CMR provides comparable measurements of diastolic function as echocardiography.

Clinical application of cardiac magnetic resonance (CMR) is expanding but CMR assessment of LV diastolic function is still being validated. The purpose of this study was to validate assessments of left ventricular (LV) diastolic dysfunction (DD) using CMR by comparing with transthoracic echocardiography (TTE) performed on the same day. Patients with suspected or diagnosed cardiomyopathy (n = 63) and healthy volunteers (n = 24) were prospectively recruited and included in the study. CMR diastolic parameters were measured on cine images and velocity-encoded phase contrast cine images and compared with corresponding parameters measured on TTE. A contextual correlation feature tracking method was developed to calculate the mitral annular velocity curve. LV DD was classified by CMR and TTE following 2016 guidelines. Overall DD classification was 78.1% concordant between CMR and TTE (p < 0.0001). The trans-mitral inflow parameters correlated well between the two modalities (E, r = 0.78; A, r = 0.90; E/A, r = 0.82; all p < 0.0001) while the remaining diastolic parameters showed moderate correlation (e', r = 0.64; E/e', r = 0.54; left atrial volume index (LAVi), r = 0.61; all p < 0.0001). Classification of LV diastolic function by CMR showed good concordance with standardized grades established for TTE. CMR-based LV diastolic function may be integrated in routine clinical practice.Name of the registry: Technical Development of Cardiovascular Magnetic Resonance Imaging. Trial registration number: NCT00027170. Date of registration: November 26, 2001. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT00027170.

Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

Hydralazine-Associated Vasculitis and Pulmonary Hemorrhage.

Hydralazine is a potent vasodilating medication used as adjunctive therapy for the treatment of hypertension. Rarely, hydralazine may cause the development of antineutrophil cytoplasmic antibody vasculitis with the pulmonary-renal syndrome. We are presenting a case of hydralazine-associated vasculitis and pulmonary hemorrhage.

High-resolution, wavefront-sensing, full-field polarimetry of arbitrary beams using phase retrieval.

Recent advances in structured illumination are enabling a wide range of applications from imaging to metrology, which can benefit from advanced beam characterization techniques. Solving uniquely for the spatial distribution of polarization in a beam typically involves the use of two or more polarization optics, such as a polarizer and a waveplate, which is prohibitive for some wavelengths outside of the visible spectrum. We demonstrate a technique that circumvents the use of a waveplate by exploiting extended Gerchberg-Saxton phase retrieval to extract the phase. The technique enables high-resolution, wavefront-sensing, full-field polarimetry capable of solving for both simple and exotic polarization states, and moreover, is extensible to shorter wavelength light.

Subjective control of polystable illusory apparent motion: Is control possible when the stimulus affords countless motion possibilities?

We investigate whether a new polystable illusion, illusory apparent motion (IAM), is susceptible to subjective perceptual control as has been shown in other polystable stimuli (e.g., the Necker cube, apparent motion quartets). Previous research has demonstrated that, although IAM shares some properties in common with other polystable stimuli, it also has some unique ones that make it unclear whether it should have similar susceptibility to subjective control. For example, IAM can be perceived in a countless number of directions and motion patterns (e.g., up-down, left-left, contracting-expanding, shear, diagonal). To explore perceptual control of IAM, in experiment 1 (n = 99) we used a motion persistence paradigm where participants are primed with different motion patterns and are instructed to control (change or hold) the initial motion pattern and indicate when the motion pattern changes. Building on experiment 1, experiment 2 (n = 76) brings the method more in line with previous subjective control research, testing whether participants can control their perception of IAM in a context without priming and while dynamically reporting their percepts throughout the trial. Findings from the two experiments demonstrate that participants were able to control their perception of IAM across paradigms. We explore the implications of these findings, strategies reported, and open questions for future research.

Fatherhood is life changing: Uncovering structural and functional changes in the dad brain.

What are the cellular-level structural and functional changes underlying newly adaptive behaviors in the mammalian brain? In this issue of Neuron, Inada et al. (2022) identify the brain-wide connectivity and synaptic plasticity changes of hypothalamic oxytocin+ neurons in male mice contributing to their parental behaviors.

Epigenomic diversity of cortical projection neurons in the mouse brain.

Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the thalamus, superior colliculus and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.

Assessment of anthropogenic pollution by monitoring occurrence and distribution of chemicals in the river Liffey in Dublin.

This paper evaluates for the first time the spatial distribution of a wide group of organic (phthalates, nitro, aliphatic, halogen, aromatic, phenol and amino compounds) and inorganic pollutants along the Liffey river in Dublin city. The work takes into account the effect of short-term weather conditions on the occurrence of these contaminants. The results showed that rainfall conditions affect the levels of pollutants along the river in the days following a rainfall event. In addition, the tributaries entering the river Liffey were not found to impact its water quality. In relation to organic pollutants, 2,4,6-trichlorophenol, 2-nitrophenol and phthalate compounds were found in many water samples between concentrations of 0.21 and 2.17 µg L-1. On the other hand, dimethyl phthalate was present in certain samples at levels around 100 µg L-1. The levels of these contaminants in the river were lower than the toxicity values reported in the literature. Regarding inorganic pollutants, nitrates were detected from 0.59 to 6.81 mg L-1 increasing from upstream to downstream. Based on the chemical nature and applications of detected pollutants, the river contamination can be mainly related to agricultural, industrial activities as well as diffuse urban contributions. These vary with location within a short distance and have the potential to impact aquatic biodiversity as the chemical composition changes with rainfall events.

Automated Segmental Analysis of Fully Quantitative Myocardial Blood Flow Maps by First-Pass Perfusion Cardiovascular Magnetic Resonance.

First pass gadolinium-enhanced cardiovascular magnetic resonance (CMR) perfusion imaging allows fully quantitative pixel-wise myocardial blood flow (MBF) assessment, with proven diagnostic value for coronary artery disease. Segmental analysis requires manual segmentation of the myocardium. This work presents a fully automatic method of segmenting the left ventricular myocardium from MBF pixel maps, validated on a retrospective dataset of 247 clinical CMR perfusion studies, each including rest and stress images of three slice locations, performed on a 1.5T scanner. Pixel-wise MBF maps were segmented using an automated pipeline including region growing, edge detection, principal component analysis, and active contours to segment the myocardium, detect key landmarks, and divide the myocardium into sectors appropriate for analysis. Automated segmentation results were compared against a manually defined reference standard using three quantitative metrics: Dice coefficient, Cohen Kappa and myocardial border distance. Sector-wise average MBF and myocardial perfusion reserve (MPR) were compared using Pearson's correlation coefficient and Bland-Altman Plots. The proposed method segmented stress and rest MBF maps of 243 studies automatically. Automated and manual myocardial segmentation had an average (± standard deviation) Dice coefficient of 0.86 ± 0.06, Cohen Kappa of 0.86 ± 0.06, and Euclidian distances of 1.47 ± 0.73 mm and 1.02 ± 0.51 mm for the epicardial and endocardial border, respectively. Automated and manual sector-wise MBF and MPR values correlated with Pearson's coefficient of 0.97 and 0.92, respectively, while Bland-Altman analysis showed bias of 0.01 and 0.07 ml/g/min. The validated method has been integrated with our fully automated MBF pixel mapping pipeline to aid quantitative assessment of myocardial perfusion CMR.

Manuka Honey: Feasibility and Safety in Postoperative Neurosurgical Wound Care.

OBJECTIVE: To date, no reports have been published on active Leptospermum manuka honey (ALH) feasibility as a postoperative topical wound supplement in neurosurgical patients. The objective of the study is to present the authors' initial experience with using ALH in postoperative neurosurgical patients. METHODS: A single-surgeon retrospective case series review of cranial and spinal operations between 2018 and 2020 was performed in patients with nonhealing wounds or wounds deemed "at risk" as defined by grade 1 Sandy surgical wound dehiscence grading classification. An ALH gel or ointment was applied to these incisions once a day for 2 to 4 weeks. Patients were followed up in the clinic every 2 weeks until incisions had healed. RESULTS: Twenty-five postoperative patients (12 cranial, 13 spinal) were identified to be at high risk of operative debridement. All 25 patients were prescribed a topical application of ALH, which was easily adopted without patient-related adverse events. Seven (four cranial, three spinal) patients required operative debridement and treatment with long-term antibiotic therapy. CONCLUSIONS: In this small case series of neurosurgical patients who were at risk of poor wound healing, the application of medical-grade ALH was well tolerated without patient-reported adverse events. The ALH may have prevented the need for operative debridement in the majority of patients. Further prospective studies are necessary to establish its efficacy in wound healing in the neurosurgical population.

Nondestructive, high-resolution, chemically specific 3D nanostructure characterization using phase-sensitive EUV imaging reflectometry.

Next-generation nano- and quantum devices have increasingly complex 3D structure. As the dimensions of these devices shrink to the nanoscale, their performance is often governed by interface quality or precise chemical or dopant composition. Here, we present the first phase-sensitive extreme ultraviolet imaging reflectometer. It combines the excellent phase stability of coherent high-harmonic sources, the unique chemical sensitivity of extreme ultraviolet reflectometry, and state-of-the-art ptychography imaging algorithms. This tabletop microscope can nondestructively probe surface topography, layer thicknesses, and interface quality, as well as dopant concentrations and profiles. High-fidelity imaging was achieved by implementing variable-angle ptychographic imaging, by using total variation regularization to mitigate noise and artifacts in the reconstructed image, and by using a high-brightness, high-harmonic source with excellent intensity and wavefront stability. We validate our measurements through multiscale, multimodal imaging to show that this technique has unique advantages compared with other techniques based on electron and scanning probe microscopies.

Reliable segmentation of 2D cardiac magnetic resonance perfusion image sequences using time as the 3rd dimension.

OBJECTIVES: Cardiac magnetic resonance (CMR) first-pass perfusion is an established noninvasive diagnostic imaging modality for detecting myocardial ischemia. A CMR perfusion sequence provides a time series of 2D images for dynamic contrast enhancement of the heart. Accurate myocardial segmentation of the perfusion images is essential for quantitative analysis and it can facilitate automated pixel-wise myocardial perfusion quantification. METHODS: In this study, we compared different deep learning methodologies for CMR perfusion image segmentation. We evaluated the performance of several image segmentation methods using convolutional neural networks, such as the U-Net in 2D and 3D (2D plus time) implementations, with and without additional motion correction image processing step. We also present a modified U-Net architecture with a novel type of temporal pooling layer which results in improved performance. RESULTS: The best DICE scores were 0.86 and 0.90 for LV myocardium and LV cavity, while the best Hausdorff distances were 2.3 and 2.1 pixels for LV myocardium and LV cavity using 5-fold cross-validation. The methods were corroborated in a second independent test set of 20 patients with similar performance (best DICE scores 0.84 for LV myocardium). CONCLUSIONS: Our results showed that the LV myocardial segmentation of CMR perfusion images is best performed using a combination of motion correction and 3D convolutional networks which significantly outperformed all tested 2D approaches. Reliable frame-by-frame segmentation will facilitate new and improved quantification methods for CMR perfusion imaging. KEY POINTS: • Reliable segmentation of the myocardium offers the potential to perform pixel level perfusion assessment. • A deep learning approach in combination with motion correction, 3D (2D + time) methods, and a deep temporal connection module produced reliable segmentation results.

Monodisperse drops templated by 3D-structured microparticles.

The ability to create uniform subnanoliter compartments using microfluidic control has enabled new approaches for analysis of single cells and molecules. However, specialized instruments or expertise has been required, slowing the adoption of these cutting-edge applications. Here, we show that three dimensional-structured microparticles with sculpted surface chemistries template uniformly sized aqueous drops when simply mixed with two immiscible fluid phases. In contrast to traditional emulsions, particle-templated drops of a controlled volume occupy a minimum in the interfacial energy of the system, such that a stable monodisperse state results with simple and reproducible formation conditions. We describe techniques to manufacture microscale drop-carrier particles and show that emulsions created with these particles prevent molecular exchange, concentrating reactions within the drops, laying a foundation for sensitive compartmentalized molecular and cell-based assays with minimal instrumentation.

High-throughput multi-residue quantification of contaminants of emerging concern in wastewaters enabled using direct injection liquid chromatography-tandem mass spectrometry.

A rapid quantitative method for 135 contaminants of emerging concern (CECs) in untreated wastewater enabled with direct injection liquid chromatography-tandem mass spectrometry is presented. All compounds were analysed within 5 min on a short biphenyl cartridge using only 10 µL of filtered sample per injection. Up to 76 compounds were monitored simultaneously during the gradient (including mostly two transitions per compound and stable isotope-labelled analogues) while yielding >10 data points per peak. Evaluation of seven solid phase extraction sorbents showed no advantage for wastewater matrix removal. Excellent linearity, range, accuracy and precision was achieved for most compounds. Matrix effects were <11 % and detection limits were <30 ng L-1 on average. Application to untreated wastewater samples from three wastewater treatment works in the UK, USA and Mexico, enabled quantification of 56 compounds. Banned and EU 'watch-list' substances are critically discussed, including pesticides, macrolide antibiotics, diclofenac, illicit drugs as well as multiple pharmaceuticals and biocides. This high-throughput method sets a new standard for the speedy and confident determination of over a hundred CECs in wastewater at the part-per-trillion level, as demonstrated by performing over 260 injections per day.

Extraction of Distinct Neuronal Cell Types from within a Genetically Continuous Population.

Single-cell transcriptomics of neocortical neurons have revealed more than 100 clusters corresponding to putative cell types. For inhibitory and subcortical projection neurons (SCPNs), there is a strong concordance between clusters and anatomical descriptions of cell types. In contrast, cortico-cortical projection neurons (CCPNs) separate into surprisingly few transcriptomic clusters, despite their diverse anatomical projection types. We used projection-dependent single-cell transcriptomic analyses and monosynaptic rabies tracing to compare mouse primary visual cortex CCPNs projecting to different higher visual areas. We find that layer 2/3 CCPNs with different anatomical projections differ systematically in their gene expressions, despite forming only a single genetic cluster. Furthermore, these neurons receive feedback selectively from the same areas to which they project. These findings demonstrate that gene-expression analysis in isolation is insufficient to identify neuron types and have important implications for understanding the functional role of cortical feedback circuits.

Simultaneous Multi-Structure Segmentation of the Heart and Peripheral Tissues in Contrast Enhanced Cardiac Computed Tomography Angiography.

Contrast enhanced cardiac computed tomography angiography (CTA) is a prominent imaging modality for diagnosing cardiovascular diseases non-invasively. It assists the evaluation of the coronary artery patency and provides a comprehensive assessment of structural features of the heart and great vessels. However, physicians are often required to evaluate different cardiac structures and measure their size manually. Such task is very time-consuming and tedious due to the large number of image slices in 3D data. We present a fully automatic method based on a combined multi-atlas and corrective segmentation approach to label the heart and its associated cardiovascular structures. This method also automatically separates other surrounding intrathoracic structures from CTA images. Quantitative assessment of the proposed method is performed on 36 studies with a reference standard obtained from expert manual segmentation of various cardiac structures. Qualitative evaluation is also performed by expert readers to score 120 studies of the automatic segmentation. The quantitative results showed an overall Dice of 0.93, Hausdorff distance of 7.94 mm, and mean surface distance of 1.03 mm between automatically and manually segmented cardiac structures. The visual assessment also attained an excellent score for the automatic segmentation. The average processing time was 2.79 minutes. Our results indicate the proposed automatic framework significantly improves accuracy and computational speed in conventional multi-atlas based approach, and it provides comprehensive and reliable multi-structural segmentation of CTA images that is valuable for clinical application.

Assessment of Antifouling Potential of Novel Transparent Sol Gel Coatings for Application in the Marine Environment.

In recent years, there has become a growing need for the development of antifouling technology for application in the marine environment. The accumulation of large quantities of biomass on these surfaces cause substantial economic burdens within the marine industry, or adversely impact the performance of sensor technologies. Here, we present a study of transparent coatings with potential for applications on sensors or devices with optical windows. The focus of the study is on the abundance and diversity of biofouling organisms that accumulate on glass panels coated with novel transparent or opaque organically modified silicate (ORMOSIL) coatings. The diatom assessment was used to determine the effectiveness of the coatings against biofouling. Test panels were deployed in a marine environment in Galway Bay for durations of nine and thirteen months to examine differences in biofilm formation in both microfouling and macrofouling conditions. The most effective coating is one which consists of precursor, tetraethyl orthosilicate (HC006) that has a water contact angle > 100, without significant roughness (43.52 nm). However, improved roughness and wettability of a second coating, diethoxydimethylsilane (DMDEOS), showed real promise in relation to macrofouling reduction.

Differential Scanning Calorimetry to Quantify Heat-Induced Aggregation in Concentrated Protein Solutions.

Differential scanning calorimetry (DSC) is an important technique to measure the thermodynamics of protein unfolding (or folding). Information including the temperature for the onset of unfolding, the melt transition temperature (Tm), enthalpy of unfolding (ΔH), and refolding index (RI) are useful for evaluating the heat stability of proteins for a range of biochemical, structural biology, industrial, and pharmaceutical applications. We describe a procedure for careful sample preparation of proteins for DSC measurements and data analysis to determine a range of thermodynamic parameters. In particular, we highlight a measure of protein refolding following complete thermal denaturation (RI), which quantifies the proportion of protein lost to irreversible aggregation after thermal denaturation.

Fluorescence Correlation Spectroscopy for Particle Sizing in Highly Concentrated Protein Solutions.

Highly concentrated solutions of biomolecules play an increasingly important role in biopharmaceutical drug development. In these systems, the formation of reversible aggregates by self-association creates a significant analytical challenge, since dilution is often required for techniques such as HPLC/liquid chromatography and analytical ultracentrifugation. There is a growing demand for methods capable of analyzing these assemblies, ideally under formulation conditions (i.e., in the presence of excipients). One approach that addresses this need is based on fluorescence correlation spectroscopy (FCS), which is a flexible and powerful technique to measure the diffusion of fluorescently labeled particles. It is particularly suited to measuring the size distribution of reversible aggregates of proteins or peptides in highly concentrated formulations, since it overcomes some of the challenges associated with other methods. In this protocol, we describe state-of-the-art measurement and analysis of protein self-assembly by determination of particle size distributions in highly concentrated protein solutions using FCS.