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Background No treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.Methods Adult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.Results Between June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.Conclusion The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

In 2013, the European Commission founded the platform European Innovation Partnership on Active and Healthy Aging as a communication and innovation network in this domain. The goal of the current study was the development of an integrated regional ecosystem for active and healthy aging for the region of Styria via a step-by-step co-creation process. A mixed model approach was used to establish an ecosystem for active and healthy aging, which includes macro-, meso- and micro-level stakeholders in the province of Styria, Austria. Based on the results, eight recommendations for the deployment of a healthy aging region were developed. The visibility and accessibility of healthy aging products and services were evaluated as key factors for innovation in active and healthy aging in the region. Health professionals were identified as major drivers of innovation related to active and healthy aging in Styria. The study presented in this article assessed the capacities for healthy aging in the Styria region and identified the need to improve communication pathways between all levels of the public health system and market.

Lumbar spine disorders (LSD) might influence the outcome after total hip arthroplasty (THA). Despite a known common prevalence of LSD and degenerative hip disorders, this study investigates their mutual influence in case of co-existence with the purpose to advance surgeons planning and patient’s prognosis. Patients with and without LSD were compared before and at the one-year postoperative examination. For clinical evaluation the WOMAC was assessed. The radiological analysis focused on cup anteversion and inclination. The total group included 203 consecutive patients. The overall incidence of LSD was 51.0%. Patients with LSD were on average 4.3 years older and had a 1.8 higher BMI than non-LSD patients (P0.05). No hip dislocations nor clinical signs of impingement were seen.We can conclude that there is a high degree of co-existence of LSD and hip disorders. However, a strong negative impact of LSD to clinical or radiologic results could not be confirmed in our study.

Programmed cell death (PCD) is a genetically controlled pathway that plants can use to selectively eliminate redundant or damaged cells. In addition to its fundamental role in plant development, PCD can often be activated as an essential defense response when dealing with biotic and abiotic stresses. For example, localized, tightly controlled PCD can promote plant survival by restricting pathogen growth, driving the development of morphological traits for stress tolerance such as aerenchyma, or triggering systemic pro-survival responses. Relatively little is known about the molecular control of this essential process in plants, especially in comparison to well-described cell death models in animals. However, the networks orchestrating transcriptional regulation of plant PCD are emerging. Transcription factors (TFs) regulate the clusters of stimuli inducible genes and play a fundamental role in plant responses, such as PCD, to abiotic and biotic stresses. Here, we discuss the roles of different classes of transcription factors, including members of NAC, ERF and WRKY families, in cell fate regulation in response to environmental stresses. The role of TFs in stress-induced mitochondrial retrograde signaling is also reviewed in the context of life-and-death decisions of the plant cell and future research directions for further elucidation of TF-mediated control of stress-induced PCD events are proposed. An increased understanding of these complex signaling networks will inform and facilitate future breeding strategies to increase crop tolerance to disease and/or abiotic stresses.

The article describes the adaption and properties of a model concrete for detailed flow studies. To adapt the yield stress and plastic viscosity of the model concrete to the corresponding rheological properties of real concrete, the model concrete is made of a mixture of glass beads and a non-Newtonian fluid. The refractive index of the non-Newtonian fluid is adjusted to the refractive index of the glass beads by the addition of a further constituent. The rheological properties of the model concrete are characterised by measurements in concrete rheometers. Finally, the first exemplary results from experiments with the model concrete are presented, which give incipient impressions of the complex internal dynamics in flowing concrete.

Introduction: Current atrial fibrillation (AF) guidelines recommend flecainide as a first-line rhythm control option in patients without structural heart disease. While there is proven efficacy in clinical trials and guideline support, it is hypothesized that flecainide may be underutilized due to negative outcomes in the CAST trial and that adverse effects are less common than previously perceived. Methods: This retrospective chart review evaluated patients ⩾18 years initiated on flecainide for AF from August 2011 to October 2016 by a cardiology provider at the study site. Exclusion criteria included:

Objective Hepatocellular carcinoma (HCC) is the most common cause of primary liver cancer. A major part of diagnostic HCC work-up is based on imaging findings from sonography, computed tomography (CT), or magnetic resonance imaging (MRI) scans. Contrast-enhanced ultrasound (CEUS) allows for the dynamic assessment of the microperfusion pattern of suspicious liver lesions. This study aimed to evaluate the diagnostic value of CEUS compared with CT scans for assessing HCC. Methods We performed a retrospective, single-center study between 2004 and 2018 on 234 patients with suspicious liver lesions who underwent CEUS and CT examinations. All patients underwent native B-mode, color Doppler and CEUS after providing informed consent. Every CEUS examination was performed and interpreted by a single experienced radiologist (European Federation of Societies for Ultrasound in Medicine and Biology level 3). Results CEUS was performed on all included patients without occurrence of any adverse effects. CEUS showed a sensitivity of 94%, a specificity of 70%, a positive predictive value of 93% and a negative predictive value of 72% for analyzing HCC compared with CT as the diagnostic gold standard. Conclusions CEUS has an excellent safety profile and shows a high diagnostic accuracy in assessing HCC compared with corresponding results from CT scans.

IntroductionPreterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data.Methods and analysisTheirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at

As part of a Germany-wide project that evaluates strategies for the reduction of multi-resistant bacteria along the poultry production chain, the impact of different hatching egg disinfectants on hatchability and health of the broiler chicks was evaluated. Animal trials were conducted with extended-spectrum beta-lactamase- (ESBL) producing Escherichia (E.) coli contaminated hatching eggs and six disinfection protocols that used formaldehyde, hydrogen peroxide, low-energy electron irradiation, peracetic acid and an essential oil preparation. Each protocol was tested on a group of 50 chicks. Equally sized positive and negative control groups were carried along for each trial. Hatchability, mortality and body weight were recorded as performance parameters. During necropsy of half of the animals in each group on day 7 and 14 respectively, macroscopic abnormalities, body weight, weights of liver and gut convolute were recorded and a range of tissue samples for histological examination were collected as part of the health assessment. A decrease in hatchability was recorded for spray application of essential oils. Body weight development was overall comparable, in several groups even superior, to the Ross308 performance objectives, but a reduced performance was seen in the hydrogen peroxide group. Histologically, lymphoid follicles were regularly seen in all sampled organs and no consistent differences were observed between contaminated and non-contaminated groups. Significances were infrequently and inconsistently seen. In conclusion, remarkable findings were a decrease in hatchability caused by the essential oils spray application and a reduced body weight development in the hydrogen peroxide group. Therefore, the essential oils preparation as spray application was deemed inappropriate in practice, while the application of hydrogen peroxide was considered in need of further research. The other trial results indicate that the tested hatching egg disinfectants present a possible alternative to formaldehyde.

BackgroundModular stems are widely used in revision total hip arthroplasty (THA) with aseptic loosening being a common reason for revision. Despite the good results reported on the use of modular stem designs, there are only few studies focusing on aseptic revisions and few studies on a hexagonal stem design. The goal of this study is to determine stem survival, clinical and functional outcome along with possible risk factors for implant failure in aseptic revision THA.MethodsWe retrospectively identified 53 patients with aseptic THA revision using a modular hexagonal stem with a minimum follow-up of two years. Femoral bone loss, radiographic and clinical outcomes as well as function measured using the Harris Hip Score (HHS) was assessed. Patients' previous medical history was analyzed for comorbidities and the body mass index. Stem survival was calculated using the Kaplan-Meier method. Possible risk factors for implant failure were analyzed using the log-rank test. The median age at revision was 69 (IQR 62-73) with a median follow up of 74 months.ResultsImplant survival rates amounted to 90.4% at 3 and 5 years. The median HHS improved by 47 points (34 (IQR 22-47) vs 81 (IQR 59-90) pConclusionA modular, hexagonal stem can be successfully used in aseptic revision THA with remarkable functional results and excellent survivorship. Revision of a cemented stem using this implant might result in reduced survival which must be considered when planning treatment.

The culture of differentiated human airway epithelial cells allows the study of pathogen-host interactions and innate immune responses in a physiologically relevant in vitro model. As the use of primary cell culture has gained popularity the availability of the reagents needed to generate these cultures has increased. In this study we assessed two different media, Promocell and PneumaCult, during the differentiation and maintenance of well-differentiated primary nasal epithelial cell cultures (WD-PNECs). We compared and contrasted the consequences of these media on WD-PNEC morphological and physiological characteristics and their responses to respiratory syncytial virus (RSV) infection. We found that cultures generated using PneumaCult resulted in greater total numbers of smaller, tightly packed, pseudostratified cells. However, cultures from both media resulted in similar proportions of ciliated and goblet cells. There were no differences in RSV growth kinetics, although more ciliated cells were infected in the PneumaCult cultures. There was also significantly more IL-29/IFNλ1 secreted from PneumaCult compared to Promocell cultures following infection. In conclusion, the type of medium used for the differentiation of primary human airway epithelial cells may impact experimental results.

The presence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli on poultry products is an important issue for veterinary and human health due to the zoonotic infection risk for producers and consumers. The present study focuses on testing the efficacy of six different disinfection methods on eggshell samples, aiming to reduce ESBL producing E. coli contamination on the hatching egg. Sterile eggshell cutouts were artificially contaminated with 108 cfu/ml CTX-M-1 producing E. coli and used as a carrier model to analyze the efficacy of six disinfection methods. The contaminated samples were separated into two groups; 1) contaminated and disinfected, 2) contaminated and non-disinfected. Six independent disinfection protocols were performed following product specifications and protocols. Each eggshell sample was separately crushed, and the total viable bacterial count was calculated to determine the disinfection efficacy. Five out of six tested methods (formaldehyde gassing, hydrogen peroxide + alcohol spray, essential oils spray, peracetic acid foam, and low energetic electron radiation) demonstrated a reduction or completely eliminated the initial ESBL producing E. coli contamination. One method (essential oils as cold fog) only partly reached the expected efficacy threshold (reduction of >102 cfu/ml) and the result differed significantly when compared to the reference method i.e. formaldehyde gassing.

Purpose. To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). Methods. Melanoma survivors were identified within two study populations (N=104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. Results. Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N=8), existential problems (N=2), survivor guilt (N=2), and posttraumatic stress disorder (N=6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N=8), hepatitis (N=1), colitis (N=3), and sarcoidosis (N=1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. Conclusion. A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920.

The aim of this work is to improve the particle detection in the phase field of volume of fluid (VOF) simulations included in OpenFOAM. The reliable evaluation of the particle properties is a prerequisite for coupling the VOF method for the primary breakup with an Eulerian–Lagrangian simulation of the secondary breakup. Relevant changes to the code in order to achieve correct detection results are presented. As four numerical test cases demonstrate, the modified algorithm is capable of detecting particles and their size, position and velocity at an evaluation layer accurately.

Within this paper we present Part2Track, a MATLAB software package for the evaluation of 2D Particle Tracking Velocimetry (PTV) measurements. Part2Track is not only capable of handling time resolved image series but also double frame image sets, which are commonly recorded by standard PIV systems. The following work covers a short description of the package’s functionalities and a performance analysis on synthetic images. In order to demonstrate the capabilities of handling realistic, experimental data, two test cases are provided.

Simulations of spray breakup are challenging due to a wide range of different length and time scales. While Volume-of-Fluid (VoF) is suited for the primary breakup, the secondary breakup and the dilute spray cloud is better resolved using a Lagrangian particle tracking (LPT) method. This publication proposes a 3D coupling between both models using the CFD software OpenFOAM to resolve the complete process of spray atomization. Combined with adaptive mesh refinement, the computational cost can be reduced significantly. The simulation of a fuel jet in crossflow demonstrates the accuracy and speedup of the proposed method.

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population, affecting over 55 million people worldwide. Histopathological hallmarks of this multifactorial disease are an increased plaque burden and tangles in the brains of affected individuals. Several lines of evidence indicate that B12 hypovitaminosis is linked to AD. In this review, the biochemical pathways involved in AD that are affected by vitamin B12, focusing on APP processing, Aβ fibrillization, Aβ-induced oxidative damage as well as tau hyperphosphorylation and tau aggregation, are summarized. Besides the mechanistic link, an overview of clinical studies utilizing vitamin B supplementation are given, and a potential link between diseases and medication resulting in a reduced vitamin B12 level and AD are discussed. Besides the disease-mediated B12 hypovitaminosis, the reduction in vitamin B12 levels caused by an increasing change in dietary preferences has been gaining in relevance. In particular, vegetarian and vegan diets are associated with vitamin B12 deficiency, and therefore might have potential implications for AD. In conclusion, our review emphasizes the important role of vitamin B12 in AD, which is particularly important, as even in industrialized countries a large proportion of the population might not be sufficiently supplied with vitamin B12.

The authors wish to make the following corrections to their paper [...]

Reducing disaster risks and adapting to climate change are ever more important policy goals in Europe and worldwide. The commitment to the 2030 Agenda for Sustainable Development and complementary multilateral frameworks, including the Sendai Framework for Disaster Risk Reduction 2015–2030 and the Paris Agreement on Climate Change, has galvanized pursuits for policy coherence. The report Climate change adaptation and disaster risk reduction in Europe: enhancing coherence of the knowledge base, policies and practices of the European Environment Agency identified several ways for how coherence and resilience can be built through knowledge sharing, collaboration and investments.

The wood degrading fungus Schizophyllum commune is a model system for mushroom development. Here, we describe the 38.5 Mb assembled genome of this basidiomycete and application of whole genome expression analysis to study the 13,210 predicted genes. Comparative analyses of the S. commune genome revealed unique wood degrading machinery and mating type loci with the highest number of reported genes. Gene expression analyses revealed that one third of the 471 identified transcription factor genes were differentially expressed during sexual development. Two of these transcription factor genes were deleted. Inactivation of fst4 resulted in the inability to form mushrooms, whereas inactivation of fst3 resulted in more but smaller mushrooms than wild-type. These data illustrate that mechanisms underlying mushroom formation can be dissected using S. commune as a model. This will impact commercial production of mushrooms and the industrial use of these fruiting bodies to produce enzymes and pharmaceuticals

Abstract Background Exposure to traffic-derived particulate matter (PM), such as diesel exhaust particles (DEP), is a leading environmental cause of cardiovascular disease (CVD), and may contribute to endothelial dysfunction and development of atherosclerosis. It is still debated how DEP and other inhaled PM can contribute to CVD. However, organic chemicals (OC) adhered to the particle surface, are considered central to many of the biological effects. In the present study, we have explored the ability of OC from DEP to reach the endothelium and trigger pro-inflammatory reactions, a central step on the path to atherosclerosis. Results Exposure-relevant concentrations of DEP (0.12 μg/cm2) applied on the epithelial side of an alveolar 3D tri-culture, rapidly induced pro-inflammatory and aryl hydrocarbon receptor (AhR)-regulated genes in the basolateral endothelial cells. These effects seem to be due to soluble lipophilic constituents rather than particle translocation. Extractable organic material of DEP (DEP-EOM) was next fractionated with increasing polarity, chemically characterized, and examined for direct effects on pro-inflammatory and AhR-regulated genes in human microvascular endothelial (HMEC-1) cells and primary human endothelial cells (PHEC) from four healthy donors. Exposure-relevant concentrations of lipophilic DEP-EOM (0.15 μg/cm2) induced low to moderate increases in IL-1α, IL-1β, COX2 and MMP-1 gene expression, and the MMP-1 secretion was increased. By contrast, the more polar EOM had negligible effects, even at higher concentrations. Use of pharmacological inhibitors indicated that AhR and protease-activated receptor-2 (PAR-2) were central in regulation of EOM-induced gene expression. Some effects also seemed to be attributed to redox-responses, at least at the highest exposure concentrations tested. Although the most lipophilic EOM, that contained the majority of PAHs and aliphatics, had the clearest low-concentration effects, there was no straight-forward link between chemical composition and biological effects. Conclusion Lipophilic and semi-lipophilic chemicals seemed to detach from DEP, translocate through alveolar epithelial cells and trigger pro-inflammatory reactions in endothelial cells at exposure-relevant concentrations. These effects appeared to be triggered by AhR agonists, and involve PAR-2 signaling.

Molecular doping is routinely used in organic semiconductor devices nowadays, but the physics at play remains unclarified. Tietze et al. describe it as a two-step process and show it costs little, energetically, to dissociate charge transfer complexes due to energetic disorder of organic semiconductors.

Abstract Background The present study contrasts the accuracy of different reconstructed models with distinctive segmentation methods performed by various experts. Seven research groups reconstructed nine 3D models of one human femur based on an acquired CT image using their own computational methods. As a reference model for accuracy assessment, a 3D surface scan of the human femur was created using an optical measuring system. Prior to comparison, the femur was divided into four areas; “neck and greater trochanter”, “proximal metaphysis”, “diaphysis”, and “distal metaphysis”. The deviation analysis was carried out in GEOMAGIC studio v.2013 software. Results The results revealed that the highest deviation errors occurred in “neck and greater trochanter” area and “proximal metaphysis” area with RMSE of 0.84 and 0.83 mm respectively. Conclusion In conclusion, this study shows that the average deviation of reconstructed models prepared by experts with various methods, skills and software from the surface 3D scan is lower than 0.79 mm, which is not a significant discrepancy.

Abstract The WHO has ranked environmental hazardous exposures in the living and working environment among the top risk factors for chronic disease mortality. Worldwide, about 40 million people die each year from noncommunicable diseases (NCDs) including cancer, diabetes, and chronic cardiovascular, neurological and lung diseases. The exposure to ambient pollution in the living and working environment is exacerbated by individual susceptibilities and lifestyle-driven factors to produce complex and complicated NCD etiologies. Research addressing the links between environmental exposure and disease prevalence is key for prevention of the pandemic increase in NCD morbidity and mortality. However, the long latency, the chronic course of some diseases and the necessity to address cumulative exposures over very long periods does mean that it is often difficult to identify causal environmental exposures. EU-funded COST Action DiMoPEx is developing new concepts for a better understanding of health-environment (including gene-environment) interactions in the etiology of NCDs. The overarching idea is to teach and train scientists and physicians to learn how to include efficient and valid exposure assessments in their research and in their clinical practice in current and future cooperative projects. DiMoPEx partners have identified some of the emerging research needs, which include the lack of evidence-based exposure data and the need for human-equivalent animal models mirroring human lifespan and low-dose cumulative exposures. Utilizing an interdisciplinary approach incorporating seven working groups, DiMoPEx will focus on aspects of air pollution with particulate matter including dust and fibers and on exposure to low doses of solvents and sensitizing agents. Biomarkers of early exposure and their associated effects as indicators of disease-derived information will be tested and standardized within individual projects. Risks arising from some NCDs, like pneumoconioses, cancers and allergies, are predictable and preventable. Consequently, preventative action could lead to decreasing disease morbidity and mortality for many of the NCDs that are of major public concern. DiMoPEx plans to catalyze and stimulate interaction of scientists with policy-makers in attacking these exposure-related diseases.

The synthesis, structure, and photocatalytic water splitting performance of two new titania (TiO2)/gold(Au)/Bombyx mori silk hybrid materials are reported. All materials are monoliths with diameters of up to ca. 4.5 cm. The materials are macroscopically homogeneous and porous with surface areas between 170 and 210 m2/g. The diameter of the TiO2 nanoparticles (NPs) – mainly anatase with a minor fraction of brookite – and the Au NPs are on the order of 5 and 7–18 nm, respectively. Addition of poly(ethylene oxide) to the reaction mixture enables pore size tuning, thus providing access to different materials with different photocatalytic activities. Water splitting experiments using a sunlight simulator and a Xe lamp show that the new hybrid materials are effective water splitting catalysts and produce up to 30 mmol of hydrogen per 24 h. Overall the article demonstrates that the combination of a renewable and robust scaffold such as B. mori silk with a photoactive material provides a promising approach to new monolithic photocatalysts that can easily be recycled and show great potential for application in lightweight devices for green fuel production.

Dynamic analyses of vertical hydro power plant rotors require the consideration of the non-linear bearing characteristics. This study investigates the vibrational behavior of a typical vertical machine using a time integration method that considers non-linear bearing forces. Thereby, the influence of support stiffness and unbalance magnitude is examined. The results show a rising influence of unbalance on resonance speed with increasing support stiffness. Furthermore, simulations reveal that the shaft orbit in the bearing is nearly circular for typical design constellations. This property is applied to derive a novel approximation procedure enabling the examination of non-linear resonance behavior, using linear rotor dynamic theory. The procedure considers the dynamic film pressure for determining the pad position. In addition, it is time-efficient compared to a time integration method, especially at high amplitudes when damping becomes small.

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a clinically and genetically heterogeneous disorder primarily characterized by susceptibility to fracture. Although OI generally results from mutations in the type I collagen genes, COL1A1 and COL1A2, the relationship between genotype and phenotype is not yet well understood. To provide additional data for genotype-phenotype analyses and to determine the proportion of mutations in the type I collagen genes among subjects with lethal forms of OI, we sequenced the coding and exon-flanking regions of COL1A1 and COL1A2 in a cohort of 63 subjects with OI type II, the perinatal lethal form of the disease. We identified 61 distinct heterozygous mutations in type I collagen, including five non-synonymous rare variants of unknown significance, of which 43 had not been seen previously. In addition, we found 60 SNPs in COL1A1, of which 17 were not reported previously, and 82 in COL1A2, of which 18 are novel. In three samples without collagen mutations, we found inactivating mutations in CRTAP and LEPRE1, suggesting a frequency of these recessive mutations of approximately 5% in OI type II. A computational model that predicts the outcome of substitutions for glycine within the triple helical domain of collagen alpha1(I) chains predicted lethality with approximately 90% accuracy. The results contribute to the understanding of the etiology of OI by providing data to evaluate and refine current models relating genotype to phenotype and by providing an unbiased indication of the relative frequency of mutations in OI-associated genes.

A new composite photocatalyst called POF/TiO2 was prepared from commercial P25 TiO2 and Posidonia oceanica fibers (POF), a biomaterial collected from Tunisia’s beach. The composite material was prepared by a classical sol-gel synthesis and was characterized by different methods. SEM images show a TiO2 layer formed on top of the fibers, which was verified by XRD and XPS. Diffuse reflectance UV-vis spectroscopy shows that the layer has the same optical properties (Eg = 3.0 eV) as bulk P25. The photodegradation of phenol as a model compound was studied under different operating conditions using POF/TiO2 and the results show degradation efficiencies between 4% (100 ppm) and 100% (2 concentration of about 1 g/L. The composite material showed good stability and could be recycled up to three times.

(1) Background: Chest radiography (CXR) is still a key diagnostic component in the emergency department (ED). Correct interpretation is essential since some pathologies require urgent treatment. This study quantifies potential discrepancies in CXR analysis between radiologists and non-radiology physicians in training with ED experience. (2) Methods: Nine differently qualified physicians (three board-certified radiologists [BCR], three radiology residents [RR], and three non-radiology residents involved in ED [NRR]) evaluated a series of 563 posterior-anterior CXR images by quantifying suspicion for four relevant pathologies: pleural effusion, pneumothorax, pneumonia, and pulmonary nodules. Reading results were noted separately for each hemithorax on a Likert scale (0–4; 0: no suspicion of pathology, 4: safe existence of pathology) adding up to a total of 40,536 reported pathology suspicions. Interrater reliability/correlation and Kruskal–Wallis tests were performed for statistical analysis. (3) Results: While interrater reliability was good among radiologists, major discrepancies between radiologists’ and non-radiologists’ reading results could be observed in all pathologies. Highest overall interrater agreement was found for pneumothorax detection and lowest agreement in raising suspicion for malignancy suspicious nodules. Pleural effusion and pneumonia were often suspected with indifferent choices (1–3). In terms of pneumothorax detection, all readers mainly decided for a clear option (0 or 4). Interrater reliability was usually higher when evaluating the right hemithorax (all pathologies except pneumothorax). (4) Conclusions: Quantified CXR interrater reliability analysis displays a general uncertainty and strongly depends on medical training. NRR can benefit from radiology reporting in terms of time efficiency and diagnostic accuracy. CXR evaluation of long-time trained ED specialists has not been tested.

Background: The aim of this paper was to assess and compare the accuracy of common magnetic resonance imaging (MRI) pulse sequences in measuring the lesion sizes of hepatocellular carcinomas (HCCs) with respect to the Milan criteria and histopathology as a standard of reference. Methods: We included 45 patients with known HCC who underwent contrast-enhanced MRI of the liver prior to liver transplantation or tumor resection. Tumor size was assessed pathologically for all patients. The MRI protocol contained axial T2-weighted images as well as T1-weighted imaging sequences before and after application of Gd-EOB-DTPA. Tumor diameters, the sharpness of lesions, and the presence of artifacts were evaluated visually on all available MRI sequences. MRI measurements and pathologically assessed tumor dimensions were correlated using Pearson’s correlation coefficient and Bland–Altman plots. The rate of misclassifications following Milan criteria was assessed. Results: The mean absolute error (in cm) of MRI size measurements in comparison to pathology was the smallest for the hepatobiliary phase T1-weighted acquisition (0.71 ± 0.70 cm, r = 0.96) and largest for the T2w turbo-spin-echo (TSE) sequence (0.85 ± 0.78 cm, r = 0.94). The misclassification rate regarding tumor size under the Milan criteria was lowest for the T2w half-Fourier acquisition single-shot turbo spin-echo sequence and the hepatobiliary phase T1w acquisition (each 8.6%). The highest rate of misclassification occurred in the portal venous phase T1w acquisition and T2w TSE sequence (each 14.3%). Conclusions: The hepatobiliary phase T1-weighted acquisition seems to be most accurate among commonly used MRI sequences for measuring HCC tumor size, resulting in low rates of misclassification with respect to the Milan criteria.

The application of sliding planet gear bearings in wind turbine gearboxes has become more common in recent years. Assuming practically applied helix angles, the gear mesh of the planet stage causes high force and moment loads for these bearings involving high local loads at the bearing edges. Specific operating behavior and suitable design measures to cope with these challenging conditions are studied in detail based on a thermo-hydrodynamic (THD) bearing model. Radial clearance and axial crowning are identified as important design parameters to reduce maximum pressures occurring at the bearing edges. Furthermore, results indicate that a distinct analysis of the gear mesh load distribution is required to characterize bearing operating behavior at part-load. Here, operating conditions as critical as the ones reached at nominal load might occur. Wear phenomena can improve the shape of the gap in the circumferential as well as in axial direction incorporating a significant reduction of local maximum pressures. The complexity of the combination of these aspects and the additionally expected impact of structure deformation gives an insight into the challenges in the design processes of sliding planet gear bearings for wind turbine gearbox applications.

The use of planetary gear stages intends to increase power density in drive trains of rotating machinery. Due to lightweight requirements on this type of machine elements, structures are comparably flexible while mechanical loads are high. This study investigates the impact of structure deformation on sliding planet gear bearings applied in the planetary stages of wind turbine gearboxes with helical gears. It focuses on three main objectives: (i) development of a procedure for the time-efficient thermo-elasto-hydrodynamic (TEHD) analysis of sliding planet gear bearing; (ii) understanding of the specific deformation characteristics of this application; (iii) investigation of the planet gear bearing’s modified operating behavior, caused by the deformation of the sliding surfaces. Generally, results indicate an improvement of predicted operating conditions by consideration of structure deformation in the bearing analysis for this application. Peak load in the bearing decreases because the loaded proportion of the sliding surface increases. Moreover, tendencies of single design measures, determined for rigid geometries, keep valid but exhibit significantly different magnitudes under consideration of structure deformation. Results show that consideration of structure flexibility is essential for sliding planet gear bearing analysis if quantitative assertions on load distributions, wear phenomena, and interaction of the bearing with other components are required.

Background: In patients with liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) displays an effective method for treating portal hypertension. Main indications include refractory ascites and secondary prevention of esophageal bleeding. Color Doppler ultrasound (CDUS) plays a leading role in the follow-up management, whereas contrast-enhanced ultrasound (CEUS) is not routinely considered. We compared the efficacy of CEUS to CDUS and highlighted differences compared to findings of corresponding computed tomography (CT) and magnetic resonance imaging (MRI). (2) Methods: On a retrospective basis, 106 patients with CEUS examination after TIPS were included. The enrollment period was 12 years (between 2008 and 2020) and the age group ranged from 23.3 to 82.1 years. In addition, 92 CDUS, 43 CT and 58 MRI scans were evaluated for intermodal comparison. (3) Results: Intermodal analysis and comparison revealed a high level of concordance between CDUS, CT and MRI in the vast majority of cases. In comparison to CDUS, the correlation of the relevant findings was 92.5%, 95.3% for CT and 87.9% for MRI. In some cases, however, additional information was provided by CEUS (4) Conclusions: CEUS depicts a safe and effective imaging modality for follow-up after TIPS. In addition to CDUS, CEUS enables specific assessment of stent pathologies and stent dysfunction due to its capacity to dynamically visualize single microbubbles at high spatial and temporal resolution. Due to the low number of adverse events regarding the application of contrast agents, CEUS can be administered to a very broad patient population, thus avoiding additional radiation exposure compared to CT angiography in cases with divergent findings during follow-up.

Counselor education doctoral students are often required to supervise master-level counselors-in-training as part of their supervision internship. While practical, this arrangement places doctoral students and their supervisees in potentially compromised situations, given their lack of experience in these respective roles. This article offers a toolbox of strategies doctoral student supervisors can use to facilitate their work with counselors-in-training. These strategies address focus areas identified through prior research. Doctoral student supervisors are encouraged to use this toolbox in conjunction with the support and guidance of their faculty supervisor as they navigate clinical supervision. [ABSTRACT FROM AUTHOR]

Resumen El síndrome aórtico agudo incluye un grupo de enfermedades que poseen similitud clínica en su historia natural, siendo la característica más importante su asociación a un alto riesgo vital. Entre estas patologías, el diagnóstico y manejo de la disección aórtica depende del grado de compromiso aórtico según la ubicación de la lesión definida bajo la clasificación de Stanford. Dentro de las manifestaciones clave se considera al dolor torácico como el síntoma cardinal. Sin embargo, existen situaciones que por ambigüedad clínica retrasan el diagnóstico. Se presenta el caso de un paciente que debutó con una disección aórtica Stanford A, con indicación de resolución quirúrgica en fase aguda pero que dado lo inespecífico de su cuadro clínico, no se logró un diagnóstico oportuno. Posterior a reiteradas consultas por cambios en su sintomatología, se determinó el cuadro definitivo a través de estudio imagenológico, evolucionando de forma favorable con terapia ambulatoria.