Update to: Study Pre-protocol for "BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study".

Background: In 2021 we launched the BronchStart study, which collected information on 17,899 presentations in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation's decision to recommend the introduction maternal respiratory syncytial virus (RSV) vaccination, which was introduced in the United Kingdom in August/September 2024.

Study Question: We modified our original protocol to conduct a United Kingdom-wide assessment of maternal vaccination against RSV.

Harnessing Single-Cell Technologies in the Search for New Therapies for Diamond-Blackfan Anemia Syndrome.

The emergence of multiomic single-cell technologies over the last decade has led to improved insights into both normal hematopoiesis and its perturbation in a variety of hematological disorders. Diamond-Blackfan anemia (DBA) syndrome is one such disorder where single-cell assays have helped to delineate the cellular and molecular defects underlying the disease. DBA is caused by heterozygous loss-of-function germline variants in genes encoding ribosomal proteins (RPs).

Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement.

Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care.

OCT based corneal densitometry: the confounding effect of epithelial speckle.

Corneal densitometry is a clinically validated method for objectively assessing the transparency of stroma. The technique is currently dominated by Scheimpflug technology. Still, optical coherence tomography (OCT), in which examination of the statistical properties of corneal speckle is undertaken, has also been considered to assess corneal densitometry.

Measuring intraocular pressure with OCT: the first approach.

The variability of corneal OCT speckle statistics is indirectly related to changes in corneal microstructure, which may be induced by intraocular pressure (IOP). A new approach is considered, which attempts to estimate IOP based on corneal speckle statistics in OCT images. An area () under trajectories of contrast ratio with respect to stromal depth was calculated.

Assessing Age-Related Changes in Corneal Densitometry Parameters With Anterior Segment OCT Speckle.

Purpose: The purpose of this study was to assess in vivo regional variability in the densitometry parameters of corneal stroma and the modulating effect of age on those parameters using statistical characterization of optical coherence tomography (OCT) speckle.

Methods: OCT imaging of central and peripheral cornea was performed in a group of 20 younger (24 to 30 years old) and 19 older (50 to 87 years old) subjects. The sample size was estimated using normal assumptions and previously reported data on speckle parameter variability.

Diamond-Blackfan anemia in adults: In pursuit of a common approach for a rare disease.

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome, usually caused by loss-of function variants in genes encoding ribosomal proteins. The hallmarks of DBA are anemia, congenital anomalies and cancer predisposition. Although DBA usually presents in childhood, the prevalence in later life is increasing due to an expanding repertoire of implicated genes, improvements in genetic diagnosis and increasing life expectancy.

Assessing and compensating for the confounding factors in Scheimpflug-based corneal densitometry.

Scheimpflug-based corneal densitometry is a clinically verified method for assessing corneal transparency. Nevertheless, the estimates of corneal densitometry appear to be correlated with age and eye biometry parameters, such as the anterior chamber depth or the pupil size, and that ensues a convoluted conditional estimation problem, where it is difficult to interpret the results. This study aims at devising a methodology for compensating for such confounding factors by using, as a research platform, a commercially available Scheimpflug camera that allows exporting images in a dynamic fashion, allowing averaging the results from multiple acquisitions.

Age-related changes in dynamic corneal backscatter observed in Scheimpflug imaging.

Corneal visualization Scheimpflug technology (Corvis ST) has the potential to indirectly provide information on corneal structure via the analysis of statistical properties of the backscatter. The aim of this work was to ascertain whether there are age-related changes in the dynamics of corneal backscatter during an air-puffed induced corneal deformation. Retrospective data from Corvis ST measurements of 151 young subjects (19-30 years) and 82 older subjects (50-87 years) were considered.

Indirectly assessing changes in corneal properties with OCT speckle after crosslinking in porcine eyes.

The aim of this study was to assess the effect of the standard crosslinking (CXL) procedure on corneal properties and subsequent changes in collagen bonds formation using optical coherence tomography (OCT) corneal speckle statistics and vibrational spectroscopy. Porcine eyes with intact corneal epithelium were randomly selected to one of the four study groups: (1) untreated eyes moistened with phosphate-buffered saline (PBS); (2) eyes after the epithelial debridement and riboflavin application; (3) eyes after CXL procedure according to the Dresden protocol; and (4) eyes after corneal epithelial debridement, regularly moistened with PBS. Before and after this selection, each eyeball was subjected to the constant intraocular pressure of 20 mmHg.

Tear Film Surface Quality in Modern Daily Disposable Contact Lens Wear.

Objectives: As reported previously, tear film surface quality (TFSQ) should be considered in contact lens (CL) fitting. This study followed noninvasive keratograph tear film break-up time (NIKBUT) in CL wearers for 12 months to validate its clinical utility in predicting CL performance.

Methods: Fifty-five subjects (M/F=17/38) aged 26±4 years were prescribed silicone hydrogel or hydrogel CLs.

Statistical analysis of corneal OCT speckle: a non-parametric approach.

In biomedical optics, it is often of interest to statistically model the amplitude of the speckle using some distributional approximations with their parameters acting as biomarkers. In this paper, a paradigm shift is being advocated in which non-parametric approaches are used. Specifically, a range of distances, evaluated in different domains, between an empirical non-parametric distribution of the normalized speckle amplitude sample and the benchmark Rayleigh distribution, is considered.

Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development.

Human hematopoiesis is a dynamic process that starts in utero 18-21 days post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartment changes during human ontogeny and the underlying gene regulatory mechanisms, we compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime.

Glaucoma classification based on scanning laser ophthalmoscopic images using a deep learning ensemble method.

This study aimed to assess the utility of optic nerve head (onh) en-face images, captured with scanning laser ophthalmoscopy (slo) during standard optical coherence tomography (oct) imaging of the posterior segment, and demonstrate the potential of deep learning (dl) ensemble method that operates in a low data regime to differentiate glaucoma patients from healthy controls. The two groups of subjects were initially categorized based on a range of clinical tests including measurements of intraocular pressure, visual fields, oct derived retinal nerve fiber layer (rnfl) thickness and dilated stereoscopic examination of onh. 227 slo images of 227 subjects (105 glaucoma patients and 122 controls) were used.

Corneal Optical Coherence Tomography Speckle in Crosslinked and Untreated Rabbit Eyes in Response to Elevated Intraocular Pressure.

Purpose: To ascertain the influence of intraocular pressure (IOP) on corneal optical coherence tomography (OCT) speckle in untreated and ultraviolet A-riboflavin induced corneal collagen crosslinked rabbit eyes.

Methods: Left corneas of eight rabbits were de-epithelialized and crosslinked by applying riboflavin and 30-minute ultraviolet A light exposure. After enucleation (6 months after treatment), each eyeball (treated and untreated) was mounted in a measurement setup, in which IOP was increased from 15 to 45 mm Hg in steps of 5 mm Hg.

The effect of intraocular pressure elevation and related ocular biometry changes on corneal OCT speckle distribution in porcine eyes.

The aim of this study was to evaluate the influence of increase in intraocular pressure (IOP) and cooccurring changes in ocular biometry parameters on the corneal optical coherence tomography (OCT) speckle distribution in ex-vivo experiments on porcine intact eyes. Twenty-three eyeballs were used in the inflation test where IOP in the anterior chamber was precisely set from 10 mmHg to 40 mmHg in steps of 5 mmHg and where eye biometry was utilized (IOL Master 700). To assess the influence of the duration of the experiment on the OCT speckle statistics, the second experiment was performed with 10 eyeballs at the constant IOP of 15 mmHg.

Associating the biomarkers of ocular blood flow with lamina cribrosa parameters in normotensive glaucoma suspects. Comparison to glaucoma patients and healthy controls.

Purpose: To evaluate association between ocular blood flow biomarkers and lamina cribrosa parameters in normotensive glaucoma suspects compared to glaucoma patients and healthy controls.

Methods: A total of 211 subjects (72 normotensive glaucoma suspects, 70 with primary open-angle glaucoma and 69 controls) were included. Ocular blood flow biomarkers in ophthalmic artery, central retinal artery, as well as in nasal and temporal short posterior ciliary arteries were measured using colour Doppler imaging.

Reducing the Number of MEG/EEG Trials Needed for the Estimation of Brain Evoked Responses: A Bootstrap Approach.

Objective: A common problem in magnetoencephalographic (MEG) and electroencephalographic (EEG) experimental paradigms relying on the estimation of brain evoked responses is the lengthy time of the experiment, which stems from the need to acquire a large number of repeated recordings. Using a bootstrap approach, we aim at reliably reducing the number of these repeated trials.

Methods: To this end, we assessed five variants of non-parametric bootstrapping based on the classical signal-plus-noise model constituting the foundation of signal averaging in MEG/EEG.

The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma.

Multiple myeloma is a malignancy of plasma cells initiated and driven by primary and secondary genetic events. However, myeloma plasma cell survival and proliferation might be sustained by non-genetic drivers. Z-DNA-binding protein 1 (ZBP1; also known as DAI) is an interferon-inducible, Z-nucleic acid sensor that triggers RIPK3-MLKL-mediated necroptosis in mice.

Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a poor-prognosis childhood leukemia usually caused by RAS-pathway mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population.

Keratoconus Detection Based on a Single Scheimpflug Image.

Purpose: To introduce a new approach for keratoconus detection based on corneal microstructure observed in vivo derived from a single Scheimpflug image.

Methods: Scheimpflug single-image snapshots from 25 control subjects and 25 keratoconus eyes were analyzed; from each group, five subjects were randomly selected to provide out-of-sample data. Each corneal image was segmented, after which the stromal pixel intensities were statistically modeled with a Weibull distribution.

Omnibus test for normality based on the Edgeworth expansion.

Statistical inference in the form of hypothesis tests and confidence intervals often assumes that the underlying distribution is normal. Similarly, many signal processing techniques rely on the assumption that a stationary time series is normal. As a result, a number of tests have been proposed in the literature for detecting departures from normality.