Virtual colorimetric sensor array: single ionic liquid for solvent discrimination.

There is a continuing need to develop high-performance sensors for monitoring organic solvents, primarily due to the environmental impact of such compounds. In this regard, colorimetric sensors have been a subject of intense research for such applications. Herein, we report a unique virtual colorimetric sensor array based on a single ionic liquid (IL) for accurate detection and identification of similar organic solvents and mixtures of such solvents. In this study, we employ eight alcohols and seven binary mixtures of ethanol and methanol as analytes to provide a stringent test for assessing the capabilities of this array. The UV-visible spectra of alcoholic solutions of the IL used in this study show two absorption bands. Interestingly, the ratio of absorbance for these two bands is found to be extremely sensitive to alcohol polarity. A virtual sensor array is created by using four different concentrations of IL sensor, which allowed identification of these analytes with 96.4-100% accuracy. Overall, this virtual sensor array is found to be very promising for discrimination of closely related organic solvents.

GUMBOS matrices of variable hydrophobicity for matrix-assisted laser desorption/ionization mass spectrometry.

RATIONALE: Detection of hydrophobic peptides remains a major obstacle for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). This stems from the fact that most matrices for MALDI are hydrophilic and therefore have low affinities for hydrophobic peptides. Herein, 1-aminopyrene (AP) and AP-derived group of uniform materials based on organic salts (GUMBOS) as novel matrices for MALDI-MS analyses of peptides were investigated for hydrophobic and hydrophilic peptides. METHODS: A number of solid-phase AP-based GUMBOS are synthesized with variable hydrophobicity simply by changing the counterions. Structures were confirmed by use of (1)H NMR and electrospray ionization mass spectrometry (ESI-MS). 1-Octanol/water partition coefficients (Ko/w) were used to measure the hydrophobicity of the matrices. A dried-droplet method was used for sample preparation. All spectra were obtained using a MALDI-TOF mass spectrometer in positive ion reflectron mode. RESULTS: A series of AP-based GUMBOS was synthesized including [AP][chloride] ([AP][Cl]), [AP][ascorbate] ([AP][Asc]) and [AP][bis(trifluoromethane)sulfonimide] ([AP][NTf2]). The relative hydrophobicities of these compounds and α-cyano-4-hydroxycinnamic acid (CHCA, a common MALDI matrix) indicated that AP-based GUMBOS can be tuned to be much more hydrophobic than CHCA. A clear trend is observed between the signal intensities of hydrophobic peptides and hydrophobicity of the matrix. CONCLUSIONS: MALDI matrices of GUMBOS with tunable hydrophobicities are easily obtained simply by varying the counterion. We have found that hydrophobic matrix materials are very effective for MALDI determination of hydrophobic peptides and, similarly, the more hydrophilic peptides displayed greater intensity in the more hydrophilic matrix.

Modeling the spread of COVID-19 in spatio-temporal context.

This study aims to use data provided by the Virginia Department of Public Health to illustrate the changes in trends of the total cases in COVID-19 since they were first recorded in the state. Each of the 93 counties in the state has its COVID-19 dashboard to help inform decision makers and the public of spatial and temporal counts of total cases. Our analysis shows the differences in the relative spread between the counties and compares the evolution in time using Bayesian conditional autoregressive framework. The models are built under the Markov Chain Monte Carlo method and Moran spatial correlations. In addition, Moran's time series modeling techniques were applied to understand the incidence rates. The findings discussed may serve as a template for other studies of similar nature.

Outcomes of Guided Personalized Surgery (GPS)-Navigated Reverse Polarity Total Shoulder Joint Replacement in a Low-Volume Hospital.

Introduction Reverse polarity shoulder arthroplasty (RSA) is an evolving surgery, and its indications have expanded over time. Apart from cuff tear arthropathy (CTA), it is recommended for complex proximal humerus fractures in the elderly, inflammatory arthritis, primary osteoarthritis in the elderly, and revision for failed hemiarthroplasty. Glenoid base plate placement and fixation are important to prevent complications, especially glenoid base plate loosening, dislocation, and scapular notching, and to improve longevity. Guided personalized surgery (GPS)-navigated RSA was devised to optimize the glenoid base plate position and fixation. Methodology A retrospective study was carried out in a low-volume district general hospital in England. All the patients who underwent GPS-navigated RSA were included. Their preoperative glenoid version, bone stock, glenoid base plate, and glenoid screw lengths were analysed. Preoperative and post-surgery patient-reported outcomes were gathered using the Oxford Shoulder Score (OSS) at six months and annually thereafter. Results Fourteen patients have undergone GPS-navigated RSA in our institute since 2018. Ten patients were female. All of them had a retroverted glenoid with a mean value of 13.6 degrees. Ten out of 14 patients had an augmented glenoid base plate. This included six eight-degree posterior augmentations, three 10-degree superior augmentations, and one extended cage peg. The follow-up period was six months to five years, depending on the date of surgery, and none of the patients dropped out of follow-up. The OSS revealed statistically significant improvement from preoperative values to six months postoperative, an improvement of 21.64±7.175. It also showed progressive improvement over time during postoperative follow-up, and the three-year mean was 47. The commonest complication was fractures, which happened in four cases. There were no infections or dislocations. Discussion Guided personalized surgery-navigated RSA was performed on selected patients at our institution when they were not suitable for conventional RSA due to distorted glenoid anatomy. Glenoid base plate positioning and fixation are important to optimize the outcome of RSA. Guided personalized surgery navigation is helpful in achieving optimum glenoid base placement, especially when the normal glenoid anatomy is distorted. There were no dislocations, glenoid base plate loosening, or scapular notching in the study group. There were four reported fractures, which was comparable with the published literature.

Multimodal quantitative magnetic resonance imaging of thalamic development and aging across the human lifespan: implications to neurodegeneration in multiple sclerosis.

The human brain thalami play essential roles in integrating cognitive, sensory, and motor functions. In multiple sclerosis (MS), quantitative magnetic resonance imaging (qMRI) measurements of the thalami provide important biomarkers of disease progression, but late development and aging confound the interpretation of data collected from patients over a wide age range. Thalamic tissue volume loss due to natural aging and its interplay with lesion-driven pathology has not been investigated previously. In this work, we used standardized thalamic volumetry combined with diffusion tensor imaging, T2 relaxometry, and lesion mapping on large cohorts of controls (N = 255, age range = 6.2-69.1 years) and MS patients (N = 109, age range = 20.8-68.5 years) to demonstrate early age- and lesion-independent thalamic neurodegeneration.

Human brain iron mapping using atlas-based T2 relaxometry.

Several in vivo quantitative MRI techniques have been proposed as surrogate measures to map iron content in the human brain. The majority of in vivo quantitative MRI iron mapping methods used the age-dependent iron content data based on postmortem data. In this work, we fused atlas-based human brain volumetry obtained on a large cohort of healthy adults using FreeSurfer with T(2) relaxation time measurements. We provide a brain atlas-based T(2) relaxation time map, which was subsequently used along with published postmortem iron content data to obtain a map of iron content in subcortical and cortical gray matter. We have also investigated the sensitivity of the linear model relating transverse relaxation rate with published iron content to the number of regions used. Our work highlights the challenges encountered on using the simple model along with postmortem data to infer iron content in several brain regions where postmortem iron data are scant (e.g., corpus callosum, amygdale).

Diffusion tensor quantification and cognitive correlates of the macrostructure and microstructure of the corpus callosum in typically developing and dyslexic children.

Noninvasive quantitative MRI methods, such as diffusion tensor imaging (DTI), can offer insights into the structure-function relationships in human developmental brain disorders. In this article, we quantified the macrostructural and microstructural attributes of the corpus callosum (CC) in children with dyslexia and in typically developing readers of comparable age and gender. Diffusion anisotropy, and mean, radial and axial diffusivities of cross-sectional CC subregions were computed using a validated DTI methodology. The normalized posterior CC area was enlarged in children with dyslexia relative to that in typically developing children. Moreover, the callosal microstructural attributes, such as the mean diffusivity of the posterior middle sector of the CC, correlated significantly with measures of word reading and reading comprehension. Reading group differences in fractional anisotropy, mean diffusivity and radial diffusivity were observed in the posterior CC (CC5). This study demonstrates the utility of regional DTI measurements of the CC in understanding the neurobiology of reading disorders.

Multi-modal quantitative MRI investigation of brain tissue neurodegeneration in multiple sclerosis.

PURPOSE: To investigate the utility of multimodal quantitative MRI (qMRI) and atlas-based methods to identify characteristics of lesion-driven injury and neurodegeneration in relapsing remitting multiple sclerosis (RRMS). MATERIALS AND METHODS: This work is health insurance portability and accountability act compliant. High resolution T1-weighted, dual echo, and fluid-attenuated inversion recovery and diffusion tensor MRI images were prospectively acquired on 68 RRMS patients (range, 25-58 years) and 68 age-matched controls. The data were analyzed using standardized human brain atlas-based tissue segmentation procedures to obtain regional volumes and their corresponding T2 relaxation times and DTI maps. RESULTS: Group-averaged brain atlas-based qMRI maps of T2, fractional anisotropy and diffusivities are visually presented and compared between controls and RRMS. The analysis shows a widespread injury in RRMS. Atrophy of the corpus callosum (CC) was substantial in RRMS. The qMRI attributes of the neocortex in combination with the CC such as T2 and diffusivities were elevated and correlated with disability. CONCLUSION: Using a standardized multimodal qMRI acquisition and analyses that accounted for lesion distribution we demonstrate that cerebral pathology is widespread in RRMS. Our analysis of CC and neocortex qMRI metrics in relation to disability points to a neurodegenerative injury component that is independent from lesions.

Atlas-based investigation of human brain tissue microstructural spatial heterogeneity and interplay between transverse relaxation time and radial diffusivity.

Microstructural metrics obtained using magnetic resonance imaging (MRI) such as transverse relaxation time and radial diffusivity have been used as in vivo markers of human brain tissue integrity. Considering the sensitivity of these parameters to some common biophysical contributors and their structural and spatial heterogeneity, we hypothesized that strong inter and intra-regional associations exist between these variables providing evidence to possible interplay between transverse relaxation time and radial diffusivity. To validate our hypothesis we obtained high resolution anatomical T1-weighted data and fused it with T2-relaxometry and diffusion tensor imaging (DTI) data on a cohort of healthy adults. The anatomical data were parcellated using FreeSurfer and then coaligned and fused with the T2 and DTI maps. Our data reveal some association between transverse relaxation and radial diffusivity that may help toward the interpretation and modeling of the biophysical contributors to the measured MRI metrics.

Human brain atlas-based volumetry and relaxometry: application to healthy development and natural aging.

This work investigated the feasibility and utility of using T2-weighted or dual spin-echo data to provide volume and T2 relaxation time for regional and global gray and white matter using standardized brain templates and anatomically labeled atlases. A total of 130 healthy males and females (age range 15-59 years) were included. Dual echo magnetic resonance imaging data were acquired and analyzed using standardized International Consortium for Human Brain Mapping atlas-based tissue segmentation procedures implemented in the statistical parametric mapping toolbox to obtain the age trajectories of volume and corresponding T2 relaxation time in whole brain white and gray matter, in the caudate nucleus and in the anterior limb of internal capsule. Whole brain gray matter and caudate nucleus volumes linearly decreased with age while whole brain white matter and anterior limb internal capsule volume increased slowly with age bilaterally in males and females. The relation between T2 relaxation time and age of whole brain gray and white matter, and caudate nucleus and anterior limb internal capsule followed a quadratic U-curve. The T2 relaxation times of the human brain followed a U curve both globally and regionally in both white and gray matter.

Defining the fetal cardiac axis between 11 + 0 and 14 + 6 weeks of gestation: experience with 100 consecutive pregnancies.

OBJECTIVE: The purpose of this study was to establish normal fetal cardiac axis values during the first and early second trimesters of pregnancy. METHODS: This was a prospective observational cohort study in which the fetal cardiac axis was assessed during ultrasound examinations in 100 consecutive fetuses between 11 + 0 and 14 + 6 weeks of gestation. Transabdominal, and, when indicated, transvaginal, approaches were used. Intraobserver and interobserver reproducibility were calculated. RESULTS: The cardiac axis ranged from 34.5 to 56.8° (mean (SD) 47.6 ± 5.6°) in 94 fetuses with normal cardiac anatomy. The fetal cardiac axis tended to be significantly higher in fetuses at 11 + 0 to 11 + 6 weeks of gestation than in fetuses at 12 + 0 to 14 + 6 weeks of gestation. Congenital heart defects were found in six out of 100 fetuses, four of which had abnormal cardiac axis values at 11 + 0 to 14 + 6 weeks of gestation. CONCLUSION: Cardiac axis measurement is possible in the first and early second trimesters of pregnancy. The assessment of cardiac axis at an early gestational age may help to identify pregnancies at high risk for congenital heart defects. Copyright

Protein Discrimination Using a Fluorescence-Based Sensor Array of Thiacarbocyanine-GUMBOS.

Sensitive and selective detection of proteins from complex samples has gained substantial interest within the scientific community. Early and precise detection of key proteins plays an important role in potential clinical diagnosis, treatment of different diseases, and proteomic research. In the study reported here, six different compounds belonging to a group of uniform materials based on organic salts (GUMBOS) have been synthesized using three thiacarbocyanine (TC) dyes and employed as fluorescent sensors. Fluorescence properties of micro- and nanoaggregates of these TC-based GUMBOS formed in phosphate buffer solutions are studied in the absence and presence of seven proteins. Fluorescence response patterns of these TC-based GUMBOS were analyzed by linear discriminant analysis (LDA). The constructed LDA model allowed discrimination of these seven proteins at various concentrations with 100% accuracy. The sensing and discrimination abilities of these TC-based GUMBOS were further evaluated in mixtures of two major proteins, i.e., human serum albumin and hemoglobin. Fluorescence response patterns of these mixtures were analyzed by LDA. This model allowed discrimination of various mixtures with 100% accuracy. Moreover, spiked urine samples were prepared and the responses of these sensors were collected and analyzed by LDA. Remarkably, discrimination of these seven proteins was also achieved with 100% accuracy.

Optimization Models for Scheduling of Jobs.

This work is motivated by a particular scheduling problem that is faced by logistics centers that perform aircraft maintenance and modification. Here we concentrate on a single facility (hangar) which is equipped with several work stations (bays). Specifically, a number of jobs have already been scheduled for processing at the facility; the starting times, durations, and work station assignments for these jobs are assumed to be known. We are interested in how best to schedule a number of new jobs that the facility will be processing in the near future. We first develop a mixed integer quadratic programming model (MIQP) for this problem. Since the exact solution of this MIQP formulation is time consuming, we develop a heuristic procedure, based on existing bin packing techniques. This heuristic is further enhanced by application of certain local optimality conditions.

Tunable GUMBOS-based sensor array for label-free detection and discrimination of proteins.

There is increasing interest in developing new sensor strategies for accurate detection and identification of proteins, primarily due to their significance in various biological processes. In this regard, fluorometric sensors and sensor arrays have been widely explored as facile and inexpensive analytical tools. In this manuscript, we report a sensor array approach, based on a novel group of 6-(p-toluidino)-2-naphthalenesulfonate (TNS)-based organic salts for sensitive and label-free sensing of proteins. In this proof-of-concept study, three proteins (human serum albumin (HSA), α-antitrypsin and ß-lactoglobulin (ß-lac)) and binary mixtures of HSA and α-antitrypsin were used to evaluate the senor array performance. The fingerprint sensor-response patterns, dependent on proteins and protein mixtures at different concentrations, generated from the TNS-based sensors were employed to develop predictive models using principal component analysis (PCA) and linear discriminant analysis (LDA). Interestingly, there is excellent correlation between clustering patterns of PCA and different concentrations of proteins and protein mixtures, which was employed for discrimination of proteins and protein mixtures regardless of concentrations. Furthermore, identification accuracy of the proposed fluorescence-sensor technique, towards discrimination of various concentrations of proteins and protein mixtures, was calculated to be 100%. Overall, this sensor strategy is found to be a very promising tool for accurate discrimination of absolute and relative concentrations of proteins and protein mixtures.

A solitary fibrous tumor of the kidney.

A solitary fibrous tumor (SFT) is an uncommon spindle cell neoplasm that usually occurs in the pleura, but may occur in extrapleural sites. Its occurrence in the kidney is rare. We report a SFT, clinically thought to be a renal cell carcinoma arising in the kidney of a 68-year-old female. The tumor was well-circumscribed and composed of a mixture of spindle cells and dense collagenous bands. Immunohistochemical studies revealed reactivity for CD34, CD99, and Bcl-2 protein, with no staining for keratin or muscle markers, confirming the diagnosis. The immunohistochemical study was the key to diagnosis. Several younger members of her family had colorectal and lung cancers suggesting the possibility of a familial or genetic susceptibility.

Global cerebral and regional multimodal neuroimaging markers of the neurobiology of autism: development and cognition.

Quantitative magnetic resonance imaging (MRI) studies of the microstructure and macrostructure in children with autism report contradictory results due, in part, to the autistic population heterogeneity from factors such as variation in intellect and inadequately accounting for age-related changes in brain development. In this report, the authors compared global and regional volumetry, relaxometry, anisotropy, and diffusometry of gray and white matter in 10 autism spectrum disorder children relative to the age-related trajectories obtained from 38 typically developing controls while controlling for nonverbal intellect using a validated quantitative MRI method. The normalized hippocampus volume increased with age in both autistic and typically developing individuals with limbic structures larger in autistic patients. Hippocampus volume, but not diffusivity or relaxation time, was larger in autistic children. Hippocampus volume was inversely correlated with nonverbal intellect across control individuals. The pattern of hippocampal abnormalities suggests a disturbance in early brain development in autistic children independent of intellect.

Human brain atlas-based multimodal MRI analysis of volumetry, diffusimetry, relaxometry and lesion distribution in multiple sclerosis patients and healthy adult controls: implications for understanding the pathogenesis of multiple sclerosis and consolidation of quantitative MRI results in MS.

Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease. In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T(2) relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing-remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component.

A computational framework to quantify tissue microstructural integrity using conventional MRI macrostructural volumetry.

In this work, we present a framework to fuse and quantify tissue microstructural attributes (e.g. diffusion, functional, relaxation and perfusion MRI) using high spatial resolution T1-weighted volumetric measurements. The proposed computational procedures can be implemented by utilizing advanced, image segmentation, registration and diffusion tensor image processing software. Feasibility of the framework is also demonstrated using in-house developed software and freely available software such as FreeSurfer for regional tissue segmentation, Advanced Normalization Tools (ANTs) for registration and DTIStudio for fiber tracking and diffusion tensor data processing. We also demonstrate the application of these methods in the provision of quality control measures to assess the fidelity of tissue segmentation and multi-modal MRI registration.