Modern approaches to improving phase contrast electron microscopy

Although defocus can be used to generate partial phase contrast in transmission electron microscope images, cryo-electron microscopy (cryo-EM) can be further improved by the development of phase plates which increase contrast by applying a phase shift to the unscattered part of the electron beam. Many approaches have been investigated, including the ponderomotive interaction between light and electrons. We review the recent successes achieved with this method in high-resolution, single-particle cryo-EM. We also review the status of using pulsed or near-field enhanced laser light as alternatives, along with approaches that use scanning transmission electron microscopy (STEM) with a segmented detector rather than a phase plate

Observation of the relativistic reversal of the ponderomotive potential

The secular dynamics of a non-relativistic charged particle in an electromagnetic wave can be described by the ponderomotive potential. Although ponderomotive electron-laser interactions at relativistic velocities are important for emerging technologies from laser-based particle accelerators to laser-enhanced electron microscopy, the effects of special relativity on the interaction have only been studied theoretically. Here, we use a transmission electron microscope to measure the position-dependent phase shift imparted to a relativistic electron wave function when it traverses a standing laser wave. The kinetic energy of the electrons is varied between $80\,\mathrm{keV}$ and $300\,\mathrm{keV}$, and the laser standing wave has a continuous-wave intensity of $175\,\mathrm{GW/cm}^2$. In contrast to the non-relativistic case, we demonstrate that the phase shift depends on both the electron velocity and the wave polarization, confirming the predictions of a quasiclassical theory of the interaction. Remarkably, if the electron's speed is greater than $1/\sqrt{2}$ of the speed of light, the phase shift at the electric field nodes of the wave can exceed that at the antinodes. In this case there exists a polarization such that the phase shifts at the nodes and antinodes are equal, and the electron does not experience Kapitza-Dirac diffraction. Our results thus provide new capabilities for coherent electron beam manipulation

Random Expert Sampling for Deep Learning Segmentation of Acute Ischemic Stroke on Non-contrast CT

Purpose: Multi-expert deep learning training methods to automatically quantify ischemic brain tissue on Non-Contrast CT Materials and Methods: The data set consisted of 260 Non-Contrast CTs from 233 patients of acute ischemic stroke patients recruited in the DEFUSE 3 trial. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. We used a one-sided Wilcoxon signed-rank test on a set of segmentation metrics to compare bootstrapped point estimates of the training schemes with the inter-expert agreement and ratio of variance for consistency analysis. We further compare volumes with the 24h-follow-up DWI (final infarct core) in the patient subgroup with full reperfusion and we test volumes for correlation to the clinical outcome (mRS after 30 and 90 days) with the Spearman method. Results: Random expert sampling leads to a model that shows better agreement with experts than experts agree among themselves and better agreement than the agreement between experts and a majority-vote model performance (Surface Dice at Tolerance 5mm improvement of 61% to 0.70 +- 0.03 and Dice improvement of 25% to 0.50 +- 0.04). The model-based predicted volume similarly estimated the final infarct volume and correlated better to the clinical outcome than CT perfusion. Conclusion: A model trained on random expert sampling can identify the presence and location of acute ischemic brain tissue on Non-Contrast CT similar to CT perfusion and with better consistency than experts. This may further secure the selection of patients eligible for endovascular treatment in less specialized hospitals

Non-inferiority of Deep Learning Model to Segment Acute Stroke on Non-contrast CT Compared to Neuroradiologists

Purpose: To develop a deep learning model to segment the acute ischemic infarct on non-contrast Computed Tomography (NCCT). Materials and Methods In this retrospective study, 227 Head NCCT examinations from 200 patients enrolled in the multicenter DEFUSE 3 trial were included. Three experienced neuroradiologists (experts A, B and C) independently segmented the acute infarct on each study. The dataset was randomly split into 5 folds with training and validation cases. A 3D deep Convolutional Neural Network (CNN) architecture was optimized for the data set properties and task needs. The input to the model was the NCCT and the output was a segmentation mask. The model was trained and optimized on expert A. The outcome was assessed by a set of volume, overlap and distance metrics. The predicted segmentations of the best model and expert A were compared to experts B and C. Then we used a paired Wilcoxon signed-rank test in a one-sided test procedure for all metrics to test for non-inferiority in terms of bias and precision. Results: The best performing model reached a Surface Dice at Tolerance (SDT)5mm of 0.68 \pm 0.04. The predictions were non-inferior when compared to independent experts in terms of bias and precision (paired one-sided test procedure for differences in medians and bootstrapped standard deviations with non-inferior boundaries of -0.05, 2ml, and 2mm, p < 0.05, n=200). Conclusion: For the segmentation of acute ischemic stroke on NCCT, our 3D CNN trained with the annotations of one neuroradiologist is non-inferior when compared to two independent neuroradiologists

Accurate Estrogen Receptor Quantification in Patients with Negative and Low-Positive Estrogen-Receptor-Expressing Breast Tumors: Sub-Analyses of Data from Two Clinical Studies

<p>Full copyright for enhanced digital features is owned by the authors.</p><p> </p><p><strong>Article full text</strong></p><p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-019-0896-0"><b>here</b>.</a> <br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides</p> <p> </p

The Significance of Hair for Face Recognition

Hair is a feature of the head that frequently changes in different situations. For this reason much research in the area of face perception has employed stimuli without hair. To investigate the effect of the presence of hair we used faces with and without hair in a recognition task. Participants took part in trials in which the state of the hair either remained consistent (Same) or switched between learning and test (Switch). It was found that in the Same trials performance did not differ for stimuli presented with and without hair. This implies that there is sufficient information in the internal features of the face for optimal performance in this task. It was also found that performance in the Switch trials was substantially lower than in the Same trials. This drop in accuracy when the stimuli were switched suggests that faces are represented in a holistic manner and that manipulation of the hair causes disruption to this, with implications for the interpretation of some previous studies

Expression of Neurog1 Instead of Atoh1 Can Partially Rescue Organ of Corti Cell Survival

In the mammalian inner ear neurosensory cell fate depends on three closely related transcription factors, Atoh1 for hair cells and Neurog1 and Neurod1 for neurons. We have previously shown that neuronal cell fate can be altered towards hair cell fate by eliminating Neurod1 mediated repression of Atoh1 expression in neurons. To test whether a similar plasticity is present in hair cell fate commitment, we have generated a knockin (KI) mouse line (Atoh1KINeurog1) in which Atoh1 is replaced by Neurog1. Expression of Neurog1 under Atoh1 promoter control alters the cellular gene expression pattern, differentiation and survival of hair cell precursors in both heterozygous (Atoh1+/KINeurog1) and homozygous (Atoh1KINeurog1/KINeurog1) KI mice. Homozygous KI mice develop patches of organ of Corti precursor cells that express Neurog1, Neurod1, several prosensory genes and neurotrophins. In addition, these patches of cells receive afferent and efferent processes. Some cells among these patches form multiple microvilli but no stereocilia. Importantly, Neurog1 expressing mutants differ from Atoh1 null mutants, as they have intermittent formation of organ of Corti-like patches, opposed to a complete ‘flat epithelium’ in the absence of Atoh1. In heterozygous KI mice co-expression of Atoh1 and Neurog1 results in change in fate and patterning of some hair cells and supporting cells in addition to the abnormal hair cell polarity in the later stages of development. This differs from haploinsufficiency of Atoh1 (Pax2cre; Atoh1f/+), indicating the effect of Neurog1 expression in developing hair cells. Our data suggest that Atoh1KINeurog1 can provide some degree of functional support for survival of organ of Corti cells. In contrast to the previously demonstrated fate plasticity of neurons to differentiate as hair cells, hair cell precursors can be maintained for a limited time by Neurog1 but do not transdifferentiate as neurons

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo