The Use of Heart Rate Responses Extracted From Functional Near-Infrared Spectroscopy Data as a Measure of Speech Discrimination Ability in Sleeping Infants.

OBJECTIVES: Cardiac responses (e.g., heart rate changes) due to an autonomous response to sensory stimuli have been reported in several studies. This study investigated whether heart rate information extracted from functional near-infrared spectroscopy (fNIRS) data can be used to assess the discrimination of speech sounds in sleeping infants. This study also investigated the adaptation of the heart rate response over multiple, sequential stimulus presentations. DESIGN: fNIRS data were recorded from 23 infants with no known hearing loss, aged 2 to 10 months. Speech syllables were presented using a habituation/dishabituation test paradigm: the infant's heart rate response was first habituated by repeating blocks of one speech sound; then, the heart rate response was dishabituated with the contrasting (novel) speech sound. This stimulus presentation sequence was repeated for as long as the infants were asleep. RESULTS: The group-level average heart rate response to the novel stimulus was greater than that to the habituated first sound, indicating that sleeping infants were able to discriminate the speech sound contrast. A significant adaptation of the heart rate responses was seen over the session duration. CONCLUSION: The dishabituation response could be a valuable marker for speech discrimination, especially when used in conjunction with the fNIRS hemodynamic response.

Rapid near-atomic resolution single-particle 3D reconstruction with SIMPLE.

Cryogenic electron microscopy (cryo-EM) and single-particle analysis enables determination of near-atomic resolution structures of biological molecules. However, large computational requirements limit throughput and rapid testing of new image processing tools. We developed PRIME, an algorithm part of the SIMPLE software suite, for determination of the relative 3D orientations of single-particle projection images. PRIME has primarily found use for generation of an initial ab initio 3D reconstruction. Here we show that the strategy behind PRIME, iterative estimation of per-particle orientation distributions with stochastic hill climbing, provides a competitive approach to near-atomic resolution single-particle 3D reconstruction. A number of mathematical techniques for accelerating the convergence rate are introduced, leading to a speedup of nearly two orders of magnitude. We benchmarked our developments on numerous publicly available data sets and conclude that near-atomic resolution ab initio 3D reconstructions can be obtained with SIMPLE in a matter of hours, using standard over-the-counter CPU workstations.

CPD in the remote environment: a role for practice-based small group learning?

BACKGROUND: Continuous professional development (CPD) is recognised as essential and mandated by the Royal College of General Practitioners and other medical professional colleges. However, it can be difficult to maintain when deployed and remote from normal training and support structures. There is no literature directly discussing how military doctors in the deployed and remote environment maintain CPD and if practice-based small group learning (PBSGL) could be an appropriate tool to facilitate this in future. AIM: To describe the CPD experience of medical officers (MOs) working for the Defence Medical Services (DMS) and assess if offering PBSGL would be welcomed and likely beneficial. DESIGN AND SETTING: This is a quantitative survey of doctors working in primary care within the DMS. METHOD: A questionnaire was designed to elicit opinions, current practice and previous experience of CPD within the deployed and firm base environments. It also aimed to elicit prior experience of and appetite for PBSGL as a solution. This was then distributed via email to MOs working for the DMS. RESULTS: 130 responses (25%) were received. 122 (96%) had heard of PBSGL, 56% had participated in PBSGL in the firm base. 60% agreed or strongly agreed PBSGL was an effective way to maintain CPD. 73% reported eLearning as a mode of maintaining CPD while deployed or working in a remote environment. CONCLUSION: This study demonstrated that many general practitioners deployed to remote locations feel that CPD provision could be improved and that PBSGL is a potential solution.

Inhaled methoxyflurane (Penthrox) for analgesia in trauma: a systematic review protocol.

BACKGROUND: More than 75% of patients presenting to the Emergency Department are suffering symptoms of pain. Despite this, 67% will not receive any analgesia. Methoxyflurane is a fluorinated hydrocarbon gas which has analgesic properties when inhaled. Penthrox is a methoxyflurane autoinhaler recently licenced in Europe. Its ease of administration, safety, and fast onset of action make it of particular relevance to emergency medicine. Additionally, outside the hospital, it has the advantage of increased temperature stability and portability over current standard care. New evidence of its efficacy is emerging; however, currently, its use in Europe is not widespread. The objective of this study will be to systematically evaluate the evidence on inhaled methoxyflurane to determine if it is a superior analgesia in the acute trauma setting. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis on randomised controlled trials, comparing inhaled methoxyflurane and either placebo or standard care. A comprehensive search will be conducted from database inception onwards in MEDLINE, Embase, and the Cochrane CENTRAL database, concurrent with a search of the grey literature for other relevant studies, including clinical trial databases. Only randomised controlled trials will be included. No limitations will be imposed on publication status or language of publication. The primary outcome will be mean difference in patient-reported pain at time points within the first 30 min of administration. Secondary outcomes will be mean difference in time to clinically significant pain relief and relative risk of adverse effects. Two reviewers will independently screen all returned studies and collect data. Disagreements will be resolved through discussion or referral to a third reviewer. Individual study methodological quality will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis; if this is not possible, we will construct a narrative synthesis. DISCUSSION: This systematic review will summarise the best available evidence and definitively establish if inhaled methoxyflurane is a superior analgesia to standard care in the acute trauma setting. This knowledge will directly impact emergency care in the UK and worldwide and may require amendments to European pain relief guidelines. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020189119 .

Speech token detection and discrimination in individual infants using functional near-infrared spectroscopy.

Speech detection and discrimination ability are important measures of hearing ability that may inform crucial audiological intervention decisions for individuals with a hearing impairment. However, behavioral assessment of speech discrimination can be difficult and inaccurate in infants, prompting the need for an objective measure of speech detection and discrimination ability. In this study, the authors used functional near-infrared spectroscopy (fNIRS) as the objective measure. Twenty-three infants, 2 to 10 months of age participated, all of whom had passed newborn hearing screening or diagnostic audiology testing. They were presented with speech tokens at a comfortable listening level in a natural sleep state using a habituation/dishabituation paradigm. The authors hypothesized that fNIRS responses to speech token detection as well as speech token contrast discrimination could be measured in individual infants. The authors found significant fNIRS responses to speech detection in 87% of tested infants (false positive rate 0%), as well as to speech discrimination in 35% of tested infants (false positive rate 9%). The results show initial promise for the use of fNIRS as an objective clinical tool for measuring infant speech detection and discrimination ability; the authors highlight the further optimizations of test procedures and analysis techniques that would be required to improve accuracy and reliability to levels needed for clinical decision-making.

Cartilage-like composition of keloid scar extracellular matrix suggests fibroblast mis-differentiation in disease.

Following wound damage to the skin, the scarring spectrum is wide-ranging, from a manageable normal scar through to pathological keloids. The question remains whether these fibrotic lesions represent simply a quantitative extreme, or alternatively, whether they are qualitatively distinct. A three-way comparison of the extracellular matrix (ECM) composition of normal skin, normal scar and keloids was performed using quantitative discovery-based proteomics. This approach identified 40 proteins that were significantly altered in keloids compared to normal scars, and strikingly, 23 keloid-unique proteins. The major alterations in keloids, when functionally grouped, showed many changes in proteins involved in ECM assembly and fibrillogenesis, but also a keloid-associated loss of proteases, and a unique cartilage-like composition, which was also evident histologically. The presence of Aggrecan and Collagen II in keloids suggest greater plasticity and mis-differentiation of the constituent cells. This study characterises the ECM of both scar types to a depth previously underappreciated. This thorough molecular description of keloid lesions relative to normal scars is an essential step towards our understanding of this debilitating clinical problem, and how best to treat it.

Single-particle cryo-EM-Improved ab initio 3D reconstruction with SIMPLE/PRIME.

Cryogenic electron microscopy (cryo-EM) and single-particle analysis now enables the determination of high-resolution structures of macromolecular assemblies that have resisted X-ray crystallography and other approaches. We developed the SIMPLE open-source image-processing suite for analysing cryo-EM images of single-particles. A core component of SIMPLE is the probabilistic PRIME algorithm for identifying clusters of images in 2D and determine relative orientations of single-particle projections in 3D. Here, we extend our previous work on PRIME and introduce new stochastic optimization algorithms that improve the robustness of the approach. Our refined method for identification of homogeneous subsets of images in accurate register substantially improves the resolution of the cluster centers and of the ab initio 3D reconstructions derived from them. We now obtain maps with a resolution better than 10 Å by exclusively processing cluster centers. Excellent parallel code performance on over-the-counter laptops and CPU workstations is demonstrated.

Brain morphometry in blind and sighted subjects.

Previous neuroimaging studies have demonstrated structural brain alterations in blind subjects, but most have focused on primary open angle glaucoma or retinopathy of prematurity, used low-field scanners, a limited number of receive channels, or have presented uncorrected results. We recruited 10 blind and 10 age and sex-matched controls to undergo high-resolution MRI using a 3T scanner and a 32-channel receive coil. We evaluated whole-brain morphological differences between the groups as well as manual segmentation of regional hippocampal volumes. There were no hippocampal volume differences between the groups. Whole-brain morphometry showed white matter volume differences between blind and sighted groups including localised larger regions in the visual cortex (occipital gyral volume and thickness) among those with blindness early in life compared to those with blindness later in life. Hence, in our patients, blindness resulted in brain volumetric differences that depend upon duration of blindness.