On the Application and Possibilities of In Vivo Microscopy in Liver Research

In vivo microscopy (IVM) provides a valuable method for studying the histophysiology of the living liver. The method allows observation of living cells in the intact organ of an anesthetized animal with an undisturbed microcirculation, at a magnification and a resolution comparable to normal light microscopy of sectioned material. Due to the absence of preparative procedures, the image differs substantially from histological sections, but it has the advantage of providing us with a reference preparation free of artifacts. In the case of the liver, we have the opportunity to observe directly such details as bile capillaries, intracellular fat droplets, lysosomes, nucleoli and different types of sinusoidal cells and blood cells. By using epifluorescence, it is possible to visualize the phagocytosis of 0.8 μm fluorescent latex (or other) particles by Kupffer cells, to observe fluorescing substances such as FITC labeled asialofetuin during the process of endocytosis and intracellular transport in parenchymal cells, and to study the behavior of specific cell types such as white blood cells which stain specifically with acridine orange. It might be expected that in the very near future, the application of modern techniques based on processing TV images, such as image intensifying, averaging, filtering, integrating, gating and others will tremendously improve the possibilities of IVM and bring it to the level of observing and following single molecules, such as FITC labelled peptide hormones and other probes, at the cellular level

Editorial: Fifty Shades of Grey: Exploring the Dark Sides of Leadership and Followership

“I could stand in the middle of Fifth Avenue and shoot somebody and I wouldn’t lose any voters. Okay. It’s like incredible!” Donald J. Trump, President of the United States, in January 2016 at a campaign rally in Iowa. In light of corporate and political turmoil and subsequent questions raised about leaders’ dark sides, this Research Topic is particularly timely. We set out to contribute to theoretical, empirical and methodological advancements, focusing on dark sides of personality, processes, and perceptions, and how they relate to leader-follower relationships. Studies of the dark side of leadership follow a long-standing tradition (Conger, 1990), and initially focused mainly on negative leader traits such as narcissism (Braun, 2017) and leader behaviors such as abusive supervision (Schyns & Schilling, 2013; Tepper, 2007; Tepper, Simon, & Park, 2017; Hogan & Kaiser, 2005). The particular potential for toxicity to unfold at the intersections of leadership and followership has been noted (Padilla, Hogan, & Kaiser, 2007), yet research into this domain remains largely underdeveloped. While followership theories receive increasing attention (Uhl-Bien, Riggio, Lowe, & Carsten, 2014), the potential dark sides of followership or followers’ impact on dark-side leaders remain unclear. Deviating from the unidimensional view that leaders are omnipotent and to be blamed for negative outcomes, we seek to place emphasis on the different ‘shades’ of dark leadership by focusing on how dark leadership can be explained by taking leaders, followers, and their interaction in specific contexts into account. In line with the purpose to explore the intersections between dark-side leadership and followership, we saw three main themes emerging from the articles published in this Research Topic. The first theme revolves around leader traits and behaviors. It focuses on questions such as what makes a ‘dark-side’ leader and what ‘dark-side’ leaders do. The second theme accounts for the interaction between leaders’ and followers’ characteristics, and zooms in on the extent to which this interaction may affect the negative impact of ‘dark-side’ leadership or followership. Finally, the articles also reflect novel ideas, extensions and integration of current theories at the interface between leadership and followership

Catering to the needs of an aging workforce : the role of employee age in the relationship between corporate social responsibility and employee satisfaction.

Contemporary organizations often reciprocate to society for using resources and for affecting stakeholders by engaging in corporate social responsibility (CSR). It has been shown that CSR has a positive impact on employee attitudes. However, not all employees may react equally strongly to CSR practices. Based on socio-emotional selectivity theory (Carstensen in Science 312:1913–1915, 2006), we contend that the effect of CSR on employee satisfaction will be more pronounced for older than for younger employees, because CSR practices address those emotional needs and goals that are prioritized when people’s future time perspective decreases. In one multi-source field study (N = 143) and one experimental study (N = 500), we demonstrate that CSR indeed has a stronger positive effect on employee satisfaction for older relative to younger employees. Accordingly, engaging in CSR can be an attractive tool for organizations that aim to keep their aging workforce satisfied with their job

Lymphoid Microenvironments in the Thymus and Lymph Node

The three-dimensional architecture of the thymus and mesenteric lymph node reveals several different stromal cell types important in the development and function of T cells. In the thymic cortex, T cells proliferate and differentiate in a meshwork of epithelial-reticular cells. They then migrate towards the medulla where they may interact with interdigitating cells. T cells migrate from the thymus through perivascular spaces, surrounding large vessels at the cortico-medullary boundary. In this area also large thymic cystic cavities are found, their function remains at present unclear. Mature selected T cells leave the thymus most probably by the venous bloodstream, to enter peripheral lymph nodes. Upon entering the lymph node they cross the wall of high endothelial venules. On the other hand, lymph enters the node by afferent lymphatics draining into various types of sinuses. Here, macrophages are strategically located to phagocytose and process antigen. These cells then expose antigen to T cells and B cells within the lymph node parenchyma, thus creating a microenvironment for the onset of an immune response. The various microenvironments important in T cell development and T cell function are shown in this paper using scanning electron microscopy as a dissecting tool. We discuss our morphological findings in the light of recent data on the physiology of T cell differentiation and function

Introducing e-health technology to routine cataract care:patient perspectives on web-based eye test for postoperative telemonitoring

Purpose:To explore cataract patients' experiences with an e-health tool for self-assessing visual function (ie, a web-based eye test), and to formulate recommendations for its successful adoption in routine cataract care.Setting:Clinics in the Netherlands, Germany, and Austria.Design:Mixed-methods study.Methods:22 participants were included in this study; in-depth interviews were conducted with 12. Questionnaires and in-depth semi-structured interviews were conducted alongside a multicenter randomized controlled trial evaluating the validity, safety and cost-effectiveness of remote care after cataract surgery (Cataract Online Refraction Evaluation, a Randomized Controlled Trial). Results were analyzed thematically.Results:Participants reported positively about performing the web-based eye test at home. 4 overarching themes were identified in the interviews. First, participants were inventive in overcoming practical barriers encountered while conducting the test. Second, participants desired a clear presentation of test results and their meaning. Third, the ability to self-monitor visual function was appreciated. Fourth, most participants preferred to keep the option to contact their eyecare professional (ECP) postoperatively, especially when experiencing symptoms. Most would be satisfied with a phone consultation or an e-consult. Participants reported positive experiences with the web-based eye test. Barriers for successful adoption were identified, including insecurity about correctly performing the test, incomplete information on how to interpret test results, and a feeling that in-hospital assessments were superior to remote assessments.Conclusions:It is recommended to focus on building trust in remote eyecare delivery and that access to the ECP be retained when medically indicated or deemed necessary by the patient.</p

Improved filtering methods to suppress cardiovascular contamination in electrical impedance tomography recordings

Objective. Electrical impedance tomography (EIT) produces clinical useful visualization of the distribution of ventilation inside the lungs. The accuracy of EIT-derived parameters can be compromised by the cardiovascular signal. Removal of these artefacts is challenging due to spectral overlapping of the ventilatory and cardiovascular signal components and their time-varying frequencies. We designed and evaluated advanced filtering techniques and hypothesized that these would outperform traditional low-pass filters. Approach. Three filter techniques were developed and compared against traditional low-pass filtering: multiple digital notch filtering (MDN), empirical mode decomposition (EMD) and the maximal overlap discrete wavelet transform (MODWT). The performance of the filtering techniques was evaluated (1) in the time domain (2) in the frequency domain (3) by visual inspection. We evaluated the performance using simulated contaminated EIT data and data from 15 adult and neonatal intensive care unit patients. Main result. Each filter technique exhibited varying degrees of effectiveness and limitations. Quality measures in the time domain showed the best performance for MDN filtering. The signal to noise ratio was best for DLP, but at the cost of a high relative and removal error. MDN outbalanced the performance resulting in a good SNR with a low relative and removal error. MDN, EMD and MODWT performed similar in the frequency domain and were successful in removing the high frequency components of the data. Significance. Advanced filtering techniques have benefits compared to traditional filters but are not always better. MDN filtering outperformed EMD and MODWT regarding quality measures in the time domain. This study emphasizes the need for careful consideration when choosing a filtering approach, depending on the dataset and the clinical/research question.</p

Improved filtering methods to suppress cardiovascular contamination in electrical impedance tomography recordings

Objective. Electrical impedance tomography (EIT) produces clinical useful visualization of the distribution of ventilation inside the lungs. The accuracy of EIT-derived parameters can be compromised by the cardiovascular signal. Removal of these artefacts is challenging due to spectral overlapping of the ventilatory and cardiovascular signal components and their time-varying frequencies. We designed and evaluated advanced filtering techniques and hypothesized that these would outperform traditional low-pass filters. Approach. Three filter techniques were developed and compared against traditional low-pass filtering: multiple digital notch filtering (MDN), empirical mode decomposition (EMD) and the maximal overlap discrete wavelet transform (MODWT). The performance of the filtering techniques was evaluated (1) in the time domain (2) in the frequency domain (3) by visual inspection. We evaluated the performance using simulated contaminated EIT data and data from 15 adult and neonatal intensive care unit patients. Main result. Each filter technique exhibited varying degrees of effectiveness and limitations. Quality measures in the time domain showed the best performance for MDN filtering. The signal to noise ratio was best for DLP, but at the cost of a high relative and removal error. MDN outbalanced the performance resulting in a good SNR with a low relative and removal error. MDN, EMD and MODWT performed similar in the frequency domain and were successful in removing the high frequency components of the data. Significance. Advanced filtering techniques have benefits compared to traditional filters but are not always better. MDN filtering outperformed EMD and MODWT regarding quality measures in the time domain. This study emphasizes the need for careful consideration when choosing a filtering approach, depending on the dataset and the clinical/research question.</p

Regional Deep Atrophy: a Self-Supervised Learning Method to Automatically Identify Regions Associated With Alzheimer's Disease Progression From Longitudinal MRI

Longitudinal assessment of brain atrophy, particularly in the hippocampus, is a well-studied biomarker for neurodegenerative diseases, such as Alzheimer's disease (AD). In clinical trials, estimation of brain progressive rates can be applied to track therapeutic efficacy of disease modifying treatments. However, most state-of-the-art measurements calculate changes directly by segmentation and/or deformable registration of MRI images, and may misreport head motion or MRI artifacts as neurodegeneration, impacting their accuracy. In our previous study, we developed a deep learning method DeepAtrophy that uses a convolutional neural network to quantify differences between longitudinal MRI scan pairs that are associated with time. DeepAtrophy has high accuracy in inferring temporal information from longitudinal MRI scans, such as temporal order or relative inter-scan interval. DeepAtrophy also provides an overall atrophy score that was shown to perform well as a potential biomarker of disease progression and treatment efficacy. However, DeepAtrophy is not interpretable, and it is unclear what changes in the MRI contribute to progression measurements. In this paper, we propose Regional Deep Atrophy (RDA), which combines the temporal inference approach from DeepAtrophy with a deformable registration neural network and attention mechanism that highlights regions in the MRI image where longitudinal changes are contributing to temporal inference. RDA has similar prediction accuracy as DeepAtrophy, but its additional interpretability makes it more acceptable for use in clinical settings, and may lead to more sensitive biomarkers for disease monitoring in clinical trials of early AD.Comment: Submitted to NeuroImage for revie

Hippocampal T2 hyperintensities on 7Tesla MRI

AbstractHippocampal focal T2 hyperintensities (HT2Hs), also referred to as hippocampal sulcal cavities, are a common finding on Magnetic Resonance (MR) images. There is uncertainty about their etiology and clinical significance. In this study we aimed to describe these HT2Hs in more detail using high resolution 7Tesla MR imaging, addressing 1) the MR signal characteristics of HT2Hs, 2) their occurrence frequency, 3) their location within the hippocampus, and 4) their relation with age. We also performed an explorative post-mortem study to examine the histology of HT2Hs.Fifty-eight persons without a history of invalidating neurological or psychiatric disease (mean age 64±8years; range 43–78years), recruited through their general practitioners, were included in this study. They all underwent 7Tesla MRI, including a T1, T2, and FLAIR image. MR signal characteristics of the HT2Hs were assessed on these images by two raters. Also, the location and number of the HT2Hs were assessed. In addition, four formalin-fixed brain slices from two subjects were scanned overnight. HT2Hs identified in these slices were subjected to histopathological analysis.HT2Hs were present in 97% of the subjects (median number per person 10; range 0–20). All HT2Hs detected on the T2 sequence were hypointense on T1 weighted images. Of all HT2Hs, 94% was hypointense and 6% hyperintense on FLAIR. FLAIR hypointense HT2Hs were all located in the vestigial sulcus of the hippocampus, FLAIR hyperintense HT2Hs in the hippocampal sulcus or the gray matter. Post-mortem MRI and histopathological analysis suggested that the hypointense HT2Hs on FLAIR were cavities filled with cerebrospinal fluid. A hyperintense HT2H on FLAIR proved to be a microinfarct upon microscopy.In conclusion, hippocampal T2Hs are extremely common and unrelated to age. They can be divided into two types (hypo- and hyperintense on FLAIR), probably with different etiology