Window into the mind: Advanced handheld spectroscopic eye-safe technology for point-of-care neurodiagnostic.

Traumatic brain injury (TBI), a major cause of morbidity and mortality worldwide, is hard to diagnose at the point of care with patients often exhibiting no clinical symptoms. There is an urgent need for rapid point-of-care diagnostics to enable timely intervention. We have developed a technology for rapid acquisition of molecular fingerprints of TBI biochemistry to safely measure proxies for cerebral injury through the eye, providing a path toward noninvasive point-of-care neurodiagnostics using simultaneous Raman spectroscopy and fundus imaging of the neuroretina. Detection of endogenous neuromarkers in porcine eyes' posterior revealed enhancement of high-wave number bands, clearly distinguishing TBI and healthy cohorts, classified via artificial neural network algorithm for automated data interpretation. Clinically, translating into reduced specialist support, this markedly improves the speed of diagnosis. Designed as a hand-held cost-effective technology, it can allow clinicians to rapidly assess TBI at the point of care and identify long-term changes in brain biochemistry in acute or chronic neurodiseases.

Comparison of Screw Quantity and Placement of Metacarpal Fracture Fixation: A Biomechanical Study.

BACKGROUND: It is recommended to have 6 bicortical screws for plate fixation of long bone fractures; however, many metacarpal fractures do not allow 6 screws due to size limitations and proximity of crucial anatomical structures. The purpose of this biomechanical study was to determine whether the mechanical properties of a 4-screw nonlocking construct are noninferior to those of a 6-screw nonlocking construct. METHODS: Metacarpal sawbones were used to simulate a midshaft, transverse fracture. Nonlocking bicortical screws were placed in the 6-hole plate, and the metacarpals were randomly assigned to 2 equal study groups: (1) 4 screws, 2 on either side of the fracture (4S); and (2) 6 screws, 3 on either side of the fracture (6S). The metacarpals were tested in a cyclic loading mode and load to failure in a cantilever bending mode. RESULTS: Maximum deflection was significantly higher for 4S compared with 6S. Cyclic root mean square (RMS) was also significantly greater for 4S at 70 and 100 N. There were no statistically significant differences observed between the 2 constructs for maximum bending load, bending stiffness, and cyclic RMS at 40 N. The maximum bending load in 4S and 6S was 245.6 ± 37.9 N and 230.8 ± 41.9 N, respectively; 4S was noninferior and not superior to 6S. Noninferiority testing was inconclusive for bending stiffness. CONCLUSIONS: A 4-screw bicortical nonlocking construct is noninferior to a 6-screw bicortical nonlocking construct for fixation of metacarpal fractures, which may be advantageous to minimize disruption of soft tissues while maintaining sufficient construct stability.

Spectroscopic molecular-fingerprint profiling of saliva.

Saliva analysis has been gaining interest as a potential non-invasive source of disease indicative biomarkers due to being a complex biofluid correlating with blood-based constituents on a molecular level. For saliva to cement its usage for analytical applications, it is paramount to gain underpinning molecular knowledge and establish a 'baseline' of the salivary composition in healthy individuals as well as characterize how these factors are impacting its performance as potential analytical biofluid. Here, we have systematically studied the molecular spectral fingerprint of saliva, including the changes associated with gender, age, and time. Via hybrid artificial neural network algorithms and Raman spectroscopy, we have developed a non-destructive molecular profiling approach enabling the assessment of salivary spectral changes yielding the determination of gender and age of the biofluid source. Our classification algorithm successfully identified the gender and age from saliva with high classification accuracy. Discernible spectral molecular 'barcodes' were subsequently constructed for each class and found to primarily stem from amino acid, protein, and lipid changes in saliva. This unique combination of Raman spectroscopy and advanced machine learning techniques lays the platform for a variety of applications in forensics and biosensing.

Spectroscopic profiling variations in extracellular vesicle biochemistry in a model of myogenesis.

Extracellular vesicles (EVs) hold value as accessible biomarkers for understanding cellular differentiation and related pathologies. Herein, EV biomarkers in models of skeletal muscle dormancy and differentiation have been comparatively profiled using Raman spectroscopy (RS). Significant variations in the biochemical fingerprint of EVs were detected, with an elevation in peaks associated with lipid and protein signatures during early myogenic differentiation (day 2). Principal component analysis revealed a clear separation between the spectra of EVs derived from myogenic and senescent cell types, with non-overlapping interquartile ranges and population median. Observations aligned with nanoparticle tracking data, highlighting a significant early reduction in EV concentration in senescent myoblast cultures as well as notable variations in EV morphology and diameter. As differentiation progressed physical and biochemical differences in the properties of EVs became less pronounced. This study demonstrates the applicability of RS as a high-resolution analytical method for profiling biochemical changes in EVs during early myogenesis.

The Valsalva maneuver: an indispensable physiological tool to differentiate intra versus extracranial near-infrared signal.

Developing near-infrared spectroscopy (NIRS) parameter recovery techniques to more specifically resolve brain physiology from that of the overlying tissue is an important part of improving the clinical utility of the technology. The Valsalva maneuver (VM) involves forced expiration against a closed glottis causing widespread venous congestion within the context of a fall in cardiac output. Due to the specific anatomical confines and metabolic demands of the brain we believe a properly executed VM has the ability to separate haemodynamic activity of brain tissue from that of the overlying scalp as observed by NIRS, and confirmed by functional magnetic resonance imaging (fMRI). Healthy individuals performed a series of standing maximum effort VMs under separate observation by frequency domain near-infrared spectroscopy (FD-NIRS) and fMRI. Nine individuals completed the clinical protocol (6 males, age 21-40). During the VMs, brain and extracranial tissue targeted signal were significantly different (opposite direction of change) in both fMRI and NIRS (p=0.00025 and 0.00115 respectively), with robust cross correlation of parameters between modalities. Four of these individuals performed further VMs after infiltrating 2% xylocaine/1:100,000 epinephrine (vasoconstrictor) into scalp tissue beneath the probes. No significant difference in the cerebrally derived parameters was observed. The maximum effort VM has the ability to separate NIRS observable physiology of the brain from the overlying extracranial tissue. Observations made by this FD cerebral NIRS device are comparable with fMRI in this context.

Development of the Self Optimising Kohonen Index Network (SKiNET) for Raman Spectroscopy Based Detection of Anatomical Eye Tissue.

Raman spectroscopy shows promise as a tool for timely diagnostics via in-vivo spectroscopy of the eye, for a number of ophthalmic diseases. By measuring the inelastic scattering of light, Raman spectroscopy is able to reveal detailed chemical characteristics, but is an inherently weak effect resulting in noisy complex signal, which is often difficult to analyse. Here, we embraced that noise to develop the self-optimising Kohonen index network (SKiNET), and provide a generic framework for multivariate analysis that simultaneously provides dimensionality reduction, feature extraction and multi-class classification as part of a seamless interface. The method was tested by classification of anatomical ex-vivo eye tissue segments from porcine eyes, yielding an accuracy >93% across 5 tissue types. Unlike traditional packages, the method performs data analysis directly in the web browser through modern web and cloud technologies as an open source extendable web app. The unprecedented accuracy and clarity of the SKiNET methodology has the potential to revolutionise the use of Raman spectroscopy for in-vivo applications.

Cerebral Oxygenation in Traumatic Brain Injury: Can a Non-Invasive Frequency Domain Near-Infrared Spectroscopy Device Detect Changes in Brain Tissue Oxygen Tension as Well as the Established Invasive Monitor?

The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma center were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilized to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mm Hg, respectively) as measured invasively. Sixteen individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in nine of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576-0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.

Frequency-domain vs continuous-wave near-infrared spectroscopy devices: a comparison of clinically viable monitors in controlled hypoxia.

The Near-infrared spectroscopy (NIRS) has not been adopted as a mainstream monitoring modality in acute neurosurgical care due to concerns about its reliability and consistency. However, improvements in NIRS parameter recovery techniques are now available that may improve the quantitative accuracy of NIRS for this clinical context. Therefore, the aim of this study was to compare the abilities of a continuous-wave (CW) NIRS device with a similarly clinically viable NIRS device utilising a frequency-domain (FD) parameter recovery technique in detecting changes in cerebral tissue saturation during stepwise increases of experimentally induced hypoxia. Nine healthy individuals (6M/3F) underwent a dynamic end-tidal forced manipulation of their expiratory gases to induce a stepwise induced hypoxia. The minimum end-tidal oxygen partial pressure (EtO2) achieved was 40 mm Hg. Simultaneous neurological and extra-cranial tissue NIRS reading were obtained during this protocol by both tested devices. Both devices detected significant changes in cerebral tissue saturation during the induction of hypoxia (CW 9.8 ± 2.3 %; FD 7.0 ± 3.4 %; Wilcoxon signed rank test P < 0.01 for both devices). No significant difference was observed between the saturation changes observed by either device (P = 0.625). An observably greater degree of noise was noticed in parameters recovered by the FD device, and both demonstrated equally variable baseline readings (Coefficient of variance 8.4 and 9.7 % for the CW and FD devices, respectively) between individuals tested. No advantageous difference was observed in parameters recovered from the FD device compared with those detected by CW.

Improving the quantitative accuracy of cerebral oxygen saturation in monitoring the injured brain using atlas based Near Infrared Spectroscopy models.

The application of Near Infrared Spectroscopy (NIRS) for the monitoring of the cerebral oxygen saturation within the brain is well established, albeit using temporal data that can only measure relative changes of oxygenation state of the brain from a baseline. The focus of this investigation is to demonstrate that hybridisation of existing near infrared probe designs and reconstruction techniques can pave the way to produce a system and methods that can be used to monitor the absolute oxygen saturation in the injured brain. Using registered Atlas models in simulation, a novel method is outlined by which the quantitative accuracy and practicality of NIRS for specific use in monitoring the injured brain, can be improved, with cerebral saturation being recovered to within 10.1 ± 1.8% of the expected values.

Near-Infrared Spectroscopy in the Monitoring of Adult Traumatic Brain Injury: A Review.

Cerebral near-infrared spectroscopy (NIRS) has long represented an exciting prospect for the noninvasive monitoring of cerebral tissue oxygenation and perfusion in the context of traumatic brain injury (TBI), although uncertainty still exists regarding the reliability of this technology specifically within this field. We have undertaken a review of the existing literature relating to the application of NIRS within TBI. We discuss current "state-of-the-art" NIRS monitoring, provide a brief background of the technology, and discuss the evidence regarding the ability of NIRS to substitute for established invasive monitoring in TBI.

A noninvasive method for in situ determination of mating success in female American lobsters (Homarus americanus).

Despite being one of the most productive fisheries in the Northwest Atlantic, much remains unknown about the natural reproductive dynamics of American lobsters. Recent work in exploited crustacean populations (crabs and lobsters) suggests that there are circumstances where mature females are unable to achieve their full reproductive potential due to sperm limitation. To examine this possibility in different regions of the American lobster fishery, a reliable and noninvasive method was developed for sampling large numbers of female lobsters at sea. This method involves inserting a blunt-tipped needle into the female's seminal receptacle to determine the presence or absence of a sperm plug and to withdraw a sample that can be examined for the presence of sperm. A series of control studies were conducted at the dock and in the laboratory to test the reliability of this technique. These efforts entailed sampling 294 female lobsters to confirm that the presence of a sperm plug was a reliable indicator of sperm within the receptacle and thus, mating. This paper details the methodology and the results obtained from a subset of the total females sampled. Of the 230 female lobsters sampled from George's Bank and Cape Ann, MA (size range = 71-145 mm in carapace length), 90.3% were positive for sperm. Potential explanations for the absence of sperm in some females include: immaturity (lack of physiological maturity), breakdown of the sperm plug after being used to fertilize a clutch of eggs, and lack of mating activity. The surveys indicate that this technique for examining the mating success of female lobsters is a reliable proxy that can be used in the field to document reproductive activity in natural populations.

Pressure redistribution devices: what works, at what cost and what's next?

This article discusses the development and usage of pressure redistribution devices (PRDs) and their impact on the prevention and treatment of pressure ulcers within the NHS. The article outlines the history of the development of these devices and discusses the reasons for a lack of substantial evidence in support of the use of these devices, their impact on the NHS on cost and perceived outcome. The article describes the typical usage profile in a 500 bed NHS hospital and concludes with a view as to how that may change in the future.