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Abstract Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual’s distinct endophenotype.

Background/Aims Staffing represents the most significant cost to the National Health Service, and ophthalmology is its largest outpatient specialty. Value-based healthcare (VBH) focuses on care processes. Innovative models include a shift towards ‘virtual’ glaucoma services. We used VBH costing methodology to quantify personnel costs of virtual and face-to-face (F2F) glaucoma clinics.Methods Virtual and F2F clinics were process-mapped to produce step-by-step pathways of patients in each setting. Real-world timings were then audited, and time-driven activity-based costing was used to calculate the personnel cost-per-patient for both settings.Results Data were captured from 24 consecutive virtual glaucoma patients and 42 consecutive patients across two F2F clinics. The capacity cost rates in £/min were £0.24 for technicians and £1.16 for consultants. The average time taken to acquire clinical data in the virtual pathway was 39 min per patient (95% CI 36 to 43, range 27–61) with 14 min (95% CI 13 to 14, range 12–20) for their remote consultant review. The estimated personnel costs associated with a single virtual glaucoma clinic visit totalled £25.60 (95% CI £23.72 to £33.52). The average time taken to be seen in the F2F clinic was 50 min (95% CI 42 to 59 min, range 12–123 min) with a personnel cost of £31.08 (95% CI £19.70-£42.43).Conclusion Staff costs associated with visits to the consultant-delivered virtual and F2F glaucoma clinics were similar (p value=0.14), supporting virtual clinics to provide service capacity. The main limitations were that our study involved a single site, small sample size and did not consider the severity of glaucoma.

Abstract In this report, the advanced manufacturing advantages of using supersaturated chlorinated chemistry are demonstrated at 1550 °C in 4H‐silicon carbide (4H‐SiC) epitaxy on trenches with different geometric profiles. Sloped mesa sidewalls (8°) show improved filling behavior compared with vertical sidewalls (2°) and lower the optimum chlorine/silicon ratio (Si:Cl) required to complete filling. Both the optimum Cl:Si ratio (10) and sidewall angle are lower for wider trench openings, allowing complete fill of 3 µm wide trenches (8 µm pitch, 5 µm depth) at a filling rate of 19 µm h−1. Excessive hydrogen chloride (HCl) diminishes filling by reducing sidewall growth and can also produce an end surface with very rough topography. This work demonstrates the importance of trench geometry on both the filling behavior and process optimization in chlorinated trench filling epitaxy for the manufacture of 4H‐SiC superjunction power electronics.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform – optically pumped magnetometer-based magnetoencephalography (OPM-MEG) – to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

The ability to collect high-quality neuroimaging data during ambulatory participant movement would enable a wealth of neuroscientific paradigms. Wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has the potential to allow participant movement during a scan. However, the strict zero magnetic field requirement of OPMs means that systems must be operated inside a magnetically shielded room (MSR) and also require active shielding using electromagnetic coils to cancel residual fields and field changes (due to external sources and sensor movements) that would otherwise prevent accurate neuronal source reconstructions. Existing active shielding systems only compensate fields over small, fixed regions and do not allow ambulatory movement. Here we describe the matrix coil, a new type of active shielding system for OPM-MEG which is formed from 48 square unit coils arranged on two planes which can compensate magnetic fields in regions that can be flexibly placed between the planes. Through the integration of optical tracking with OPM data acquisition, field changes induced by participant movement are cancelled with low latency (25 ms). High-quality MEG source data were collected despite the presence of large (65 cm translations and 270° rotations) ambulatory participant movements.

Abstract Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40–60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a ‘window coil’ active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.

Optically pumped magnetometers (OPMs) are an emerging lightweight and compact sensor that can measure magnetic fields generated by the human brain. OPMs enable construction of wearable magnetoencephalography (MEG) systems, which offer advantages over conventional instrumentation. However, when trying to measure signals at low frequency, higher levels of inherent sensor noise, magnetic interference and movement artefact introduce a significant challenge. Accurate characterisation of low frequency brain signals is important for neuroscientific, clinical, and paediatric MEG applications and consequently, demonstrating the viability of OPMs in this area is critical. Here, we undertake measurement of theta band (4–8 Hz) neural oscillations and contrast a newly developed 174 channel triaxial wearable OPM-MEG system with conventional (cryogenic-MEG) instrumentation. Our results show that visual steady state responses at 4 Hz, 6 Hz and 8 Hz can be recorded using OPM-MEG with a signal-to-noise ratio (SNR) that is not significantly different to conventional MEG. Moreover, we measure frontal midline theta oscillations during a 2-back working memory task, again demonstrating comparable SNR for both systems. We show that individual differences in both the amplitude and spatial signature of induced frontal-midline theta responses are maintained across systems. Finally, we show that our OPM-MEG results could not have been achieved without a triaxial sensor array, or the use of postprocessing techniques. Our results demonstrate the viability of OPMs for characterising theta oscillations and add weight to the argument that OPMs can replace cryogenic sensors as the fundamental building block of MEG systems.

Abstract Objective Stereoelectroencephalography (sEEG) is an intracranial encephalography method of expanding use. The need for increased epilepsy surgery access has led to the consideration of sEEG adoption by new or expanding surgical epilepsy programs. Data regarding safety and efficacy are uncommon outside of high‐volume, well‐established centers, which may be less applicable to newer or low‐volume centers. The objective of this study was to add to the sEEG outcomes in the literature from the perspective of a rapidly expanding center. Methods A retrospective chart review of consecutive sEEG cases from January 2016 to December 2019 was performed. Data extraction included demographic data, surgical data, and outcome data, which pertinently examined surgical method, progression to therapeutic procedure, clinically significant adverse events, and Engel outcomes. Results One hundred and fifty‐two sEEG procedures were performed on 131 patients. Procedures averaged 10.5 electrodes for a total of 1603 electrodes. The majority (84%) of patients progressed to a therapeutic procedure. Six clinically significant complications occurred: three retained electrodes, two hemorrhages, and one failure to complete investigation. Only one complication resulted in a permanent deficit. Engel 1 outcome was achieved in 63.3% of patients reaching one‐year follow‐up after a curative procedure. Significance New or expanding epilepsy surgery centers can appropriately consider the use of sEEG. The complication rate is low and the majority of patients progress to therapeutic surgery. Procedural safety, progression to therapeutic intervention, and Engel outcomes are comparable to cohorts from long‐established epilepsy surgery programs.

The evolution of human cognitive function is reliant on complex social interactions which form the behavioural foundation of who we are. These social capacities are subject to dramatic change in disease and injury; yet their supporting neural substrates remain poorly understood. Hyperscanning employs functional neuroimaging to simultaneously assess brain activity in two individuals and offers the best means to understand the neural basis of social interaction. However, present technologies are limited, either by poor performance (low spatial/temporal precision) or an unnatural scanning environment (claustrophobic scanners, with interactions via video). Here, we describe hyperscanning using wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs). We demonstrate our approach by simultaneously measuring brain activity in two subjects undertaking two separate tasks—an interactive touching task and a ball game. Despite large and unpredictable subject motion, sensorimotor brain activity was delineated clearly, and the correlation of the envelope of neuronal oscillations between the two subjects was demonstrated. Our results show that unlike existing modalities, OPM-MEG combines high-fidelity data acquisition and a naturalistic setting and thus presents significant potential to investigate neural correlates of social interaction.

Magnetoencephalography (MEG) has been revolutionised by optically pumped magnetometers (OPMs). “OPM-MEG” offers higher sensitivity, better spatial resolution, and lower cost than conventional instrumentation based on superconducting quantum interference devices (SQUIDs). Moreover, because OPMs are small, lightweight, and portable they offer the possibility of lifespan compliance and (with control of background field) motion robustness, dramatically expanding the range of MEG applications. However, OPM-MEG remains nascent technology; it places stringent requirements on magnetic shielding, and whilst a number of viable systems exist, most are custom made and there have been no cross-site investigations showing the reliability of data. In this paper, we undertake the first cross-site OPM-MEG comparison, using near identical commercial systems scanning the same participant. The two sites are deliberately contrasting, with different magnetic environments: a “green field” campus university site with an OPM-optimised shielded room (low interference) and a city centre hospital site with a “standard” (non-optimised) MSR (higher interference). We show that despite a 20-fold difference in background field, and a 30-fold difference in low frequency interference, using dynamic field control and software-based suppression of interference we can generate comparable noise floors at both sites. In human data recorded during a visuo-motor task and a face processing paradigm, we were able to generate similar data, with source localisation showing that brain regions could be pinpointed with just ∼10 mm spatial discrepancy and temporal correlations of > 80%. Overall, our study demonstrates that, with appropriate field control, OPM-MEG systems can be sited even in city centre hospital locations. The methods presented pave the way for wider deployment of OPM-MEG.

Optically-pumped magnetometers (OPMs) are an established alternative to superconducting sensors for magnetoencephalography (MEG), offering significant advantages including flexibility to accommodate any head size, uniform coverage, free movement during scanning, better data quality and lower cost. However, OPM sensor technology remains under development; there is flexibility regarding OPM design and it is not yet clear which variant will prove most effective for MEG. Most OPM-MEG implementations have either used single-axis (equivalent to conventional MEG) or dual-axis magnetic field measurements. Here we demonstrate use of a triaxial OPM formulation, able to characterise the full 3D neuromagnetic field vector. We show that this novel sensor is able to characterise magnetic fields with high accuracy and sensitivity that matches conventional (dual-axis) OPMs. We show practicality via measurement of biomagnetic fields from both the heart and the brain. Using simulations, we demonstrate how triaxial measurement offers improved cortical coverage, especially in infants. Finally, we introduce a new 3D-printed child-friendly OPM-helmet and demonstrate feasibility of triaxial measurement in a five-year-old. In sum, the data presented demonstrate that triaxial OPMs offer a significant improvement over dual-axis variants and are likely to become the sensor of choice for future MEG systems, particularly for deployment in paediatric populations.

Microorganisms play a critical role in the structure and functioning of soil ecosystems. Within acidic soil across the northeastern United States and Canada, we have little understanding of the microbial diversity present and its relationship to the biochemical cycles. The current study is aimed at understanding the taxonomical and functional diversities in the acidic soil obtained from near various types of trees, how the diversities change as a function of depth, and the linkage between taxonomical and functional diversities. From eight sampling locations, soil samples were collected from three horizons (depths). The three depths were 0–10 cm (A), 11–25 cm (B), and 26–40 cm (C). Results indicate that across all the samples analyzed, Bradyrhizobium and Candidatus Solibacter are the most abundant bacteria in the soil microbiome. The differences in the soil microbiome across the samples were attributed to the abundance of individual organism’s present in the soil and not to the presence or absence of individual organisms. Subsystem level analysis of the soil microbiome sequences indicate that there is higher level of abundance of genes attributed to regulation and cell signaling. A low level of sequences were detected for sulfur metabolism, potassium metabolism, iron acquisition and metabolism, and phosphorous metabolism. Structure-functional analysis indicate that Bradyrhizobium, Rhodopseudomonas, and Burkholderia are the major organisms involved in the nutritional ecosystem functioning within acidic soil. Based on the results, we propose utilizing a consortium of these organisms as an environmentally friendly alternative to the use of chemicals to maintain soil fertility and ecosystem functioning.

Electrodiagnosis is routinely integrated into clinical neurophysiology practice for peripheral nerve disease diagnoses, such as neuropathy, demyelinating disorders, nerve entrapment/impingement, plexopathy, or radiculopathy. Measured with conventional surface electrodes, the propagation of peripheral nerve action potentials along a nerve is the result of ionic current flow which, according to Ampere’s Law, generates a small magnetic field that is also detected as an “action current” by magnetometers, such as superconducting quantum interference device (SQUID) Magnetoencephalography (MEG) systems. Optically pumped magnetometers (OPMs) are an emerging class of quantum magnetic sensors with a demonstrated sensitivity at the 1 fT/√Hz level, capable of cortical action current detection. But OPMs were ostensibly constrained to low bandwidth therefore precluding their use in peripheral nerve electrodiagnosis. With careful OPM bandwidth characterization, we hypothesized OPMs may also detect compound action current signatures consistent with both Sensory Nerve Action Potential (SNAP) and the Hoffmann Reflex (H-Reflex). In as much, our work confirms OPMs enabled with expanded bandwidth can detect the magnetic signature of both the SNAP and H-Reflex. Taken together, OPMs now show potential as an emerging electrodiagnostic tool.

Objective: This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation. Data Synthesis: The literature search to identify clinical trials returned only the CHRYSALIS phase 1 study. In a phase I trial, amivantamab-vmjw was associated with an overall response rate (ORR) of 40% (95% CI, 29–51) in the EGFR exon20ins NSCLC patient population (n = 81) after platinum-based chemotherapy. There were 3 complete responses (CRs) and 29 partial responses (PRs). The median duration of response (DOR) was 11.1 months (95% CI, 6.9—not reached; NR). The median progression-free survival (PFS) was 8.3 months (95% CI, 6.5–10.9), and overall survival (OS) was 22.8 months (95% CI, 14.6—NR). Application to Clinical Practice: This review summarizes the pharmacology, clinical evidence, and use of amivantamab-vmjw for patients with locally advanced or metastatic NSCLC with EGFR exon20ins mutation. Conclusion: The FDA approval of amivantamab-vmjw, the first bispecific antibody to target the exon20ins mutation, represents an important advancement in the treatment of patients with NSCLC with limited effective treatment options. The initial findings of the CHRYSALIS trial demonstrate an overall tumor response benefit with an acceptable safety profile.

Optically-pumped magnetometers (OPMs) are highly sensitive, compact magnetic field sensors, which offer a viable alternative to cryogenic sensors (superconducting quantum interference devices – SQUIDs) for magnetoencephalography (MEG). With the promise of a wearable system that offers lifespan compliance, enables movement during scanning, and provides higher quality data, OPMs could drive a step change in MEG instrumentation. However, this potential can only be realised if background magnetic fields are appropriately controlled, via a combination of optimised passive magnetic screening (i.e. enclosing the system in layers of high-permeability materials), and electromagnetic coils to further null the remnant magnetic field. In this work, we show that even in an OPM-optimised passive shield with extremely low (

The optically pumped magnetometer (OPM) is a viable means to detect magnetic fields generated by human brain activity. Compared to conventional detectors (superconducting quantum interference devices) OPMs are small, lightweight, flexible, and operate without cryogenics. This has led to a step change in instrumentation for magnetoencephalography (MEG), enabling a “wearable” scanner platform, adaptable to fit any head size, able to acquire data whilst subjects move, and offering improved data quality. Although many studies have shown the efficacy of ‘OPM-MEG’, one relatively untapped advantage relates to improved array design. Specifically, OPMs enable the simultaneous measurement of magnetic field components along multiple axes (distinct from a single radial orientation, as used in most conventional MEG systems). This enables characterisation of the magnetic field vector at all sensors, affording extra information which has the potential to improve source reconstruction. Here, we conduct a theoretical analysis of the critical parameters that should be optimised for effective source reconstruction. We show that these parameters can be optimised by judicious array design incorporating triaxial MEG measurements. Using simulations, we demonstrate how a triaxial array offers a dramatic improvement on our ability to differentiate real brain activity from sources of magnetic interference (external to the brain). Further, a triaxial system is shown to offer a marked improvement in the elimination of artefact caused by head movement. Theoretical results are supplemented by an experimental recording demonstrating improved interference reduction. These findings offer new insights into how future OPM-MEG arrays can be designed with improved performance.

The ability of the microbiota present in agricultural soil to recover post-flooding is not known. In the current project, sandy loam and planting soil were flooded for various time points and after flooding, incubated for three weeks. The bacterial communities in the soil samples were analyzed using the Illumina Miseq® platform. Statistical analysis of the microbiota between the control and flooded soil show that there is no statistical difference between the two (p > 0.05). Total richness in the control and flooded soil were also compared. Again, no statistical difference was observed (p > 0.05). Based on the observed results, we conclude that the microbiota in the soil is very resilient to flooding and can recover within three weeks of incubation.

Magnetoencephalography (MEG) recordings are sensitive to movement and therefore are especially challenging with young participants. Here the authors develop a wearable MEG system based on a modified bicycle helmet, which enables reliable recordings in toddlers, children, teenagers and adults.

Optically-pumped magnetometers (OPMs) offer the potential for a step change in magnetoencephalography (MEG) enabling wearable systems that provide improved data quality, accommodate any subject group, allow data capture during movement and potentially reduce cost. However, OPM-MEG is a nascent technology and, to realise its potential, it must be shown to facilitate key neuroscientific measurements, such as the characterisation of brain networks. Networks, and the connectivities that underlie them, have become a core area of neuroscientific investigation, and their importance is underscored by many demonstrations of their disruption in brain disorders. Consequently, a demonstration of network measurements using OPM-MEG would be a significant step forward. Here, we aimed to show that a wearable 50-channel OPM-MEG system enables characterisation of the electrophysiological connectome. To this end, we measured connectivity in the resting state and during a visuo-motor task, using both OPM-MEG and a state-of-the-art 275-channel cryogenic MEG device. Our results show that resting-state connectome matrices from OPM and cryogenic systems exhibit a high degree of similarity, with correlation values >70%. In addition, in task data, similar differences in connectivity between individuals (scanned multiple times) were observed in cryogenic and OPM-MEG data, again demonstrating the fidelity of the OPM-MEG device. This is the first demonstration of network connectivity measured using OPM-MEG, and results add weight to the argument that OPMs will ultimately supersede cryogenic sensors for MEG measurement.

Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependant task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus.

Objective To ascertain patient acceptance of immediate sequential bilateral cataract surgery (ISBCS) in the National Health Service (NHS).Methods A survey was devised using a 5-point Likert scale for questions related to ISBCS, which patients undertook during their cataract outpatient appointment pre-COVID-19 lockdown and by telephone during the lockdown.Results Questionnaires were completed for 267 patients. Most respondents were aged over 71 (51%) and were female individuals (60%). Forty-five per cent agreed/strongly agreed with opting for ISBCS. A positive correlation was identified between opting for ISBCS and convenience to the patient (r=0.76, p

Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however, such systems have fundamental limitations. In recent years, non-cryogenic quantum-enabled sensors, called optically-pumped magnetometers (OPMs), in combination with novel techniques for accurate background magnetic field control, have promised to lift those restrictions offering an adaptable, motion-robust MEG system, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging.

Summary: The human intestinal mucosa is a critical site for absorption, distribution, metabolism, and excretion (ADME)/Tox studies in drug development and is difficult to recapitulate in vitro. Using bioprinting, we generated three-dimensional (3D) intestinal tissue composed of human primary intestinal epithelial cells and myofibroblasts with architecture and function to model the native intestine. The 3D intestinal tissue demonstrates a polarized epithelium with tight junctions and specialized epithelial cell types and expresses functional and inducible CYP450 enzymes. The 3D intestinal tissues develop physiological barrier function, distinguish between high- and low-permeability compounds, and have functional P-gp and BCRP transporters. Biochemical and histological characterization demonstrate that 3D intestinal tissues can generate an injury response to compound-induced toxicity and inflammation. This model is compatible with existing preclinical assays and may be implemented as an additional bridge to clinical trials by enhancing safety and efficacy prediction in drug development. : In Vitro Toxicology Including 3D Culture; Bioengineering; Tissue Engineering Subject Areas: In Vitro Toxicology Including 3D Culture, Bioengineering, Tissue Engineering

Background Fetal magnetocardiography (fMCG) is a highly effective technique for evaluation of fetuses with life‐threatening arrhythmia, but its dissemination has been constrained by the high cost and complexity of Superconducting Quantum Interference Device (SQUID) instrumentation. Optically pumped magnetometers (OPMs) are a promising new technology that can replace SQUIDs for many applications. This study compares the performance of an fMCG system, utilizing OPMs operating in a person‐sized magnetic shield, to that of a conventional fMCG system, utilizing SQUID magnetometers operating in a magnetically shielded room. Methods and Results fMCG recordings were made in 24 subjects using the SQUID system with the mother lying supine in a magnetically shielded room and the OPM system with the mother lying prone in a person‐sized, cylindrical shield. Signal‐to‐noise ratios of the OPM and SQUID recordings were not statistically different and were adequate for diagnostic purposes with both technologies. Although the environmental noise was higher using the small open‐ended shield, this was offset by the higher signal amplitude achieved with prone positioning, which reduced the distance between the fetus and sensors and improved patient comfort. In several subjects, fMCG provided a differential diagnosis that was more precise and/or definitive than was possible with echocardiography alone. Conclusions The OPM‐based system was portable, improved patient comfort, and performed as well as the SQUID‐based system at a small fraction of the cost. Electrophysiological assessment of fetal rhythm is now practical and will have a major impact on management of fetuses with long QT syndrome and other life‐threatening arrhythmias.

Northern populations of Arctic char (Salvelinus alpinus) can be anadromous, migrating annually from the ocean to freshwater lakes and rivers in order to escape sub-zero temperatures. Such seasonal behavior demands that these fish and their associated microbiomes adapt to changes in salinity, temperature, and other environmental challenges. We characterized the microbial community composition of anadromous S. alpinus, netted by Inuit fishermen at freshwater and seawater fishing sites in the high Arctic, both under ice and in open water. Bacterial profiles were generated by DNA extraction and high-throughput sequencing of PCR-amplified 16S ribosomal RNA genes. Results showed that microbial communities on the skin and intestine of Arctic char were statistically different when sampled from freshwater or saline water sites. This association was tested using hierarchical Ward's linkage clustering, showing eight distinct clusters in each of the skin and intestinal microbiomes, with the clusters reflecting sampling location between fresh and saline environments, confirming a salinity-linked turnover. This analysis also provided evidence for a core composition of skin and intestinal bacteria, with the phyla Proteobacteria, Firmicutes, and Cyanobacteria presenting as major phyla within the skin-associated microbiomes. The intestine-associated microbiome was characterized by unidentified genera from families Fusobacteriaceae, Comamonadaceae, Pseudomonadaceae, and Vibrionaceae. The salinity-linked turnover was further tested through ordinations that showed samples grouping based on environment for both skin- and intestine-associated microbiomes. This finding implies that core microbiomes between fresh and saline conditions could be used to assist in regulating optimal fish health in aquaculture practices. Furthermore, identified taxa from known psychrophiles and with nitrogen cycling properties suggest that there is additional potential for biotechnological applications for fish farm and waste management practices.

In an era when education is supposed to be a means for good jobs and linked to extrinsic values such as fame and money, students are losing interest in school education. The goal of this research is to see if there is any correlation between the students' views of school worthiness and schoolwork, and demographic variables. Our hypothesis is that several key demographics involving diversity, income, and education will affect how students view school and its importance. Results show that there is no correlation between the demographic variables we analyzed and the student perception of school worthiness.

Objective. The purpose of the study is to extend research on patient satisfaction with telemedicine services by employing the theoretical framework of Expectation Disconfirmation Theory (EDT) for diabetic retinopathy screenings focusing on rural patients. Method. Adult subjects (n=220) with diabetes were recruited from a single family practice office in rural Iowa. Subjects completed a “pre” survey concerning their forward-looking perceptions of telemedicine prior to using telemedicine for detection of diabetic retinopathy and a “post” survey after they received recommendations from the distant ophthalmologists. Results. All hypotheses of the EDT model were supported. Patient satisfaction is influenced by both patients’ expectations (P

The sheer volume of data being generated by the resources is creating a form of cognitive overload for enterprises. The data will be useful to multiple processes in enterprises. Learning and understanding natural language for each process increases computer work in the organization. Enterprise Cognitive Computing (ECC) with the help of Semantic Technology generates structured and organized data for accurate decision making in enterprises. For developing ECC system there are many implementation challenges that need to resolve. ECC comprises Machine Learning, Artificial Intelligence and Question Answering machine that uses natural language processing technologies. These emerging technologies need to customize or combined with complementary solutions as semantic knowledge graphs, depending on the use case. This paper addresses problems of Enterprises that use unstructured data and how this problem can be resolved using semantic technology tools.

Purpose. Congenital retinal macrovessels (CRM) represent rare aberrant vasculature of the retinal vessels that can supply or drain the macula. In this report, the optical coherence tomography angiography features of a congenital retinal macrovessel are discussed. Methods. The history and examination findings are presented alongside swept-source OCT angiography with corresponding B scan and en face OCT imaging. Patients. The case is a 12-year-old female patient with excellent best-corrected visual acuity in both eyes. Results. Swept-source OCT angiography demonstrated considerable loss of the foveal avascular zone at the levels of the superficial and deep capillary plexus. Discussion. In this case there was no detrimental effect on vision despite anatomical loss of the foveal avascular zone.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tophi are the visible dermatological signs of gout. A case of tophaceous gout in a middle-aged man with no other metabolic derangement is being presented with multiple tophi on the hands and feet overlying joints as well as on the fingers and toes. We thought it to be of educational value to demonstrate needle-like crystals of urate by polarizing microscopy. X-rays of hands and feet showed dramatic destructive changes. The patient presented with mottled hypopigmentation on anterior and posterior knees and dorsa of hands and feet where he applied hot "aankda" leaves and covered them with bandage resulting in irritant dermatitis with postinflammatory hypopigmentation. This proved to be a red herring in this case.

The impact of silver nanoparticles (NPs) and microparticles (MPs) on bacterial and fungal assemblages was studied in soils collected from a low arctic site. Two different concentrations (0.066% and 6.6%) of Ag NPs and Ag MPs were tested in microcosms that were exposed to temperatures mimicking a winter to summer transition. Toxicity was monitored by differential respiration, phospholipid fatty acid analysis, polymerase chain reaction-denaturing gradient gel electrophoresis and DNA sequencing. Notwithstanding the effect of Ag MPs, nanosilver had an obvious, additional impact on the microbial community, underscoring the importance of particle size in toxicity. This impact was evidenced by levels of differential respiration in 0.066% Ag NP-treated soil that were only half that of control soils, a decrease in signature bacterial fatty acids, and changes in both richness and evenness in bacterial and fungal DNA sequence assemblages. Prominent after Ag NP-treatment were Hypocreales fungi, which increased to 70%, from only 1% of fungal sequences under control conditions. Genera within this Order known for their antioxidant properties (Cordyceps/Isaria) dominated the fungal assemblage after NP addition. In contrast, sequences attributed to the nitrogen-fixing Rhizobiales bacteria appeared vulnerable to Ag NP-mediated toxicity. This combination of physiological, biochemical and molecular studies clearly demonstrate that Ag NPs can severely disrupt the natural seasonal progression of tundra assemblages.

Cerium oxide nanoparticles have found numerous applications in the biomedical industry due to their strong antioxidant properties. In the current study, we report the influence of nine different physical and chemical parameters: pH, aeration and, concentrations of MgSO(4), CaCl(2), KCl, natural organic matter, fructose, nanoparticles and Escherichia coli, on the antibacterial activity of dextran coated cerium oxide nanoparticles. A least-squares quadratic regression model was developed to understand the collective influence of the tested parameters on the anti-bacterial activity and subsequently a computer-based, interactive visualization tool was developed. The visualization allows us to elucidate the effect of each of the parameters in combination with other parameters, on the antibacterial activity of nanoparticles. The results indicate that the toxicity of CeO(2) NPs depend on the physical and chemical environment; and in a majority of the possible combinations of the nine parameters, non-lethal to the bacteria. In fact, the cerium oxide nanoparticles can decrease the anti-bacterial activity exerted by magnesium and potassium salts.

It is not known if the annual production of tonnes of industrial nanoparticles (NPs) has the potential to impact terrestrial microbial communities, which are so necessary for ecosystem functioning. Here, we have examined the consequences of adding zero valent copper and zinc oxide NPs to soil in pots that were then maintained under field conditions. The fate of these NPs, as well as changes in the microbial communities, was monitored over 162 days. Both NP types traveled through the soil matrix, albeit at differential rates, with Cu NPs retained in the soil matrix at a higher rate compared to ZnO NPs. Leaching of Cu and Zn ions from the parent NPs was also observed as a function of time. Analysis of microbial communities using culture-dependent and independent methods clearly indicated that Cu and ZnO NPs altered the microbial community structure. In particular, two orders of organisms found in rhizosphere, Flavobacteriales and Sphingomonadales, appeared to be particularly susceptible to the presence of NPs. Together, the migration of NPs through soil matrix and the ability of these potential pollutants to influence the composition of microbial community in this field study, cannot help but raise some environmental concerns.

Of the few preserved areas in the northeast of United States, the soil in the Pine Barrens Forests presents a harsh environment for the microorganisms to grow and survive. In the current study we report the use of clustering methods to scientifically select the sampling locations that would represent the entire forest and also report the microbial diversity present in various horizons of the soil. Sixty six sampling locations were selected across the forest and soils were collected from three horizons (sampling depths). The three horizons were 0-10 cm (Horizon O); 11-25 cm (Horizon A) and 26-40 cm (Horizon B). Based on the total microbial substrate utilization pattern and K-means clustering analysis, the soil in the Pine Barrens Forest can be classified into four distinct clusters at each of the three horizons. One soil sample from each of the four clusters were selected and archaeal and bacterial populations within the soil studied using pyrosequencing method. The results show the microbial communities present in each of these clusters are different. Within the microbial communities present, microorganisms involved in nitrogen cycle occupy a major fraction of microbial community in the soil. High level of diversity was observed for nitrogen fixing bacteria. In contrast, Nitrosovibrio and Nitrosocaldus spp are the single bacterial and archaeal population respectively carrying out ammonia oxidation in the soil.

Although prior studies have demonstrated a smoking-induced field of molecular injury throughout the lung and airway, the impact of smoking on the airway epithelial proteome and its relationship to smoking-related changes in the airway transcriptome are unclear.Airway epithelial cells were obtained from never (n = 5) and current (n = 5) smokers by brushing the mainstem bronchus. Proteins were separated by one dimensional polyacrylamide gel electrophoresis (1D-PAGE). After in-gel digestion, tryptic peptides were processed via liquid chromatography/ tandem mass spectrometry (LC-MS/MS) and proteins identified. RNA from the same samples was hybridized to HG-U133A microarrays. Protein detection was compared to RNA expression in the current study and a previously published airway dataset. The functional properties of many of the 197 proteins detected in a majority of never smokers were similar to those observed in the never smoker airway transcriptome. LC-MS/MS identified 23 proteins that differed between never and current smokers. Western blotting confirmed the smoking-related changes of PLUNC, P4HB1, and uteroglobin protein levels. Many of the proteins differentially detected between never and current smokers were also altered at the level of gene expression in this cohort and the prior airway transcriptome study. There was a strong association between protein detection and expression of its corresponding transcript within the same sample, with 86% of the proteins detected by LC-MS/MS having a detectable corresponding probeset by microarray in the same sample. Forty-one proteins identified by LC-MS/MS lacked detectable expression of a corresponding transcript and were detected in

Our understanding of how engineered nanoparticles (NPs) migrate through soil and affect microbial communities is scarce. In the current study we examined how metal NPs, including those from the iron triad (iron, cobalt and nickel), moved through pots of soil maintained under winter field conditions for 50 days, when mesophilic bacteria may not be dividing. Based on total metal analysis, cobalt and nickel were localized in the top layer of soil, even after exposure to high precipitation and freeze–thaw cycles. In contrast, a bimodal distribution of silver was observed. Due to high endogenous levels of iron, the migration pattern of these NPs could not be determined. Pyrosequence analysis of the bacterial communities revealed that there was no significant engineered NP-mediated decline in microbial richness. However, analysis of individual genera showed that Sphingomonas and Lysobacter were represented by fewer sequences in horizons containing elevated metal levels whereas there was an increase in the numbers of Flavobacterium and Niastella . Collectively, the results indicate that along with the differential migration behavior of NPs in the soil matrix, their impact on soil bacterial diversity appears to be dependent on environmental parameters.