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This study aimed to investigate the effect of TiC and TiB2 nano-inoculants addition on the microstructure and tribological behavior of PH13-8Mo stainless steel processed through wire arc additive manufacturing (WAAM). The incorporation of TiC/TiB2 inoculants demonstrated notable efficiency in mitigating the anisotropic wear and scratch response and enhancing wear resistance observed in the as-printed state. This improvement was ascribed to the refinement of the grain structure, disruption of the columnar structure, and increased content of the retained austenite. Notably, TiB2 inoculation exhibited superior grain refinement and achieved the highest hardness. However, the TiC-inoculated condition demonstrated the best wear resistance, attributed to its excellent combination of hardness and fracture resistance, and a higher contribution of strain-induced martensite transformation during wear testing. Additionally, the implementation of post-printing solutionizing and aging treatment was found to improve the scratch and wear resistance of the alloy, attributed to the formation of nano-sized β-NiAl precipitates. The main wear mechanism observed involved oxidation wear, adhesive wear, and three-body abrasive wear. The findings of this study highlight the significant potential of incorporating ceramic-based nano-particles for improving the wear resistance of WAAM PH13-8Mo components, particularly in demanding applications like injection molding dies where superior abrasion resistance is paramount.

Wire arc additive manufacturing (WAAM) stands as an efficient and cost-effective method for producing large-scale engineering components while minimizing waste. This study explores the influence of WAAM process parameters on nickel aluminum bronze (NAB) parts, focusing on the wire feed rate (WFR) as a key factor governing heat input and its effects on bead geometry, microstructure, and mechanical properties. The investigation involved depositing a single bead from NAB alloy while varying the WFS within the 2–7 m/min range, resulting in heat inputs ranging from 20.600 to 57.960 kJ/m. The results revealed that increasing heat input up to 34.944 kJ/m led to an augmentation in the bead dimensions and increased hardness due to κ-precipitates formation within the α-Cu matrix. However, with further increments in heat input to 49.088 kJ/m and 57.960 kJ/m, the bead dimensions and hardness exhibited a decline as the uniformity of intermetallic κ distribution lessened. Through optimization of WAAM process parameters, a defect-free single-wall NAB was successfully manufactured with enhanced properties. The tensile strength along the horizontal direction for the single-wall NAB alloy was found to be superior to that of the vertical direction, irrespective of the specimen's extraction regions. Additionally, the bottom specimen exhibited slightly higher tensile strength than the center and upper specimens due to being the initial layers of the wall deposited on the substrate plate, undergoing a faster cooling rate. These findings underscore the potential of WAAM as a robust method for the fabrication of larger NAB components with precision and efficiency.

Introduction: Single-station N2 (ssN2) versus multi-station N2 has been used as a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 NSCLC. We hypothesized that clinical staging would be susceptible to upstaging on pathologic staging and, therefore, challenge this practice. Methods: A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed computed tomography (CT), positron emission tomography (PET), and staging endobronchial ultrasound (EBUS) and had been confirmed clinical stage III-ssN2 at multidisciplinary team discussion and went on to complete surgical resection as the first treatment to provide pathologic staging. The study was completed in two cohorts (A) across a single cancer alliance in England (Greater Manchester) January 1, 2015 to December 31, 2018 and (B) across five United Kingdom centers to validate the findings in part A January 1, 2016 to December 31, 2020. Results: A total of 115 patients met the inclusion criteria across cohort A (56 patients) and cohort B (59 patients) across 15 United Kingdom hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathologic stage III-multi-station N2 was 34% (19 of 56) in cohort A, 32% in cohort B (19 of 59), and 33% across the combined study cohort (38 of 115). Most patients had a single radiologically abnormal lymph node on CT and PET (88%, 105 of 115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13 of 38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15 of 38) rather than false-negative sampling during EBUS (26%, 10 of 38). Conclusions: During multidisciplinary team discussions, clinicians must be aware that one-third of patients with stage III-ssN2 on the basis of CT, PET, and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.

This book review discusses Daniel Conway’s Nietzsche’s “Before Good and Evil”, part of the ongoing Edinburgh Critical Guides to Nietzsche edited by Keith Ansell-Pearson and Daniel Conway. Aspects of Conway’s discussion highlighted in the review include Nietzsche’s relation to Plato, the significance of psychology, and the notion of German identity.

The directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOEs) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. The capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print a solid cube with various X–Y and Z overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on the cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and the parametric models showed statistical significance.

Purpose The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.Participants UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40–69 enrolled in 2006–2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to date UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plans The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022–2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

Botulinum neurotoxins (BoNTs) are extremely potent naturally occurring poisons that act by silencing neurotransmission. Intriguingly, in addition to preventing presynaptic vesicle fusion, BoNT serotype A (BoNT/A) can also promote axonal regeneration in preclinical models. Here we report that the non-toxic C-terminal region of the receptor-binding domain of heavy chain BoNT/A (HCC/A) activates the small GTPase Rac1 and ERK pathway to potentiate axonal outgrowth, dendritic protrusion formation and synaptic vesicle release in hippocampal neurons. These data are consistent with HCC/A exerting neurotrophic properties, at least in part, independent of any BoNT catalytic activity or toxic effect.

Changes in chromatin structure are key determinants of genomic responses. Thus, methods that enable such measurements are instrumental for investigating genome regulation and function. Here, we report further developments and validation of a streamlined method of histone-based fluorescence lifetime imaging microscopy (FLIM) that robustly detects chromatin compaction states in fixed and live cells, in 2D and 3D. We present a quality-controlled and detailed method that is simpler and faster than previous methods, and uses FLIMfit open-source software. We demonstrate the versatility of this chromatin FLIM through its combination with immunofluorescence and implementation in immortalised and primary cells. We applied this method to investigate the regulation of chromatin organisation after genotoxic stress and provide new insights into the role of ATM in controlling chromatin structure independently of DNA damage. Collectively, we present an adaptable chromatin FLIM method for examining chromatin structure and establish its utility in mammalian cells.

PURPOSE:Preliminary assessment of a new prototype ultrasound-based hypersonic vitrector (HV) by qualitatively examining the histopathological changes in the retina and vitreous body after pars plana vitrectomy (PPV) and its ability to fragment vitreous collagen. METHODS:Fourteen porcine cadaveric eyes, 20 eyes in live swine and six human cadaveric eyes underwent PPV using the HV or a pneumatic guillotine vitrector (GV). An additional 4 porcine crystalline lenses were touched with either the HV or GV for 1 minute. Following PPV, human vitreous was removed and processed for electron microscopy (EM). Eyes and lenses were fixed and sectioned for light microscopy (LM). RESULTS:There were no macroscopic retinal or optic nerve defects associated with either HV or GV PPVs. Cadaveric retinal specimens showed separation of the inner limiting membrane (ILM) and vacuolization and fragmentation at the nerve fiber layer (NFL) and the ganglion cell layer (GCL). ILM fragmentation and separation were found after PPV in live swine with both vitrectors. Small disruptions of the posterior capsule or structural lens defects were found after HV touch. The EM analysis revealed more fragmentation of human vitreous collagen fibrils after HV compared to GV PPV. CONCLUSIONS:LM and EM analysis of retina, vitreous, and crystalline lens after PPV showed similar morphological changes using the HV or the GV. Vitreous fragmentation appeared more effective with the HV. Overall this study suggests that the HV may be a promising new technology. More work is needed to quantitatively assess its safety and efficacy.

Cet article prend son point de départ dans un poème de Goethe, « Les poèmes sont des vitraux », où la visite d’une église sert comme paradigme de l’expérience esthétique, pour se demander dans quelle mesure on peut comprendre Le Livre Rouge de C. G. Jung du point de vue d’une « cathédrale » pour « les lieux silencieux de l’esprit » (comme Jung le dit dans une conversation avec Christiana Morgan du 12 juillet 1926). Par ailleurs, la conférence de Jung intitulée « À propos de la compréhension psychologique des processus pathologiques » (1914) offre une clé pour résoudre le problème herméneutique qu’est Le Livre Rouge, parce que Jung y mène une enquête sur les relations entre l’art et la nature, entre l’art et la science et entre l’art et la vie. En fin de compte les considérations de Jung sur son Livre Rouge dans Ma vie : Souvenirs, rêves et pensées (1961) posent la question suivante : qu’est-ce que « la fidélité aux obligations intellectuelles et éthiques »? Si on les considère de manière appropriée, il n’y a pas de contradiction entre l’éthique et l’esthétique, car si le monde est justifié comme un phénomène esthétique, si l’on considère sa vie dans sa dimension symbolique et si l’on comprend sa vie comme une œuvre d’art, alors l’éthique est bel et bien l’esthétique.

An elderly patient, with a history of depression with psychosis, presented with breathlessness, a right exudative pleural effusion and a peripheral eosinophilia. The pleural fluid was eosinophil-rich (10% of leucocytes). Olanzapine therapy had been commenced 12 months previously. There was a family history of TB and the patient was of African origin. A full diagnostic work-up ensued including computed tomography of the thorax and local anaesthetic thoracoscopy. The pleura was unremarkable on CT and displayed bland smooth thickening at visual inspection during thoracoscopy. Pleural biopsies demonstrated chronic inflammation with eosinophils but no evidence of granulomatous inflammation or malignancy. Pleural tissue culture did not yield mycobacteria. A diagnosis of olanzapine-induced eosinophilic pleuritis was suspected and the pleural disease resolved with withdrawal of olanzapine. Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion.