Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

AI-assisted superresolution cosmological simulations

Cosmological simulations of galaxy formation are limited by finite computational resources. We draw from the ongoing rapid advances in artificial intelligence (AI; specifically deep learning) to address this problem. Neural networks have been developed to learn from high-resolution (HR) image data and then make accurate superresolution (SR) versions of different low-resolution (LR) images. We apply such techniques to LR cosmological N-body simulations, generating SR versions. Specifically, we are able to enhance the simulation resolution by generating 512 times more particles and predicting their displacements from the initial positions. Therefore, our results can be viewed as simulation realizations themselves, rather than projections, e.g., to their density fields. Furthermore, the generation process is stochastic, enabling us to sample the small-scale modes conditioning on the large-scale environment. Our model learns from only 16 pairs of small-volume LR-HR simulations and is then able to generate SR simulations that successfully reproduce the HR matter power spectrum to percent level up to 16 h−1Mpc and the HR halo mass function to within 10% down to 1011 M⊙. We successfully deploy the model in a box 1,000 times larger than the training simulation box, showing that high-resolution mock surveys can be generated rapidly. We conclude that AI assistance has the potential to revolutionize modeling of small-scale galaxy-formation physics in large cosmological volumes.

As telescopes and satellites become more powerful, observational data on galaxies, quasars, and the matter in intergalactic space becomes more detailed and covers a greater range of epochs and environments in the Universe. Our cosmological simulations (see, e.g., ref. 1) must also become more detailed and more wide-ranging in order to make predictions and test the effects of different physical processes and different dark-matter candidates. Even with supercomputers, we are forced to decide whether to maximize either resolution or volume, or else compromise on both. These limitations can be overcome through the development of methods that leverage techniques from the artificial intelligence (AI) revolution (see, e.g., ref. 2) and make superresolution (SR) simulations possible. In the present work, we begin to explore this possibility, combining knowledge and existing superscalable codes for petascale-plus cosmological simulations (3) with machine learning (ML) techniques to effectively create representative volumes of the Universe that incorporate information from higher-resolution models of galaxy formation. Our first attempts, presented here, involve simulations with dark matter and gravity only, and extensions to full hydrodynamics will follow. This hybrid approach, which will imply offloading simulations to neural networks (NNs) and other ML algorithms, has the promise to enable the prediction of quasar, supermassive black hole, and galaxy properties in a way that is statistically identical to full hydrodynamic models, but with a significant speed-up.Adding details to images below the resolution scale (SR image enhancement) has become possible with the latest advances in deep learning (DL; ML with NN; ref. 4), including generative adversarial networks (GANs; ref. 5). The technique has applications in many fields, from microscopy to law enforcement (6). It has been used for observational astronomical images by (7), to recover galaxy features from below the resolution scale in degraded Hubble Space Telescope images. Besides SR image enhancement, DL has started to find applications in cosmological simulations. For example, refs. 8 and 9 showed how NNs can predict the nonlinear formation of structures given simple linear theory predictions. NN models have also been trained to predict galaxies (10, 11) and 21-cm emission from neutral hydrogen (12) from simulations that only contain dark matter. GANs have been used in ref. 13 to generate image slices of cosmological models and to generate dark-matter halos from density fields (14). ML techniques other than DL find many applications, too. For example, Kamdar et al. (15) have applied extremely randomized trees to dark-matter simulations to predict hydrodynamic galaxy properties.Generating mocks for future sky surveys requires large volumes and high accuracy, a task that quickly becomes computationally prohibitive. To alleviate the cost, recently, Dai and Seljak (16) developed a Lagrangian-based parametric ML model to predict various hydrodynamical outputs from the dark-matter density field. In other work, Dai et al. (17, 18) sharpened the particle distribution using a potential gradient descent method starting from low-resolution (LR) simulations. Note, however, that these approaches did not aim to enhance the spatial or mass resolution of a simulation.On the DL side, recently, Ramanah et al. (19) explored using the SR technique to map density fields of LR cosmological simulations to that of the high-resolution (HR) ones. While the goal is similar, our work has the following three key differences. First, instead of focusing on the dark-matter density field, we aim to enhance the number of particles and predict their displacements, from which the density fields can be inferred. This approach allows us to preserve the particle nature of the N-body simulations and therefore to interpret the SR outputs as simulations themselves. Second, we test our technique at a higher SR ratio. Compared to ref. 19, which increased the number of Eulerian voxels by 8 times, we increase the number of particles and thus the mass resolution by a factor of 512. Finally, to facilitate future applications of SR on hydrodynamic simulations in representative volumes, we test our method at much smaller scales and in large simulations whose volume is much bigger than that of the training data.     

Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

国内住培中医患沟通研究现状的分析与思考

目的通过文献计量法分析国内住院医师规范化培训(简称住培)中关于医患沟通的研究现状,为提高住培过程中医患沟通能力提出建设性对策。方法应用文献检索策略,在中文期刊全文数据库搜索并导出自2000年1月1日—2020年2月29日以来有关住培中医患沟通的全部文献,以文献标题、发表时间和研究内容等构建Excel数据库,并进行统计分析。结果查到住培相关医患沟通的相关文献共70篇,均于2009年以后发表,文献研究数量逐年增加;文献作者所在地域分布不均匀;作者单位主要以大学附属医院为主;文献多出自于教育类、临床类和管理类期刊;文献的研究方法主要以理论论述为主,缺乏干预性研究;文献的被引次数较低,文献质量相对较差;文献的研究内容主要对医患沟通的重要性、内涵建设、现状与挑战和提高医患沟通措施方面进行了阐述。结论医患沟通培训在住培中并未受到充分重视,需在住培期间加强医患沟通教育,培养医患沟通能力,为创建新型医患关系奠定坚实的基础。     

The Preventable Productivity Burden of Kidney Disease in Australia

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Urine toxicology screening by liquid chromatography time-of-flight mass spectrometry in a quaternary hospital setting

ObjectiveValidation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC–MS method in a hospital setting.Methods217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines, barbiturates, benzodiazepines, cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC–MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method.Results42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC–MS compared to 1,267 positive findings by LC-QTOF. On average, each GC–MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC–MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites.ConclusionsThe described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory.