan™ real-time RT-PCR was demonstrated as a reliable and sensitive tool to quantify and monitor HIV-1 replication in cell culture. It is suggested, therefore, that this technique be an alternative method to monitor HIV-1 replication in vitro. [Copyright &y& Elsevier]

Leukaemic patients with advanced disease and severe fungal infections as well as older patients with substantial co-morbidity are usually excluded from conventional allotransplantation because of increased morbidity and mortality. We approached allogeneic transplantation in four patients with a median age of 62 years (one chronic myeloid leukaemia in blast crisis, one high-risk acute myeloid leukaemia (AML) in first complete remission (CR1), one AML in 2nd relapse, one AML in CR2 with pre-existing fungal lung infections (two aspergillus, two mucor) and additional co-morbidity (diabetes n = 2, aortic aneurysm n = 1, arterial sclerosis n = 2) by combining non-myeloablative conditioning with an intensified supportive care regimen, including amphotericin B and 4–12 (median 9) prophylactic granulocyte transfusions from granulocyte colony-stimulating factor (G-CSF)-stimulated volunteer donors. G-CSF was also given to patients until neutrophil recovery. All four patients recovered to a neutrophil count of 0·5 × 109/l after a median of 11·5 d (range 11–13 d). Prophylactic granulocyte transfusions also reduced the need for platelet transfusions and minimized mucositis. All patients were discharged at a median of 25 d (range 18–59 d) and are alive and well after a median follow-up of > 390 d (range 336–417 d) without evidence of leukaemia. Regression of the fungal lesions was documented in three patients, with a slight progression detected by computerized tomography scan of the chest in one patient. We conclude that pulmonary fungal infections are not a contraindication for allogeneic stem cell transplantation, if non-myeloablative conditioning regimens are used in combination with granulocyte transfusions, intravenous amphotericin B and G-CSF. [ABSTRACT FROM AUTHOR]

Aims: We report on investigations exploring the P2X3‐receptor antagonist filapixant's effect on taste perception and cough‐reflex sensitivity and describe its pharmacokinetics, including its CYP3A4‐interaction potential. Methods: In a randomized, placebo‐controlled, double‐blind study, 3 × 12 healthy men (18‐45 years) were assigned (3:1) to filapixant (20, 80 or 250 mg by mouth) or placebo twice daily over 2 weeks. A single dose of midazolam (1 mg), a CYP3A4 substrate, was administered with and without filapixant. Assessments included a taste‐strips test, a taste questionnaire, cough challenge with adenosine triphosphate, adverse event reports and standard safety assessments. Results: Taste disturbances were observed mainly in the 250‐mg group: six of nine participants (67%) in this group reported hypo‐ or dysgeusia in the questionnaire; eight participants (89%) reported taste‐related adverse events. Five participants (56%) had a decrease in overall taste‐strips‐test scores ≥2 points (point estimate −1.1 points, 90% confidence interval [−3.3; 1.1]). Cough counts increased with adenosine triphosphate concentration but without major differences between treatments. Filapixant exposure increased proportionally to dose. Co‐administration of filapixant had no clinically relevant effect on midazolam pharmacokinetics. Area under the concentration‐time curve ratios and 90% confidence intervals were within 80‐125%. No serious or severe adverse events were reported. Conclusions: Overall, filapixant was safe and well tolerated, apart from mild, transient taste disturbances. Such disturbances occurred more frequently than expected based on (in vitro) receptor‐selectivity data, suggesting that other factors than P2X3:P2X2/3 selectivity might also play an important role in this context. The cough‐challenge test showed no clear treatment effect. Filapixant has no clinically relevant CYP3A4 interaction potential. [ABSTRACT FROM AUTHOR]

• Co-init DEBM estimates subtype-specific disease timelines from cross-sectional data. • APOE -specific differences in Alzheimers disease progression have been identified. • Understanding such differences could benefit patient monitoring in the future. Alzheimer's disease (AD) is the most common form of dementia and is phenotypically heterogeneous. APOE is a triallelic gene which correlates with phenotypic heterogeneity in AD. In this work, we determined the effect of APOE alleles on the disease progression timeline of AD using a discriminative event-based model (DEBM). Since DEBM is a data-driven model, stratification into smaller disease subgroups would lead to more inaccurate models as compared to fitting the model on the entire dataset. Hence our secondary aim is to propose and evaluate novel approaches in which we split the different steps of DEBM into group-aspecific and group-specific parts, where the entire dataset is used to train the group-aspecific parts and only the data from a specific group is used to train the group-specific parts of the DEBM. We performed simulation experiments to benchmark the accuracy of the proposed approaches and to select the optimal approach. Subsequently, the chosen approach was applied to the baseline data of 417 cognitively normal, 235 mild cognitively impaired who convert to AD within 3 years, and 342 AD patients from the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset to gain new insights into the effect of APOE carriership on the disease progression timeline of AD. In the ε 4 carrier group, the model predicted with high confidence that CSF Amyloid β 42 and the cognitive score of Alzheimer's Disease Assessment Scale (ADAS) are early biomarkers. Hippocampus was the earliest volumetric biomarker to become abnormal, closely followed by the CSF Phosphorylated Tau 181 (PTAU) biomarker. In the homozygous ε 3 carrier group, the model predicted a similar ordering among CSF biomarkers. However, the volume of the fusiform gyrus was identified as one of the earliest volumetric biomarker. While the findings in the ε 4 carrier and the homozygous ε 3 carrier groups fit the current understanding of progression of AD, the finding in the ε 2 carrier group did not. The model predicted, with relatively low confidence, CSF Neurogranin as one of the earliest biomarkers along with cognitive score of Mini-Mental State Examination (MMSE). Amyloid β 42 was found to become abnormal after PTAU. The presented models could aid understanding of the disease, and in selecting homogeneous group of presymptomatic subjects at-risk of developing symptoms for clinical trials. [ABSTRACT FROM AUTHOR]

The Raman signal can be strongly increased for molecules deposited on a thin metal film in a configuration where the emission of the Raman signal into a glass support of the film is mediated by leaky surface plasmons (SPs). Here we show that SP provides an efficient pathway to detect tip enhanced Raman scattering (TERS). Based on this result, we suggest a new edge plasmon mediated TERS configuration. Plasmon modes on metal covered edges of a dielectric tetrahedral tip couple to a highly directional beam of light into the dielectric body of the tip as a pathway for signal detection. [ABSTRACT FROM AUTHOR]

Abstract: Microcrystalline silicon carbide (μc-SiC) was prepared at low substrate temperatures using Hot Wire chemical vapor deposition (HWCVD). High crystalline volume fractions were achieved at high hydrogen dilution and high deposition pressure. Without intentional doping, such material shows high dark conductivity and high optical absorption below the band gap. The material prepared at low deposition pressure or low hydrogen dilution, on the other hand, shows much lower conductivity and sub-gap absorption, but high spin densities up to 5×1019 cm−3. This high absorption can be attributed to free carriers, different to μc-Si:H where a correlation between the sub-gap absorption and the spin density is observed. [Copyright &y& Elsevier]

Background: Afferent neuronal hypersensitization via P2X3 receptor signaling has been implicated as a driver of several disorders, including refractory chronic cough, endometriosis, diabetic neuropathic pain, and overactive bladder. Eliapixant, a selective P2X3 receptor antagonist, has been in clinical development for all four disorders. Objective: This paper describes pharmacokinetic (PK) and safety data from two phase I studies of eliapixant in healthy Japanese and Chinese participants and compares those data within the two populations and with previous multiple dose data from Caucasian participants. Methods: Two separate phase I, single-center, randomized, placebo-controlled studies were conducted with healthy male participants. The Japanese study was single-blind and the Chinese study was double-blind. Eliapixant was administered as an oral amorphous solid dispersion immediate-release tablet in strengths of 25 mg, 75 mg, and 150 mg. PK characteristics after a single dose (SD) and at steady state (multiple dose [MD], twice daily), adverse events (AEs), and tolerability were evaluated. A post hoc comparison of PK characteristics after SD of eliapixant in Japanese and Chinese participants, and after MD of eliapixant in Japanese, Chinese, and Caucasian participants, was performed. Results: Overall, 36/39 participants enrolled in the Japanese/Chinese studies, respectively (mean [standard deviation] age 25.4 [6.5] and 26.7 [5.0] years, respectively). After SD administration, maximum plasma concentration (Cmax) was higher among Japanese than Chinese participants in the 25 mg and 75 mg dose groups, but comparable in the 150 mg dose group. The area under the concentration–time curve (AUC) was comparable between Japanese and Chinese participants in the 25 mg and 75 mg dose groups, but lower among Japanese participants in the 150 mg group. Half-lives after SD and MD administration were also comparable in Japanese and Chinese participants. The post hoc analysis included 26 Japanese, 30 Chinese, and 50 Caucasian participants. Comparable exposure (Cmax,md and AUC[0–12]md) was observed after MD administration of eliapixant in Chinese and/or Japanese compared with Caucasian participants (geometric mean inter-ethnic ratios close to 1). The trough plasma concentration after eliapixant 150 mg MD, which was assumed to be relevant to eliapixant efficacy, was comparable across all ethnicity groups. Most AEs reported in the Japanese (eliapixant 75 mg SD, n = 2; eliapixant 150 mg MD, n = 2) and Chinese participants (eliapixant 25 mg SD, n = 7; eliapixant 75 mg SD, n = 6; eliapixant 150 mg SD, n = 7; eliapixant 150 mg MD, n = 9; placebo SD, n = 5; placebo MD, n = 1) were of mild intensity. Higher incidences of AEs in the Chinese population were likely due to differing standards of AE reporting between investigators. Conclusion: Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants. Registration: ClinicalTrials.gov identifier numbers: NCT04265781 and NCT04802343. [ABSTRACT FROM AUTHOR]

MICA polymorphisms have been associated with increased incidence of acute GvHD and adverse outcome in allogeneic haematopoietic stem cell transplantation (HSCT). MICB is another expressed member of MHC class I‐related chain genes and its impact on HSCT outcome is yet to be fully defined. We typed a large cohort of patients and donors for MICB polymorphisms and investigated the impact of MICB matching on outcome after unrelated HSCT. 69.2% of the patients were 10/10 human leukocyte antigen (HLA) matched and 30.8% were 9/10 HLA matched. MICB typing was performed using a short amplicon‐based NGS typing assay on the Illumina MiSeq platform. Differences in proteins were considered as mismatches. MICA polymorphisms were identified as possible confounder and were therefore included as parameter in the multivariate analyses. Due to the strong linkage disequilibrium with the classical HLA‐genes, sub‐stratification for HLA matching status was necessary, and no effect of MICB mismatches was seen in the 10/10 HLA matched group when compared to the MICB matched cases. However, in the 9/10 HLA matched group, MICB mismatched cases showed significantly worse disease free survival (DFS), GvHD and relapse free survival (GRFS) compared to the MICB matched cases (DFS: HR 1.24, p = 0.011; GRFS: HR 1.26, p = 0.002). MICA mismatches had no impact on any outcome parameter. According to our findings, effects previously attributed to MICA differences may have been confounded by MICB polymorphisms. We show that MICB differences contribute a small but relevant effect in 9/10 HLA‐matched transplantations, which in turn highlights the possible usefulness of MICB typing in donor selection among similarly suitable 9/10 matched donors, especially when HLA‐B mismatches have to be accepted. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to improve the preoperative classification of nerve sheath tumors using radiomics, a method that extracts quantitative data from medical images. By analyzing MRI scans, we seek to develop a more accurate way to distinguish between different types of nerve sheath tumors before surgery. Our findings could lead to better treatment planning and outcomes for patients with these tumors. This research has the potential to enhance the diagnostic process and contribute to more personalized care for individuals with nerve sheath tumors, ultimately benefiting the medical community and patients alike. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors prevalent in neurofibromatosis type 1 (NF1) patients, posing a significant risk of metastasis and recurrence. Current magnetic resonance imaging (MRI) imaging lacks decisiveness in distinguishing benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs, necessitating invasive biopsies. This study aims to develop a radiomics model using quantitative imaging features and machine learning to distinguish MPNSTs from BPNSTs. Clinical data and MRIs from MPNST and BPNST patients (2000–2019) were collected at a tertiary sarcoma referral center. Lesions were manually and semi-automatically segmented on MRI scans, and radiomics features were extracted using the Workflow for Optimal Radiomics Classification (WORC) algorithm, employing automated machine learning. The evaluation was conducted using a 100× random-split cross-validation. A total of 35 MPNSTs and 74 BPNSTs were included. The T1-weighted (T1w) MRI radiomics model outperformed others with an area under the curve (AUC) of 0.71. The incorporation of additional MRI scans did not enhance performance. Combining T1w MRI with clinical features achieved an AUC of 0.74. Experienced radiologists achieved AUCs of 0.75 and 0.66, respectively. Radiomics based on T1w MRI scans and clinical features show some ability to distinguish MPNSTs from BPNSTs, potentially aiding in the management of these tumors. [ABSTRACT FROM AUTHOR]

Trefoil factor family peptide 3 (TFF3) is supposed to have tumor suppressive functions in retinoblastoma (RB), but the functional pathway is not completely understood. In the study presented, we investigated the downstream pathway of TFF3 signaling in Y79 RB cells. Results from pG13-luciferase reporter assays and western blot analyses indicate induced p53 activity with an upregulation of miR-34a after TFF3 overexpression. Expression levels of the predicted miR-34a target epithelial membrane protein 1 (EMP1) are reduced after TFF3 overexpression. As revealed by WST-1 assay, BrdU, and DAPI cell counts viability and proliferation of Y79 cells significantly decrease following EMP1 knockdown, while apoptosis levels significantly increase. Opposite effects on Y79 cells' growth could be shown after EMP1 overexpression. Caspase assays showed that EMP1 induced apoptosis after overexpression is at least partially caspase-3/7 dependent. Colony formation and soft agarose assays, testing for anchorage independent growth, revealed that EMP1 overexpressing Y79 cells have a significantly higher ability to form colonies. In in ovo chicken chorioallantoic membrane (CAM) assays inoculated EMP1 overexpressing Y79 cells form significantly larger CAM tumors. Moreover, miR-34a overexpression increases sensitivity of Y79 cells towards RB chemotherapeutics, however, without involvement of EMP1. In summary, the TFF3 signaling pathway in Y79 RB cells involves the activation of p53 with downstream induction of miR-34a and subsequent inhibition of EMP1. [ABSTRACT FROM AUTHOR]

Lower-limb exoskeletons could improve the mobility of people with disabilities, older adults, workers, first responders, and military personnel. Despite recent advances, few products are commercially available and exoskeleton research is still often limited by hardware constraints. Many promising multi-joint assistance strategies, especially those with high-torque and high-power components, have yet to be tested because they are beyond the capabilities of current devices. To study these untested assistance strategies, we present a hip–knee–ankle exoskeleton emulator that can apply high torques and powers that match or exceed those observed in uphill running. The system has powerful off-board motors that actuate a 13.5 kg exoskeleton end effector worn by the user. It can apply up to 200 Nm of torque in hip flexion, hip extension, and ankle plantarflexion, 250 Nm of torque in knee extension, and 140 Nm of torque in knee flexion, with over 4.5 kW of power at each joint and a closed-loop torque bandwidth of at least 18 Hz in each direction of actuation. The exoskeleton is compliant in unactuated directions, adjustable for a wide range of users and comfortable during walking and running. When paired with human-in-the-loop optimization, we expect that this system will identify new assistance strategies to improve human mobility. A complete computer-aided design (CAD) model of the exoskeleton and a bill of materials are included and available for download. [ABSTRACT FROM AUTHOR]

Background: Obesity, specifically abdominal adiposity, is associated with increased risks of lung function impairment and asthma in children, but potential adverse effects among adolescents are unknown. We hypothesized that elevated amounts of specific abdominal fat depots during childhood and adolescence may lead to adverse respiratory outcomes in adolescents. Methods: In a population‐based prospective cohort study among 2877 children at 13 years, we measured specific abdominal fat depots including subcutaneous fat mass and visceral fat mass by magnetic resonance imaging. Lung function was measured by spirometry, and current asthma by a questionnaire. Conditional regression analyses were used to examine the associations of abdominal fat depots with respiratory outcomes in adolescence. Results: After adjustment for confounders and child's body mass index, higher subcutaneous and visceral fat mass index at age 13 years, independent of these measures at earlier age, were associated with lower FEV1, FEV1/FVC, and FEF75 (range Z‐score difference (95% CI): −0.10 (−0.15, −0.06) to −0.06 (−0.11, −0.01)). Also, an increase in subcutaneous and visceral fat between ages 10 and 13 years was associated with a decrease in FEV1, FEV1/FVC, and FEF75 during the same period. No associations of abdominal fat depots with asthma were observed. Conclusion: Adolescents with higher amounts of subcutaneous and visceral fat, independent of that at an earlier age and body mass index, have an increased risk of lung function impairment. [ABSTRACT FROM AUTHOR]

Purpose: Support groups might help survivors of allogeneic hematopoietic cell transplantations (HCT) to cope with medical, psychological, and social challenges. The aim of this project was (1) to establish a facilitated post-HCT support group and (2) to assess the participation behaviour. Methods: From 11/2013 until 7/2017, all adult patients who had received a HCT at our centre were invited to participate in a professionally facilitated support group. The format of the group was unstructured without any rules regarding regular attendance. The attendance was prospectively minuted by the facilitator. Reasons for non-attendance were assessed by a survey. Results: During the observation period, 53 group meetings were scheduled. Nine meetings were cancelled because of low attendance. Altogether 23 different patients (F: n=10; M: n=13) and 10 spouses (F: n=9; M: n=1) participated. Median participation was 5 [range 2–11]. With respect to all HCT patients who had the theoretical opportunity to attend, the mean participation rate was 7%. Thirteen patients and four spouses attended more than one meeting. The median count of participations among those participants was 8 [2-32]. The median interval from the first until the last participation was 16 months. The main reason reported for non-participation was the effort to get to the venue of the support group. Conclusions: To our knowledge, this is the first analysis on the attendance behaviour of the participants of a support group for HCT survivors. The results provide guidance for the organization of future support groups and indicate what participation rates can be expected and how they might be increased. [ABSTRACT FROM AUTHOR]

Musculoskeletal imaging is mainly based on the subjective and qualitative analysis of imaging examinations. However, integration of quantitative assessment of imaging data could increase the value of imaging in both research and clinical practice. Some imaging modalities, such as perfusion magnetic resonance imaging (MRI), diffusion MRI, or T2 mapping, are intrinsically quantitative. But conventional morphological imaging can also be analyzed through the quantification of various parameters. The quantitative data retrieved from imaging examinations can serve as biomarkers and be used to support diagnosis, determine patient prognosis, or monitor therapy.We focus on the value, or clinical utility, of quantitative imaging in the musculoskeletal field. There is currently a trend to move from volume- to value-based payments. This review contains definitions and examines the role that quantitative imaging may play in the implementation of value-based health care. The influence of artificial intelligence on the value of quantitative musculoskeletal imaging is also discussed. [ABSTRACT FROM AUTHOR]

Summary: Background: Body composition between prepubertal children and adolescents varies, and it is unclear how physical activity and sedentary behaviour affect adolescent body composition. Objectives: This study aimed to examine the associations of physical activity and screen time with overall and specific fat depots in the general adolescent population. Methods: In a population‐based prospective cohort study, among 3258 adolescents aged 13 years, physical activity and screen time were assessed via self‐report questionnaires. Body mass index, dual‐energy X‐ray absorptiometry‐based measures (i.e. fat mass and lean body mass) and magnetic resonance imaging–based measures (i.e. abdominal subcutaneous and visceral fat mass) were obtained. Results: After adjusting for social‐demographic and growth‐related factors, each additional hour of daily physical activity was associated with lower fat mass, abdominal visceral fat mass and higher lean body mass (all p < 0.05). However, these associations were not observed in the longitudinal analyses. Each additional hour of daily screen time was associated with higher body mass index, fat mass, abdominal subcutaneous and visceral fat mass (all p < 0.05), which were consistent with the longitudinal analyses. Conclusion: Adolescents with higher physical activity and lower screen time had lower levels of adiposity both at the general and visceral levels. [ABSTRACT FROM AUTHOR]