Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

We investigated whether an observed reduction in overall childhood cancer risk (<15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.

A series of organoclays with monolayers, bilayers, pseudotrilayers, paraffin monolayers and paraffin bilayers were prepared from montmorillonite by ion exchange with hexadecyltrimethylammonium bromide (HDTMAB). The HDTMAB concentrations used for preparing the organoclays were 0.5, 0.7, 1.0, 1.5, 2.0 and 2.5 times the montmorillonite cation exchange capacity (CEC). The microstructural parameters, including the BET-N2 surface area, pore volume, pore size, and surfactant loading and distribution, were determined by X-ray diffraction, N2 adsorption-desorption and high-resolution thermogravimetric analysis (HRTG). The BET-N2 surface area decreased from 55 to 1 m2/g and the pore volume decreased from 0.11 to 0.01 cm3/g as surfactant loading was increased from Na-Mt to 2.5CEC-Mt. The average pore diameter increased from 6.8 to 16.3 nm as surfactant loading was increased. After modifying montmorillonite with HDTMAB, two basic organoclay models were proposed on the basis of HRTG results: (1) the surfactant mainly occupied the clay interlayer space (0.5CEC-Mt, 0.7CEC-Mt, 1.0CEC-Mt); and (2) both the clay interlayer space and external surface (1.5CEC-Mt, 2.0CEC-Mt, 2.5CEC-Mt) were modified by surfactant. In model 1, the sorption mechanism of p-nitrophenol to the organoclay at a relatively low concentration involved both surface adsorption and partitioning, whereas, in model 2 it mainly involved only partitioning. This study demonstrates that the distribution of adsorbed surfactant and the arrangement of adsorbed HDTMA+ within the clay interlayer space control the efficiency and mechanism of sorption by the organoclay rather than BET-N2 surface area, pore volume, and pore diameter.

The thermal stability of surfactant-modified clays plays a key role in the synthesis and processing of organoclay-based nanocomposites. Differential thermal analysis (DTA), thermogravimetric measurement and differential scanning calorimetry (DSC) were used in this study to characterize the thermal stability of hexadecyltrimethylammonium bromide-modified montmorillonites prepared at different surfactant concentrations. Analysis by DSC shows that the molecular environment of the surfactant within the montmorillonite galleries is different from that in the bulk state. The endothermic peak at 70–100°C in the DTA curves of the modified montmorillonites is attributed to both the surfactant phase transformation and the loss of free and interlayer water. With an increase of surfactant-packing density, the amount of water residing in the modified montmorillonite decreases gradually, reflecting the improvement of the hydrophobic property for the organoclay. However, the increase in the surfactant packing density within the galleries leads to a decrease in the thermal stability of the organoclays.

With an increase of initial surfactant concentration for the preparation of organoclays, the surfactant- packing density increases gradually to a ‘saturated’ state. It was found that the cationic surfactant was introduced into the montmorillonite interlayer not only by cation exchange but also by physical adsorption.

The ordering conformation of surfactant molecules in intercalated montmorillonite prepared at various concentrations was investigated by 13C MAS NMR. The 13C MAS NMR study demonstrates the coexistence of ordered and disordered chain conformations. Two main resonance peaks are associated with the backbone alkyl chains: the resonance at 33 ppm corresponds to the ordered conformation (all-trans), and the resonance at 30 ppm corresponds to the disordered conformation (mixture of trans and gauche). Deconvolution of 13C MAS NMR spectra indicates that the ordering conformation of surfactant molecules within the gallery of montmorillonite depends very much on their orientation and packing density. When amine chains are oriented parallel to the silicate layers, the amount of all-trans conformer decreases with the increase of amine concentration. However, the amount of all-trans conformer increases with the increase of amine concentration when amine chains radiate from the silicate layers. Furthermore, 13C MAS NMR spectra show that the intercalated surfactant molecules in the clay minerals never attained the complete liquidlike or solidlike behavior.

High-intensity vortex beams with tunable topological charges and low coherence are highly demanded in applications such as inertial confinement fusion (ICF) and optical communication. However, traditional optical vortices featuring nonuniform intensity distributions are dramatically restricted in application scenarios that require a high-intensity vortex beam owing to their ineffective amplification resulting from the intensity-dependent nonlinear effect. Here, a low-coherence perfect vortex beam (PVB) with a topological charge as high as 140 is realized based on the super-pixel wavefront-shaping technique. More importantly, a globally adaptive feedback algorithm (GAFA) is proposed to efficiently suppress the original intensity fluctuation and achieve a flat-top PVB with dramatically reduced beam speckle contrast. The GAFA-based flat-top PVB generation method can pave the way for high-intensity vortex beam generation, which is crucial for potential applications in ICF, laser processing, optical communication and optical trapping.

Sensory differences and anxiety disorders are highly prevalent in autistic individuals with and without ADHD. Studies have shown that sensory differences and anxiety are associated and that intolerance of uncertainty (IU) plays an important role in this relationship. However, it is unclear as to how different levels of the sensory processing pathway (i.e., perceptual, affective, or behavioral) contribute. Here, we used psychophysics to assess how alterations in tactile perception contribute to questionnaire measures of sensory reactivity, IU, and anxiety. Thirty-eight autistic children (aged 8-12 years; 27 with co-occurring ADHD) were included. Consistent with previous findings, mediation analyses showed that child-reported IU fully mediated an association between parent-reported sensory reactivity and parent-reported anxiety and that anxiety partially mediated an association between sensory reactivity and IU. Of the vibrotactile thresholds, only simultaneous frequency discrimination (SFD) thresholds correlated with sensory reactivity. Interestingly, we found that sensory reactivity fully mediated an association between SFD threshold and anxiety, and between SFD threshold and IU. Taken together, those findings suggest a mechanistic pathway whereby tactile perceptual alterations contribute to sensory reactivity at the affective level, leading in turn to increased IU and anxiety. This stepwise association can inform potential interventions for IU and anxiety in autism.

Competition among the two-plasmon decay (TPD) of backscattered light of stimulated Raman scattering (SRS), filamentation of the electron-plasma wave (EPW) and forward side SRS is investigated by two-dimensional particle-in-cell simulations. Our previous work [K. Q. Pan et al., Nucl. Fusion 58, 096035 (2018)] showed that in a plasma with the density near 1/10 of the critical density, the backscattered light would excite the TPD, which results in suppression of the backward SRS. However, this work further shows that when the laser intensity is so high ($>{10}^{16}$ W/cm2) that the backward SRS cannot be totally suppressed, filamentation of the EPW and forward side SRS will be excited. Then the TPD of the backscattered light only occurs in the early stage and is suppressed in the latter stage. Electron distribution functions further show that trapped-particle-modulation instability should be responsible for filamentation of the EPW. This research can promote the understanding of hot-electron generation and SRS saturation in inertial confinement fusion experiments.

Carbapenem-resistant gram-negative bacilli (CR-GNB) colonization screening was initiated across high-risk departments (PICU, NICU, neonatal wards, and hematology departments) in January 2017, and several CR-GNB cohort and patient-placement strategies were introduced throughout the hospital in January 2018. The colonization and infection rates decreased to varying degrees from 2017 to 2021.

A distributed UAV (unmanned aerial vehicle) flocking control method based on vision geometry is proposed, in which only monocular RGB (red, green, blue) images are used to estimate the relative positions and velocities between drones. It does not rely on special visual markers and external infrastructure, nor does it require inter-UAV communication or prior knowledge of UAV size. This method combines the advantages of deep learning and classical geometry. It adopts a deep optical flow network to estimate dense matching points between two consecutive images, uses segmentation technology to classify these matching points into background and specific UAV, and then maps the classified matching points to Euclidean space based on the depth map information. In 3D matching points, also known as 3D feature point pairs, each of their classifications is used to estimate the rotation matrix, translation vector, velocity of the corresponding UAV, as well as the relative position between drones, based on RANSAC and least squares method. On this basis, a flocking control model is constructed. Experimental results in the Microsoft Airsim simulation environment show that in all evaluation metrics, our method achieves almost the same performance as the UAV flocking algorithm based on ground truth cluster state.

Recent findings on the Reynolds-number-dependent behaviour of near-wall turbulence in terms of the ‘foot-printing’ of outer large-scale structures call for a new modelling development. A two-scale framework was proposed to couple a local fine-mesh solution with a global coarse-mesh solution by He (Intl J. Numer. Meth. Fluids, vol. 86, 2018, pp. 655–677). The methodology was implemented and demonstrated by Chen & He (J. Fluid Mech, vol. 933, 2022, p. A47) for a canonical turbulent channel flow, where the mesh-count scaling with Reynolds number is potentially reduced from $O(R{e^2})$ for a conventional wall-resolved large-eddy simulation (WRLES) to $O(R{e^1})$. The present work extends the two-scale method to turbulent boundary layers. A two-dimensional roughness element is used to trip a turbulent boundary layer. It is observed that large-scale disturbances originating at the trip have a much shorter lifetime and weaker foot-printing signatures on near-wall flow compared to those long streaky coherent structures in well-developed wall-bounded turbulent flows. Modal analyses show that the impact of trip-induced large scales can be adequately captured by a locally embedded fine-mesh block. For the tripped turbulent boundary layer, a Chebyshev block-spectral mapping is adopted to propagate source terms from the local fine-mesh blocks to the global coarse-mesh domain, driving to a target solution for the upscaled equations. The computed mean statistics and energy spectra are in good agreement with corresponding experimental data, WRLES and direct numerical simulation (DNS) results. The overall mesh count–$Re$ scaling is estimated to reduce from $O(R{e^{1.8}})$ for the full wall-resolved LES to $O(R{e^{0.9}})$ for the present two-scale solution.

The unmanned aerial vehicle (UAV) flocking among obstacles was transferred to a velocity-controllable UAV flocking problem, which means that multi-UAV gradually form and maintain the $\alpha$-lattice geometry as they track the desired flocking velocity, and can be applied to tasks such as obstacle avoidance and velocity tracking. Velocity-controllable UAV flocking problem is a multi-objective flocking controller parameters optimisation problem, for which we design flocking velocity and geometry objective function, and solve them using a multi-objective particle swarm optimisation algorithm (MOPSO). On this basis, to address the problem that MOPSO has random results and long computation time, we propose to use a neural network (NN) to approximate the mathematical relationship between the UAV flocking state and the flocking controller parameters. We simulate the flight process of 5 and 49 UAVs performing obstacle avoidance and velocity tracking tasks, respectively. The results show that the proposed UAV flocking controller has better convergence performance, obtains reproducible results, reduces computation time, and can be used for large-scale UAV flocking control.

Using 61 stories from design educators from different countries, this paper presents (1) the design competencies being fostered at different levels of education, (2) the practices (approaches, techniques, methods and tools) used to facilitate teaching and learning, (3) the ‘non-design’ competencies being fostered, and (4) the impact of COVID 19. Our findings highlight design education is not only used to teach students how to design, but also to kindle productive attitudes, behaviours and mindsets that give them the ability to address a wide range of challenges.

In October 2015, the International Agency for Research on Cancer (IARC) released a report classifying processed meat as a type 1 carcinogen. The report prompted headlines and attracted immediate public attention, but the economic impacts remain unknown. In this paper, we investigate the impacts of the IARC report on selected processed meat prices and purchases using retail scanner data from US grocery stores. We compare changes in prices and sales of selected processed meat products to a constructed synthetic control group (using a convex combination of nonmeat food products). We find a significant decrease in bacon prices in the wake of the IARC report release, but we find no evidence of a sales reduction. We find no significant changes in price and sales for ham and sausage. The pattern of price and quantity changes are consistent with downward shifts in demand and outward shifts in supply for bacon and sausage following the release of the IARC report.

Recent findings on wall-bounded turbulence have prompted a new impetus for modelling development to capture and resolve the Reynolds-number-dependent influence of outer flow on near-wall turbulence in terms of the ‘foot-printing’ of the large-scale coherent structures and the scale-interaction associated ‘modulation’. We develop a two-scale method to couple a locally embedded near-wall fine-mesh direct numerical simulation (DNS) block with a global coarser mesh domain. The influence of the large-scale structures on the local fine-mesh block is captured by a scale-dependent coarse–fine domain interface treatment. The coarse-mesh resolved disturbances are directly exchanged across the interface, while only the fine-mesh resolved fluctuations around the coarse-mesh resolved variables are subject to periodic conditions in the streamwise and spanwise directions. The global near-wall coarse-mesh region outside the local fine-mesh block is governed by the augmented flow governing equations with forcing source terms generated by upscaling the space–time-averaged fine-mesh solution. The validity and effectiveness of the method are examined for canonical incompressible channel flows at several Reynolds numbers. The mean statistics and energy spectra are in good agreement with the corresponding full DNS data. The results clearly illustrate the ‘foot-printing’ and ‘modulation’ in the local fine-mesh block. Noteworthy also is that neither spectral-gap nor scale-separation is assumed, and a smooth overlap between the global-domain and the local-domain energy spectra is observed. It is shown that the mesh-count scaling with Reynolds number is potentially reduced from $O(R{e^2})$ for the conventional fully wall-resolved large-eddy simulation (LES) to $O(Re)$ for the present locally embedded two-scale LES.

Background: Antithrombotic medications are used in the primary and secondary prevention of ischemic stroke. Previous studies have identified that up to 5.2% of ischemic strokes are associated with antithrombotic interruption, leading to significant mortality and healthcare burden. Our study aims to identify the prevalence of ischemic strokes presenting to a regional stroke centre associated with antithrombotic interruption, and to understand common reasons for medication interruption. Methods: A retrospective chart review was performed, which included 193 patients with ischemic stroke presenting to Greater Niagara General Hospital from January 2018-December 2019. Baseline demographics were recorded and patient medical records were reviewed for evidence of antithrombotic interruptions. Results: Table 1. Conclusions: Our cohort identified a significant proportion (8.3%) of ischemic strokes with documented antithrombotic interruption. Most common reasons for interruption were non-adherence and discontinuation due to previous adverse event. The results identify possible areas for improvement within patient education and safe re-initiation of antithrombotics following adverse events.

ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.