Decentralised Global Service Discovery for the Internet of Things.

The Internet of Things (IoT) consists of millions of devices deployed over hundreds of thousands of different networks, providing an ever-expanding resource to improve our understanding of and interactions with the physical world. Global service discovery is key to realizing the opportunities of the IoT, spanning disparate networks and technologies to enable the sharing, discovery, and utilisation of services and data outside of the context in which they are deployed. In this paper, we present Decentralised Service Registries (DSRs), a novel trustworthy decentralised approach to global IoT service discovery and interaction, building on DSF-IoT to allow users to simply create and share public and private service registries, to register and query for relevant services, and to access both current and historical data published by the services they discover. In DSR, services are registered and discovered using signed objects that are cryptographically associated with the registry service, linked into a signature chain, and stored and queried for using a novel verifiable DHT overlay. In contrast to existing centralised and decentralised approaches, DSRs decouple registries from supporting infrastructure, provide privacy and multi-tenancy, and support the verification of registry entries and history, service information, and published data to mitigate risks of service impersonation or the alteration of data. This decentralised approach is demonstrated through the creation and use of a DSR to register and search for real-world IoT devices and their data as well as qualified using a scalable cluster-based testbench for the high-fidelity emulation of peer-to-peer applications. DSRs are evaluated against existing approaches, demonstrating the novelty and utility of DSR to address key IoT challenges and enable the sharing, discovery, and use of IoT services.

Parallel CSF and serum temporal profile assessment of axonal injury biomarkers NF-L and pNF-H: Associations with patient outcome in moderate-severe traumatic brain injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels, 2) to evaluate CSF and serum NF-L and pNF-H associations with each other, and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-to-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n=277 unique subjects) and CSF (n=95 unique subjects) daily for one week, and serum every two weeks for six months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n=99 unique subjects) and CSF (n=54 unique subjects) NF-L and pNF-H levels were measured at least daily during days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r=0.44-0.48; p<0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (M2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p<0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p<0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and GCS. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-to-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

Aptamer Technologies in Neuroscience, Neuro-Diagnostics and Neuro-Medicine Development.

Aptamers developed using in vitro Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology are single-stranded nucleic acids 10-100 nucleotides in length. Their targets, often with specificity and high affinity, range from ions and small molecules to proteins and other biological molecules as well as larger systems, including cells, tissues, and animals. Aptamers often rival conventional antibodies with improved performance, due to aptamers' unique biophysical and biochemical properties, including small size, synthetic accessibility, facile modification, low production cost, and low immunogenicity. Therefore, there is sustained interest in engineering and adapting aptamers for many applications, including diagnostics and therapeutics. Recently, aptamers have shown promise as early diagnostic biomarkers and in precision medicine for neurodegenerative and neurological diseases. Here, we critically review neuro-targeting aptamers and their potential applications in neuroscience research, neuro-diagnostics, and neuro-medicine. We also discuss challenges that must be overcome, including delivery across the blood-brain barrier, increased affinity, and improved in vivo stability and in vivo pharmacokinetic properties.

The Prognostic Role of Candidate Serum Biomarkers in the Post-Acute and Chronic Phases of Disorder of Consciousness: A Preliminary Study.

INTRODUCTION: Serum biomarkers, such as Neurofilament Light (NF-L), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase (UCH-L1), and Total-tau (T-Tau) have been proposed for outcome prediction in the acute phase of severe traumatic brain injury, but they have been less investigated in patients with prolonged DoC (p-DoC). METHODS: We enrolled 25 p-DoC patients according to the Coma Recovery Scale-Revised (CRS-R). We identified different time points: injury onset (t0), first blood sampling at admission in Neurorehabilitation (t1), and second blood sampling at discharge (t2). Patients were split into improved (improved level of consciousness from t1 to t2) and not-improved (unchanged or worsened level of consciousness from t1 to t2). RESULTS: All biomarker levels decreased over time, even though each biomarker reveals typical features. Serum GFAP showed a weak correlation between t1 and t2 (p = 0.001), while no correlation was observed for serum NF-L (p = 0.955), UCH-L1 (p = 0.693), and T-Tau (p = 0.535) between t1 and t2. Improved patients showed a significant decrease in the level of NF-L (p = 0.0001), UCH-L1 (p = 0.001), and T-Tau (p = 0.002), but not for serum GFAP (p = 0.283). No significant statistical differences were observed in the not-improved group. CONCLUSIONS: A significant correlation was found between the level of consciousness improvement and decreased NF-L, UCH-L1, and T-Tau levels. Future studies on the association of serum biomarkers with neurophysiological and neuroimaging prognostic indicators are recommended.

Transcriptomic Signatures of Neuronally Derived Extracellular Vesicles Reveal the Presence of Olfactory Receptors in Clinical Samples from Traumatic Brain Injury Patients.

Traumatic brain injury (TBI) is defined as an injury to the brain by external forces which can lead to cellular damage and the disruption of normal central nervous system functions. The recently approved blood-based biomarkers GFAP and UCH-L1 can only detect injuries which are detectable on CT, and are not sensitive enough to diagnose milder injuries or concussion. Exosomes are small microvesicles which are released from the cell as a part of extracellular communication in normal as well as diseased states. The objective of this study was to identify the messenger RNA content of the exosomes released by injured neurons to identify new potential blood-based biomarkers for TBI. Human severe traumatic brain injury samples were used for this study. RNA was isolated from neuronal exosomes and total transcriptomic sequencing was performed. RNA sequencing data from neuronal exosomes isolated from serum showed mRNA transcripts of several neuronal genes. In particular, mRNAs of several olfactory receptor genes were present at elevated concentrations in the neuronal exosomes. Some of these genes were OR10A6, OR14A2, OR6F1, OR1B1, and OR1L1. RNA sequencing data from exosomes isolated from CSF showed a similar elevation of these olfactory receptors. We further validated the expression of these samples in serum samples of mild TBI patients, and a similar up-regulation of these olfactory receptors was observed. The data from these experiments suggest that damage to the neurons in the olfactory neuroepithelium as well as in the brain following a TBI may cause the release of mRNA from these receptors in the exosomes. Hence, olfactory receptors can be further explored as biomarkers for the diagnosis of TBI.

Effect of Ferric Carboxymaltose Versus Low-Dose Intravenous Iron Therapy and Iron Sucrose on the Total Cost of Care in Patients with Iron Deficiency Anemia: A US Claims Database Analysis.

BACKGROUND AND OBJECTIVE: Iron deficiency is the most common cause of anemia. We compared the effect of ferric carboxymaltose (FCM), low-dose intravenous (IV) iron (LDI), and iron sucrose on total cost of care in patients with iron-deficiency anemia (IDA) from a US health plan perspective. METHODS: We conducted a retrospective claims analysis using the IQVIA PharMetrics Plus database. Patients with index (first) claims of FCM and LDI and a medical claim associated with IDA between 1 January 2017 and 31 December 2019 were included. Monthly total healthcare and inpatient and outpatient costs after receiving index IV iron for patients in the treatment cohorts were compared using a generalized linear model with gamma distribution and log-link. RESULTS: The overall study cohort included 37,655 FCM, 44,237 LDI, and 27,461 iron sucrose patients. Mean per-patient-per-month numbers of IV iron infusions for FCM, LDI, and iron sucrose were 0.20, 0.34, and 0.37, respectively. Compared with baseline, the FCM group had greater reductions in the number of hospital admissions and smaller increases in the number of outpatient visits in the 12 months post-IV iron therapy than LDI and iron sucrose, translating to significantly lower total healthcare cost (post-index adjusted cost ratio for total cost: 0.96 and 0.92, respectively; both P < 0.0001). CONCLUSIONS: Higher drug acquisition cost of FCM relative to LDI and iron sucrose was offset by significantly lower inpatient and outpatient costs in the 12 months post-IV iron therapy. These results support the economic value of FCM for patients with IDA receiving IV iron therapy.

Iron deficiency is one of the most common causes of anemia. Patients with iron deficiency anemia (IDA) may require IV iron replacement therapy. This study was a retrospective claims analysis that utilized medical and pharmacy claims from the IQVIA PharMetrics Plus database. We found that ferric carboxymaltose (FCM), a high-dose formulation of IV iron that delivers up to 1500 mg per course of treatment, was associated with lower inpatient and outpatient costs than low-dose IV iron formulations (LDI) in the 12 months following treatment, offsetting its higher drug acquisition cost relative to LDI. Analysis of subgroups with chronic conditions (cancer, chronic kidney disease, and heart failure) showed greater levels of cost reductions with use of FCM than in the overall study cohort. Findings from this real-world analysis are consistent with previous studies, indicating that FCM was a cost-effective treatment option for IDA.

MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study.

Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.

Isolated Traumatic Subarachnoid Hemorrhage on Head Computed Tomography Scan May Not Be Isolated: A TRACK-TBI Study.

Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) scan is often regarded as a "mild" injury, with reduced need for additional workup. However, tSAH is also a predictor of incomplete recovery and unfavorable outcome. This study aimed to evaluate the characteristics of CT-occult intracranial injuries on brain magnetic resonance imaging (MRI) scan in TBI patients with emergency department (ED) arrival Glasgow Coma Scale (GCS) score 13-15 and isolated tSAH on CT. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI; enrollment years 2014-2019) enrolled participants who presented to the ED and received a clinically-indicated head CT within 24 hours (h) of TBI. A subset of TRACK-TBI participants underwent venipuncture within 24h for plasma glial fibrillary acidic protein (GFAP) analysis, and research MRI at 2-weeks post-injury. In the current study, TRACK-TBI participants aged ≥17 years with ED arrival GCS 13-15, isolated tSAH on initial head CT, plasma GFAP level, and 2-week MRI data were analyzed. In 57 participants, median age was 46.0 years [quartile 1 to 3 (Q1-Q3): 34-57] and 52.6% were male. At ED disposition, 12.3% were discharged home, 61.4% were admitted to hospital ward, and 26.3% to intensive care unit. MRI identified CT-occult traumatic intracranial lesions in 45.6% (26 of 57 participants; 1 additional lesion type: 31.6%; 2 additional lesion types: 14.0%); of these 26 participants with CT-occult intracranial lesions, 65.4% had axonal injury, 42.3% had subdural hematoma, and 23.1% had intracerebral contusion. GFAP levels were higher in participants with CT-occult MRI lesions compared to without (median: 630.6 pg/ml, Q1-Q3: [172.4-941.2] vs. 226.4 [105.8-436.1], p=0.049), and were associated with axonal injury (no: median 226.7 pg/ml [109.6-435.1], yes: 828.6 pg/ml [204.0-1194.3], p=0.009). Our results indicate that isolated tSAH on head CT is often not the sole intracranial traumatic injury in GCS 13-15 TBI. Forty-six percent of patients in our cohort (26 of 57 participants) had additional CT-occult traumatic lesions on MRI. Plasma GFAP may be an important biomarker for the identification of additional CT-occult injuries, including axonal injury. These findings should be interpreted cautiously given our modest sample size and await validation from larger studies.

Data of compressible multi-material flow simulations utilizing an efficient bimaterial Riemann problem solver.

This paper presents fluid dynamics simulation data associated with two test cases in the related research article [1]. In this article, an efficient bimaterial Riemann problem solver is proposed to accelerate multi-material flow simulations that involve complex thermodynamic equations of state and strong discontinuities across material interfaces. The first test case is a one-dimensional benchmark problem, featuring large density jump (4 orders of magnitude) and drastically different thermodynamics relations across a material interface. The second test case simulates the nucleation of a pear-shaped vapor bubble induced by long-pulsed laser in water. This multiphysics simulation combines laser radiation, phase transition (vaporization), non-spherical bubble expansion, and the emission of acoustic and shock waves. Both test cases are performed using the M2C solver, which solves the three-dimensional Eulerian Navier-Stokes equations, utilizing the accelerated bimaterial Riemann solver. Source codes provided in this paper include the M2C solver and a standalone version of the accelerated Riemann problem solver. These source codes serve as references for researchers seeking to implement the acceleration algorithms introduced in the related research article. Simulation data provided include fluid pressure, velocity, density, laser radiance and bubble dynamics. The input files and the workflow to perform the simulations are also provided. These files, together with the source codes, allow researchers to replicate the simulation results presented in the research article, which can be a starting point for new research in laser-induced cavitation, bubble dynamics, and multiphase flow in general.

An Fc-modified monoclonal antibody as novel treatment option for pancreatic cancer.

Pancreatic cancer is a highly lethal disease with limited treatment options. Hence, there is a considerable medical need for novel treatment strategies. Monoclonal antibodies (mAbs) have significantly improved cancer therapy, primarily due to their ability to stimulate antibody-dependent cellular cytotoxicity (ADCC), which plays a crucial role in their therapeutic efficacy. As a result, significant effort has been focused on improving this critical function by engineering mAbs with Fc regions that have increased affinity for the Fc receptor CD16 expressed on natural killer (NK) cells, the major cell population that mediates ADCC in humans. Here we report on the preclinical characterization of a mAb directed to the target antigen B7-H3 (CD276) containing an Fc part with the amino acid substitutions S239D/I332E to increase affinity for CD16 (B7-H3-SDIE) for the treatment of pancreatic cancer. B7-H3 (CD276) is highly expressed in many tumor entities, whereas expression on healthy tissues is more limited. Our findings confirm high expression of B7-H3 on pancreatic cancer cells. Furthermore, our study shows that B7-H3-SDIE effectively activates NK cells against pancreatic cancer cells in an antigen-dependent manner, as demonstrated by the analysis of NK cell activation, degranulation and cytokine release. The activation of NK cells resulted in significant tumor cell lysis in both short-term and long-term cytotoxicity assays. In conclusion, B7-H3-SDIE constitutes a promising agent for the treatment of pancreatic cancer.

Metastatic gastric adenocarcinoma to the cutaneous neck and chest wall.

This case describes an atypical cutaneous presentation of metastatic gastric carcinoma in a patient initially presenting with dysphagia and a sclerotic red plaque overlying the anterior neck and chest. Skin biopsy revealed metastatic adenocarcinoma from the upper gastrointestinal tract. Esophagogastroduodenoscopy revealed stage IV metastatic gastric adenocarcinoma. Treatment with chemotherapy was initiated.

Assessment of Risk Factors and Rate of Conversion to Total Hip Arthroplasty Within 2 Years After Hip Arthroscopy Utilizing a Large Database of Commercially Insured Patients in the United States.

Background: The conversion rate of hip arthroscopy (HA) to total hip arthroplasty (THA) has been reported to be as high as 10%. Despite identifying factors that increase the risk of conversion, current studies do not stratify patients by type of arthroscopic procedure. Purpose/Hypothesis: To analyze the rate and predictors of conversion to THA within 2 years after HA. It was hypothesized that osteoarthritis (OA) and increased patient age would negatively affect the survivorship of HA. Study Design: Cohort study; Evidence level, 3. Methods: The IBM MarketScan database was utilized to identify patients who underwent HA and converted to THA within 2 years at inpatient and outpatient facilities between 2013 and 2017. Patients were split into 3 procedure cohorts as follows: (1) femoroacetabular osteoplasty (FAO), which included treatment for femoroacetabular impingement; (2) isolated debridement; and (3) isolated labral repair. Cohort characteristics were compared using standardized differences. Conversion rates between the 3 cohorts were compared using chi-square tests. The relationship between age and conversion was assessed using linear regression. Predictors of conversion were analyzed using multivariable logistic regression. The median time to conversion was estimated using Kaplan-Meier tests. Results: A total of 5048 patients were identified, and the rates of conversion to THA were 12.86% for isolated debridement, 8.67% for isolated labral repair, and 6.76% for FAO (standardized difference, 0.138). The isolated labral repair cohort had the shortest median time to conversion (isolated labral repair, 10.88 months; isolated debridement, 10.98 months; and FAO, 11.9 months [P = .034). For patients >50 years, isolated debridement had the highest rate of conversion at 18.8%. The conversion rate increased linearly with age. Factors that increased the odds of conversion to THA were OA, having an isolated debridement procedure, and older patient age (P < .05). Conclusion: Older patients and those with preexisting OA of the hip were at a significantly increased risk of failing HA and requiring a total hip replacement within 2 years of the index procedure. Younger patients were at low risk of requiring a conversion procedure no matter which arthroscopic procedure was performed.

Functional Selection of Tau Oligomerization-Inhibiting Aptamers.

Pathological hyperphosphorylation and aggregation of microtubule-associated Tau protein contribute to Alzheimer's Disease (AD) and other related tauopathies. Currently, no cure exists for Alzheimer's Disease. Aptamers offer significant potential as next-generation therapeutics in biotechnology and the treatment of neurological disorders. Traditional aptamer selection methods for Tau protein focus on binding affinity rather than interference with pathological Tau. In this study, we developed a new selection strategy to enrich DNA aptamers that bind to surviving monomeric Tau protein under conditions that would typically promote Tau aggregation. Employing this approach, we identified a set of aptamer candidates. Notably, BW1c demonstrates a high binding affinity (Kd=6.6 nM) to Tau protein and effectively inhibits arachidonic acid (AA)-induced Tau protein oligomerization and aggregation. Additionally, it inhibits GSK3ß-mediated Tau hyperphosphorylation in cell-free systems and okadaic acid-mediated Tau hyperphosphorylation in cellular milieu. Lastly, retro-orbital injection of BW1c tau aptamer shows the ability to cross the blood brain barrier and gain access to neuronal cell body. Through further refinement and development, these Tau aptamers may pave the way for a first-in-class neurotherapeutic to mitigate tauopathy-associated neurodegenerative disorders.

The comparative effectiveness of combined hydrodilatation/corticosteroid procedure with two different quantities for adhesive capsulitis.

OBJECTIVE: To assess the efficacy of injecting various amounts of fluid into the shoulder joints for capsule distension in patients with adhesive capsulitis. DESIGN: A randomized controlled trial. SETTING: Outpatient clinic of a tertiary care centre. PARTICIPANTS: Eighty-four patients with adhesive capsulitis underwent a baseline (time0), 6 weeks (time1), and 12 weeks (time2) follow-up after hydrodilitation. INTERVENTION: Group 1 (n = 42) received 20 ml of lidocaine, steroid, and saline hydrodilatation via posterior glenohumeral recess, while Group 2 (n = 42) received 10 ml of lidocaine, steroid, and saline hydrodilitation. MAIN MEASURES: The primary outcome was the visual analogue scale for pain. The secondary outcomes were shoulder pain and disability index (SPADI) and ROM of the shoulder. RESULTS: There was a significant reduce in VAS scores for pain, SPADI scores, and increased shoulder ROM in both groups over time; however, the group-by-time interactions for any of the outcomes between groups were not significant except VAS pain in motion. Post-hoc pairwise analysis of the marginal effect of time and group showed that the significant difference of VAS in motion is due to time effect: time1 vs time0 (95% CI -4.09 to -2.68), time2 vs time0 (-4.21 to -2.77), and time2 vs time1 (-0.83 to 0.63), without between-group difference: group 1 vs group 2 (-0.38 to 0.59). CONCLUSION: Our study suggests hydrodilatation achieved an optimal effect at time1 for patients with adhesive capsulitis in both groups, and adding more saline offers additional benefits in flexion and external roatation until time2.

The game changer: UCH-L1 and GFAP-based blood test as the first marketed in vitro diagnostic test for mild traumatic brain injury.

INTRODUCTION: Major organ-based in vitro diagnostic (IVD) tests like ALT/AST for the liver and cardiac troponins for the heart are established, but an approved IVD blood test for the brain has been missing, highlighting a gap in medical diagnostics. AREAS COVERED: In response to this need, Abbott Diagnostics secured FDA clearance in 2021 for the i-STAT Alinity™, a point-of-care plasma blood test for mild traumatic brain injury (TBI). BioMerieux VIDAS, also approved in Europe, utilizes two brain-derived protein biomarkers: neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP). These biomarkers, which are typically present in minimal amounts in healthy individuals, are instrumental in diagnosing mild TBI with potential brain lesions. The study explores how UCH-L1 and GFAP levels increase significantly in the bloodstream following traumatic brain injury, aiding in early and accurate diagnosis. EXPERT OPINION: The introduction of the i-STAT Alinity™ and the Biomerieux VIDAS TBI blood tests mark a groundbreaking development in TBI diagnosis. It paves the way for the integration of TBI biomarker tools into clinical practice and therapeutic trials, enhancing the precision medicine approach by generating valuable data. This advancement is a critical step in addressing the long-standing gap in brain-related diagnostics and promises to revolutionize the management and treatment of mild TBI.

Diagnostic Utility of Glial Fibrillary Acidic Protein Beyond 12 Hours After Traumatic Brain Injury: A TRACK-TBI Study.

Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12h of suspected traumatic brain injury (TBI) have been approved by the Food and Drug administration to aid in determining the need for a brain computed tomography (CT) scan. The current study aimed to determine whether this context of use can be expanded beyond 12h post-TBI in patients presenting with Glasgow Coma Scale (GCS) 13-15. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled TBI participants aged ≥17 years who presented to a United States Level 1 trauma center and received a clinically indicated brain CT scan within 24h post-injury, a blood draw within 24h and at 14 days for biomarker analysis. Data from participants with emergency department arrival GCS 13-15 and biomarker values at days 1 and 14 were extracted for the primary analysis. A subgroup of hospitalized participants with serial biomarkers at days 1, 3, 5, and 14 were analyzed, including plasma GFAP and UCH-L1, and serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). The primary analysis compared biomarker values dichotomized by head CT results (CT+/CT-). Area under receiver-operating characteristic curve (AUC) was used to determine diagnostic accuracy. The overall cohort included 1142 participants with initial GCS 13-15, with mean age 39.8 years, 65% male, and 73% Caucasian. The GFAP provided good discrimination in the overall cohort at days 1 (AUC = 0.82) and 14 (AUC = 0.72), and in the hospitalized subgroup at days 1 (AUC = 0.84), 3 (AUC = 0.88), 5 (AUC = 0.82), and 14 (AUC = 0.74). The UCH-L1, NSE, and S100B did not perform well (AUC = 0.51-0.57 across time points). This study demonstrates the utility of GFAP to aid in decision-making for diagnostic brain CT imaging beyond the 12h time frame in patients with TBI who have a GCS 13-15.

Validation of Machine Learning-Aided and Power Line Communication-Based Cable Monitoring Using Measurement Data.

The implementation of power line communications (PLC) in smart electricity grids provides us with exciting opportunities for real-time cable monitoring. In particular, effective fault classification and estimation methods employing machine learning (ML) models have been proposed in the recent past. Often, the research works presenting PLC for ML-aided cable diagnostics are based on the study of synthetically generated channel data. In this work, we validate ML-aided diagnostics by integrating measured channels. Specifically, we consider the concatenation of clustering as a data pre-processing procedure and principal component analysis (PCA)-based dimension reduction for cable anomaly detection. Clustering and PCA are trained with measurement data when the PLC network is working under healthy conditions. A possible cable anomaly is then identified from the analysis of the PCA reconstruction error for a test sample. For the numerical evaluation of our scheme, we apply an experimental setup in which we introduce degradations to power cables. Our results show that the proposed anomaly detector is able to identify a cable degradation with high detection accuracy and low false alarm rate.

Lifelong Chronic Sleep Disruption in a Mouse Model of Traumatic Brain Injury.

Chronic sleep/wake disturbances (SWDs) are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong SWDs. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in 4-month-old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. Sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at 3 months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Further, TBI mice showed extensive brain tissue loss and increased glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 levels in the hypothalamus and vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes post-TBI early in life.

Increased rate of out-of-network surgeon selection for hip arthroscopy compared to more common orthopedic sports procedures.

Background: Demand for hip arthroscopy (HA) has increased, but shortfalls in HA training may create disparities in care access. This analysis aimed to (1) compare out-of-network (OON) surgeon utilization for HA with that of more common orthopedics sports procedures, including rotator cuff repair (RCR), partial meniscectomy (PM), and anterior cruciate ligament reconstruction (ACLR), (2) compare the HA OON surgeon rate with another less commonly performed procedure, meniscus allograft transplant (MAT), and (3) analyze trends and predictors of OON surgeon utilization. Methods: The 2013-2017 IBM MarketScan database identified patients under 65 who underwent HA, RCR, PM, ACLR, or MAT. Demographic differences were determined using standardized differences. Cochran-Armitage tests analyzed trends in OON surgeon utilization. Multivariable logistic regression identified predictors of OON surgeon utilization. Statistical significance was set to p < 0.05 and significant standardized differences were >0.1. Results: 410,487 patients were identified, of which 12,636 patients underwent HA, 87,607 RCR, 233,241 PM, 76,700 ACLR, and 303 MAT. OON surgeon utilization increased for HA, rising from 7.98 % in 2013 to 9.37 % in 2017 (p = 0.026). Compared to RCR, PM, and ACLR, HA was associated with higher likelihood of OON surgeon utilization. Usage of ambulatory surgery centers (ASCs) was predictive of higher OON surgeon rates along with procedure year, insurance plan type, and geographic region. HA performed in an ASC was 13 % less likely to have an OON surgeon (p = 0.047). Conclusion: OON surgeon utilization generally declined but increased for HA. HA was a predictor of OON surgeon status, possibly because HA is a technically complicated procedure with fewer trained in-network providers. Other predictors of OON surgeon status included ASC usage, PPO/EPO plan type, and Northeast geographic region. There is a need to improve access to experienced HA providers-perhaps with prioritization of HA training in residency and fellowship programs-in order to address rising OON surgeon utilization.

Functional connectivity, tissue microstructure and T2 at 11.1 Tesla distinguishes neuroadaptive differences in two traumatic brain injury models in rats: A Translational Outcomes Project in NeuroTrauma (TOP-NT) UG3 phase study.

The damage caused by contusive traumatic brain injuries (TBIs) is thought to involve breakdown in neuronal communication through focal and diffuse axonal injury along with alterations to the neuronal chemical environment, which adversely affects neuronal networks beyond the injury epicenter(s). In the present study, functional connectivity along with brain tissue microstructure coupled with T2 relaxometry were assessed in two experimental TBI models in rat, controlled cortical impact (CCI) and lateral fluid percussive injury (LFPI). Rats were scanned on an 11.1 Tesla scanner on days 2 and 30 following either CCI or LFPI. Naive controls were scanned once and used as a baseline comparison for both TBI groups. Scanning included functional magnetic resonance imaging (fMRI), diffusion weighted images (DWI), and multi-echo T2 images. fMRI scans were analyzed for functional connectivity across laterally and medially located region of interests (ROIs) across the cortical mantle, hippocampus, and dorsal striatum. DWI scans were processed to generate maps of fractional anisotropy, mean, axial, and radial diffusivities (FA, MD, AD, RD). The analyses focused on cortical and white matter (WM) regions at or near the TBI epicenter. Our results indicate that rats exposed to CCI and LFPI had significantly increased contralateral intra-cortical connectivity at 2 days post-injury. This was observed across similar areas of the cortex in both groups. The increased contralateral connectivity was still observed by day 30 in CCI, but not LFPI rats. Although both CCI and LFPI had changes in WM and cortical FA and diffusivities, WM changes were most predominant in CCI and cortical changes in LFPI. Our results provide support for the use of multimodal MR imaging for different types of contusive and skull-penetrating injury.