Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth.

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multimodal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared with term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.

A Case Report on the Effectiveness of Virtual Monitoring of Postdischarge COVID-19 Positive Patients in a Rural Hospital Setting: A Retrospective Review.

Objective: The pandemic has pushed hospital system to re-evaluate the ways they provide care. West Tennessee Healthcare (WTH) developed a remote patient monitoring (RPM) program to monitor positive COVID-19 patients after being discharged from the hospital for any worsening symptomatology and preemptively mitigate the potential of readmission. Methods: We sought to compare the readmission rates of individuals placed on our remote monitoring protocol with individuals not included in the program. We selected remotely monitored individuals discharged from WTH from October 2020 to December 2020 and compared these data points with a control group. Results: We analyzed 1,351 patients with 241 patients receiving no RPM intervention, 969 patients receiving standard monitoring, and 141 patients enrolled in our 24-h remote monitoring. Our lowest all cause readmission rate was 4.96% (p = 0.37) in our 24-h remote monitoring group. We also collected 641 surveys from the monitored patients with two statistically significant answers. Discussion: The low readmission rate noted in our 24-h remotely monitored cohort signifies a potential opportunity that a program of this nature can create for a health care system struggling during a resource-limited time to continue to provide quality care. Conclusion: The program allowed the allocation of hospital resources for individuals with more acute states and monitored less critical patients without using personal protective equipment. The novel program was able to offer an avenue to improve resource utilization and provide care for a health system in a rural area. Further investigation is needed; however, significant opportunities can be seen with data obtained during the study.

A target-cell limited model can reproduce influenza infection dynamics in hosts with differing immune responses.

We consider a hierarchy of ordinary differential equation models that describe the within-host viral kinetics of influenza infections: the IR model explicitly accounts for an immune response to the virus, while the simpler, target-cell limited TEIV and TV models do not. We show that when the IR model is fitted to pooled experimental murine data of the viral load, fraction of dead cells, and immune response levels, its parameters values can be determined. However, if, as is common, only viral load data are available, we can estimate parameters of the TEIV and TV models but not the IR model. These results are substantiated by a structural and practical identifiability analysis. We then use the IR model to generate synthetic data representing infections in hosts whose immune responses differ. We fit the TV model to these synthetic datasets and show that it can reproduce the characteristic exponential increase and decay of viral load generated by the IR model. Furthermore, the values of the fitted parameters of the TV model can be mapped from the immune response parameters in the IR model. We conclude that, if only viral load data are available, a simple target-cell limited model can reproduce influenza infection dynamics and distinguish between hosts with differing immune responses.

Notes on fiber length measurements: A case study in the underbelly of open source neuroscience.

Being on the bleeding edge of research requires the use of new and regularly updated software. The result is the occasional and inevitable occurrence of bugs. In the following work we present a case study where a feature request introduced a bug in a neuroimaging software package, which had consequences for the quality of results in a published article. We discuss the process of diagnosis, rectification and analysis replication.

Children's exposure to environmental lead: A review of potential sources, blood levels, and methods used to reduce exposure.

Lead has been used for thousands of years in different anthropogenic activities thanks to its unique properties that allow for many applications such as the manufacturing of drinking water pipes and its use as additives to gasoline and paint. However, knowledge of the adverse impacts of lead on human health has led to its banning from several of its applications, with the main goal of reducing environmental pollution and protecting human health. Human exposure to lead has been linked to different sources of contamination, resulting in high blood lead levels (BLLs) and adverse health implications, primarily in exposed children. Here, we present a summary of a literature review on potential lead sources affecting blood levels and on the different approaches used to reduce human exposure. The findings show a combination of different research approaches, which include the use of inspectors to identify problematic areas in homes, collection and analysis of environmental samples, different lead detection methods (e.g. smart phone applications to identify the presence of lead and mass spectrometry techniques). Although not always the most effective way to predict BLLs in children, linear and non-linear regression models have been used to link BLLs and environmental lead. However, multiple regressions and complex modelling systems would be ideal, especially when seeking results in support of decision-making processes. Overall, lead remains a pollutant of concern and many children are still exposed to it through environmental and drinking water sources. To reduce exposure to lead through source apportionment methods, recent technological advances using high-precision lead stable isotope ratios measured on multi-collector induced coupled plasma mass spectrometry (MC-ICP-MS) instruments have created a new direction for identifying and then eliminating prevalent lead sources associated with high BLLs.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

The Graded Change in Connectivity across the Ventromedial Prefrontal Cortex Reveals Distinct Subregions.

The functional heterogeneity of the ventromedial prefrontal cortex (vmPFC) suggests it may include distinct functional subregions. To date these have not been well elucidated. Regions with differentiable connectivity (and as a result likely dissociable functions) may be identified using emergent data-driven approaches. However, prior parcellations of the vmPFC have only considered hard splits between distinct regions, although both hard and graded connectivity changes may exist. Here we determine the full pattern of change in structural and functional connectivity across the vmPFC for the first time and extract core distinct regions. Both structural and functional connectivity varied along a dorsomedial to ventrolateral axis from relatively dorsal medial wall regions to relatively lateral basal orbitofrontal cortex. The pattern of connectivity shifted from default mode network to sensorimotor and multimodal semantic connections. This finding extends the classical distinction between primate medial and orbital regions by demonstrating a similar gradient in humans for the first time. Additionally, core distinct regions in the medial wall and orbitofrontal cortex were identified that may show greater correspondence to functional differences than prior hard parcellations. The possible functional roles of the orbitofrontal cortex and medial wall are discussed.

The Association of Broadband Internet Access and Telemedicine Utilization in rural Western Tennessee: an observational study.

BACKGROUND: Broadband access has been highlighted as a national policy priority to improve access to care in rural communities. OBJECTIVE: To determine whether broadband internet availability was associated with telemedicine adoption among a rural patient population in western Tennessee. METHODS: Observational study using electronic medical record data from March 13th, 2019 to March 13th, 2021. Multivariable logistic regression incorporating individual-level characteristics with broadband availability, income, educational attainment, and primary care physician supply at the zip code level, and rural status as determined at the county level. SETTING: Single health system in western Tennessee. PARTICIPANTS: Adult patients with one or more in-person or remote encounter in a health system in western Tennessee and residing in western Tennessee between March 13th, 2019 and March 13th, 2021 (N = 54,688). OUTCOME MEASURES: Completion of one or more video encounters in the year following March 13th, 2020 (N = 3199; 7%). Our primary characteristic of interest was the proportion of residents in each zip code with access to the internet meeting the Federal Communications Commission definition of broadband access, adjusting for age, gender, race, income, educational attainment, insurance type, rural status, and primary care provider supply. RESULTS: Patients in a rural western Tennessee health system were predominantly white (79%), residing in rural zip codes (73%) with median household incomes ($52,085) less than state and national averages. Patients residing in a zip code where there is 80 to 100% broadband access compared to 0 to 20% were more likely in the year following March 13th, 2020 to have completed both telemedicine and in-person visits ([OR; 95% CI] 1.57; 1.29, 1.94), completed only telemedicine visits (2.26; 1.71, 2.97), less likely to have only completed in-person visits (0.81; 0.74, 0.89), but no more or less likely to have accessed no care (1.07; 0.97, 1.18). DISCUSSION: The availability of broadband internet was shown to be one of many factors associated with the utilization of telemedicine for a rural, working-class community after March 13th, 2020. CONCLUSIONS: Access to broadband internet is a determinant of access to telemedicine for patients in rural communities and should be a priority for policymakers interested in improving health and access to care for rural patients.

A tutorial and tool for exploring feature similarity gradients with MRI data.

There has been an increasing interest in examining organisational principles of the cerebral cortex (and subcortical regions) using different MRI features such as structural or functional connectivity. Despite the widespread interest, introductory tutorials on the underlying technique targeted for the novice neuroimager are sparse in the literature. Articles that investigate various "neural gradients" (for example based on region studied "cortical gradients," "cerebellar gradients," "hippocampal gradients" etc … or feature of interest "functional gradients," "cytoarchitectural gradients," "myeloarchitectural gradients" etc …) have increased in popularity. Thus, we believe that it is opportune to discuss what is generally meant by "gradient analysis". We introduce basics concepts in graph theory, such as graphs themselves, the degree matrix, and the adjacency matrix. We discuss how one can think about gradients of feature similarity (the similarity between timeseries in fMRI, or streamline in tractography) using graph theory and we extend this to explore such gradients across the whole MRI scale; from the voxel level to the whole brain level. We proceed to introduce a measure for quantifying the level of similarity in regions of interest. We propose the term "the Vogt-Bailey index" for such quantification to pay homage to our history as a brain mapping community. We run through the techniques on sample datasets including a brain MRI as an example of the application of the techniques on real data and we provide several appendices that expand upon details. To maximise intuition, the appendices contain a didactic example describing how one could use these techniques to solve a particularly pernicious problem that one may encounter at a wedding. Accompanying the article is a tool, available in both MATLAB and Python, that enables readers to perform the analysis described in this article on their own data. We refer readers to the graphical abstract as an overview of the analysis pipeline presented in this work.

Fabrication of spectrally sharp Si-based dielectric resonators: combining etaloning with Mie resonances.

We use low-resolution optical lithography joined with solid state dewetting of crystalline, ultra-thin silicon on insulator (c-UT-SOI) to form monocrystalline, atomically smooth, silicon-based Mie resonators in well-controlled large periodic arrays. The dewetted islands have a typical size in the 100 nm range, about one order of magnitude smaller than the etching resolution. Exploiting a 2 µm thick SiO2 layer separating the islands and the underlying bulk silicon wafer, we combine the resonant modes of the antennas with the etalon effect. This approach sets the resonance spectral position and improves the structural colorization and the contrast between scattering maxima and minima of individual resonant antennas. Our results demonstrate that templated dewetting enables the formation of defect-free, faceted islands that are much smaller than the nominal etching resolution and that an appropriate engineering of the substrate improves their scattering properties. These results are relevant to applications in spectral filtering, structural color and beam steering with all-dielectric photonic devices.

1,2-cis-Selective glucosylation enabled by halogenated benzyl protecting groups.

We report on our initial results from a systematic effort to implement electron-withdrawing protecting groups and Lewis basic solvents/additives as an approach to 1,2-cis(α)-selective O-glucosylation. 1,2-cis-Selective O-glucosylations are reported with thioglucosides and glucosyl trichloroacetimidates and a range of acceptors. A correlation between electron-withdrawing effects and 1,2-cis selectivity has been established. This phenomenon may prove to be broadly applicable in the area of chemical O-glycosylation.

Evaluating a sensitive issue: reliability of a clinical evaluation for allodynia severity.

Purpose/Aim: Allodynia is a common feature of neuropathic pain with few validated clinical evaluation options. We identified a need to estimate the measurement properties of the standardised evaluation procedure for static mechanical allodynia severity popularised by the somatosensory rehabilitation of pain method, known as the rainbow pain scale. This study (www.clinicaltrials.gov. NCT02070367) undertook preliminary investigation of the inter-rater and test-retest reliability of the rainbow pain scale.Methods: Persons with pain in one upper extremity after Complex Regional Pain Syndrome, a peripheral nerve injury or a recent hand fracture were recruited for assessment of static mechanical allodynia threshold using calibrated monofilaments by two raters at baseline, and repeated assessment one week later.Results: Single measures estimates suggested inter-rater reliability was substantial for the rainbow pain scale [intra-class correlation coefficient = 0.78 (n = 31), p < 0.001]. Test-retest reliability was also excellent at with an intraclass correlation coefficient of 0.87 [n = 28, p < 0.001]. However, confidence intervals suggest the true values could be more moderate, with lower bounds of the 95% confidence interval at 0.60 and 0.74, respectively.Conclusions: This pilot study has generated preliminary support for the inter-rater and test-retest reliability of the rainbow pain scale. Future studies should seek to increase confidence in estimates of reliability, and estimate validity and responsiveness to change in persons with somatosensory disorders.

Allodynography: Reliability of a New Procedure for Objective Clinical Examination of Static Mechanical Allodynia.

OBJECTIVE: There is a need for reliable and valid clinical assessment tools for quantifying allodynia in neuropathic pain. Allodynography has been proposed as a useful standardized procedure for clinical assessment of mechanical allodynia. This study (www.clinicaltrials.gov NCT02070367) undertook preliminary investigation of the measurement properties of allodynography, a new standardized clinical examination procedure for mapping the area of cutaneous allodynia. METHODS: Persons with pain in one upper extremity after complex regional pain syndrome, a peripheral nerve injury, or who had recently experienced a hand fracture were recruited for assessment of static mechanical allodynia (based on perception of a 15g force stimulus delivered by Semmes-Weinstein monofilament #5.18 as painful) by two raters at baseline; the assessment was repeated one week later. RESULTS: Single-measures estimates suggested inter-rater reliability for allodynography was excellent at an intraclass correlation coefficient (ICC) of 0.97 (N = 12); test-retest reliability was also excellent at ICC = 0.89 (N = 10) for allodynography (P < 0.001 for both). Confidence intervals' lower bounds confirm inter-rater reliability as excellent (0.90) but were less definitive for test-retest (0.59). CONCLUSIONS: This preliminary study supports the inter-rater and test-retest reliability of allodynography. Studies on larger samples in multiple contexts and reporting other measurement properties are warranted.

Predicting glycosaminoglycan surface protein interactions and implications for studying axonal growth.

Cell-surface carbohydrates play important roles in numerous biological processes through their interactions with various protein-binding partners. These interactions are made possible by the vast structural diversity of carbohydrates and the diverse array of carbohydrate presentations on the cell surface. Among the most complex and important carbohydrates are glycosaminoglycans (GAGs), which display varied stereochemistry, chain lengths, and patterns of sulfation. GAG-protein interactions participate in neuronal development, angiogenesis, spinal cord injury, viral invasion, and immune response. Unfortunately, little structural information is available for these complexes; indeed, for the highly sulfated chondroitin sulfate motifs, CS-E and CS-D, there are no structural data. We describe here the development and validation of the GAG-Dock computational method to predict accurately the binding poses of protein-bound GAGs. We validate that GAG-Dock reproduces accurately (<1-Å rmsd) the crystal structure poses for four known heparin-protein structures. Further, we predict the pose of heparin and chondroitin sulfate derivatives bound to the axon guidance proteins, protein tyrosine phosphatase σ (RPTPσ), and Nogo receptors 1-3 (NgR1-3). Such predictions should be useful in understanding and interpreting the role of GAGs in neural development and axonal regeneration after CNS injury.

Fiber length profiling: A novel approach to structural brain organization.

There has been a recent increased interest in the structural connectivity of the cortex. However, an important feature of connectivity remains relatively unexplored; tract length. In this article, we develop an approach to characterize fiber length distributions across the human cerebral cortex. We used data from 76 participants of the Adult WU-Minn Human Connectome Project using probabilistic tractography. We found that connections of different lengths are not evenly distributed across the cortex. They form patterns where certain areas have a high density of fibers of a specific length while other areas have very low density. To assess the relevance of these new maps in relation to established characteristics, we compared them to structural indices such as cortical myelin content and cortical thickness. Additionally, we assessed their relation to resting state network organization. We noted that areas with very short fibers have relatively more myelin and lower cortical thickness while the pattern is inverted for longer fibers. Furthermore, the cortical fiber length distributions produce specific correlation patterns with functional resting state networks. Specifically, we find evidence that as resting state networks increase in complexity, their length profiles change. The functionally more complex networks correlate with maps of varying lengths while primary networks have more restricted correlations. We posit that these maps are a novel way of differentiating between 'local modules' that have restricted connections to 'neighboring' areas and 'functional integrators' that have more far reaching connectivity.

Material- and Site-Specific Partition Coefficients for Beneficial Use Assessments.

Partition coefficient (Kd) values available in the literature are often used in fate and transport modeling conducted as part of beneficial use risk assessments for industrial byproducts. Because element partitioning depends on soil properties as well as characteristics of the byproduct leachate, site-specific Kd values may lead to more accurate risk assessment. In this study, contamination risk to groundwater of beneficially reused byproducts was assessed using batch leaching tests on waste to energy bottom ash and coal combustion fly ash. Leachates were equilibrated with eight different soils to obtain the waste-soil-specific Kd,exp values for the metals of interest. The Kd,exp values were used as inputs in the Industrial Waste Management Evaluation Model to demonstrate the degree to which Kd estimates affect risk assessment outcomes. Measured Kd,exp values for the most part fell within the large range of Kd values reported in the literature, but IWEM results using default Kd values for some types of soils resulted in overestimated risk compared to those derived from Kd,exp values. Modeled concentration at the receptor location was much lower for some elements for those soils with high concentrations of iron and aluminum.

Corneal Endothelial Blebs Induced in Scleral Lens Wearers.

SIGNIFICANCE: In the bleb phenomenon, some endothelial cells transiently lose their specular reflection. This has been reported during contact lens wear and goggle-induced hypoxia or hypercapnia. PURPOSE: The purposes of this study were to determine whether blebs appear after scleral lens wear and if their appearance is influenced by lens clearance and to compare bleb and cell sizes. METHODS: Twenty-one subjects were fitted with two similar scleral lenses with different targeted clearances of 200 and 400 µm (the SL200 and SL400, respectively). Each lens was worn unilaterally for 25 minutes, whereas the other eye served as a control. Before and after lens wear, the endothelium was photographed using specular microscopy. The number of blebs and measurements of the areas of cells and blebs were analyzed. Paired t tests compared differences in the areas of cells and blebs. Differences in median bleb number were evaluated using the Wilcoxon test. RESULTS: After wearing the SL200 and SL400 lenses, respectively, 9 and 14 subjects had at least one bleb. The median bleb number after wearing lenses was significantly different (SL200, 0.00; SL400, 1.00; P = .02). Bleb and cell areas were significantly different (blebs, 293 ± 28; cells, 370 ± 32 µm; P < .0001). CONCLUSIONS: After 25 minutes of wearing scleral lenses with each of the two targeted clearances, SL400 induced significantly more blebs than did SL200, suggesting evidence of reduced oxygen and/or increased carbon dioxide levels under scleral lenses fitted with excessive clearance. Blebs may occur more in smaller cells.

An emergent functional parcellation of the temporal cortex.

The temporal lobe has been associated with various cognitive functions which include memory, auditory cognition and semantics. However, at a higher level of conceptualisation, all of the functions associated with the temporal lobe can be considered as lying along one major axis; from modality-specific to modality-general processing. This paper used a spectral reordering technique on resting-state and task-based functional data to extract the major organisational axis of the temporal lobe in a bottom-up, data-driven fashion. Independent parcellations were performed on resting-state scans from 71 participants and active semantic task scans from 23 participants acquired using dual echo gradient echo planar imaging in order to preserve signal in inferior temporal cortex. The resulting organisational axis was consistent (over dataset and hemisphere) and progressed from superior temporal gyrus and posterior inferior temporal cortex to ventrolateral anterior temporal cortex. A hard parcellation separated a posterior (superior temporal and posterior fusiform and inferior temporal gyri) and an anterior cluster (ventrolateral anterior temporal lobe). The functional connectivity of the hard clusters supported the hypothesis that the connectivity gradient separated modality-specific and modality-general regions. This hypothesis was then directly tested by performing a VOI analysis upon an independent semantic task-based data set including auditory and visually presented stimuli. This confirmed that the ventrolateral anterior aspects of the temporal lobe are associated with modality-general processes whilst posterior and superior aspects are specific to certain modalities, with the posterior inferior subregions involved in visual processes and superior regions involved in audition.

The presence of a feeder layer improves human corneal endothelial cell proliferation by altering the expression of the transcription factors Sp1 and NFI.

Based on the use of tissue-cultured human corneal endothelial cells (HCECs), cell therapy is a very promising avenue in the treatment of corneal endothelial pathologies such as Fuchs' dystrophy, and post-surgical corneal edema. However, once in culture, HCECs rapidly lose their phenotypic and physiological characteristics, and are therefore unsuitable for the reconstruction of a functional endothelial monolayer. Expression of NFI, a transcription factor that can either function as an activator or a repressor of gene transcription, has never been examined in endothelial cells. The present study therefore aimed to determine the impact of a non-proliferating, lethally irradiated i3T3 feeder layer on the maintenance of HCEC's morphological characteristics, and both the expression and stability of Sp1 (a strong transcriptional activator) and NFI in such cells. The typical morphology of endothelial cells was best maintained when 8 × 103/cm2 HCECs were co-cultured in the presence of 2 × 104 cells/cm2 i3T3. HCECs were found to express both Sp1 and NFI in vitro. Also, the presence of i3T3 led to higher levels of Sp1 and NFI in HCECs, with a concomitant increase in their DNA binding levels (assessed by electrophoretic mobility shift assays (EMSA)). Specifically, i3T3 increased the expression of the NFIA, NFIB and NFIC isoforms, without a noticeable increase in their mRNAs (as revealed by gene profiling on microarray). Gene profiling analysis also identified a few feeder layer-dependent, differentially regulated genes whose protein products may contribute to improving the properties of HCECs in culture. Therefore, co-culturing HCECs with an i3T3 feeder layer clearly improves their morphological characteristics by maintaining stable levels of Sp1 and NFI in cell culture.