Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Acknowledgements The authors are indebted to the participants and parents who have already been recruited. We also acknowledge the enthusiasm and endeavour of the research nurse team which includes: Stephen Main, Margaret Connon, Catherine Beveridge, Julie Baggott, Kay Riding, Ellie McCamie, Maria Larsson, Lynda Melvin, Mumtaz Idris, Tara Murray, Nicky Tongue, Nicolene Plaatjies, Sheila Mortimer, Sally Spedding, Susy Grevatt, Victoria Welch, Morag Zelisko, Jillian Doherty, Jane Martin, Emma Macleod and Cilla Snape. We are also delighted to be working alongside the following colleagues in laboratories: Marie Craigon, Marie McWilliam, Maria Zarconi, Judit Barabas, Lindsay Broadbent, Ceyda Oksel and Sheerien Manzoor. Grant information The study is supported by the Wellcome Trust [108818]; and the PHA HSC R&D Division, Northern Ireland.Peer reviewedPublisher PD

Feeder layer- and animal product-free culture of neonatal foreskin keratinocytes: improved performance, usability, quality and safety

Since 1987, keratinocytes have been cultured at the Queen Astrid Military Hospital. These keratinocytes have been used routinely as auto and allografts on more than 1,000 patients, primarily to accelerate the healing of burns and chronic wounds. Initially the method of Rheinwald and Green was used to prepare cultured epithelial autografts, starting from skin samples from burn patients and using animal-derived feeder layers and media containing animal-derived products. More recently we systematically optimised our production system to accommodate scientific advances and legal changes. An important step was the removal of the mouse fibroblast feeder layer from the cell culture system. Thereafter we introduced neonatal foreskin keratinocytes (NFK) as source of cultured epithelial allografts, which significantly increased the consistency and the reliability of our cell production. NFK master and working cell banks were established, which were extensively screened and characterised. An ISO 9001 certified Quality Management System (QMS) governs all aspects of testing, validation and traceability. Finally, as far as possible, animal components were systematically removed from the cell culture environment. Today, quality controlled allograft production batches are routine and, due to efficient cryopreservation, stocks are created for off-the-shelf use. These optimisations have significantly increased the performance, usability, quality and safety of our allografts. This paper describes, in detail, our current cryopreserved allograft production process

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO\u2082, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV\u2081) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 \u3bcg\ub7m(-3) increase in NO\u2082 exposure was associated with lower levels of FEV\u2081 (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 \u3bcg\ub7m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV\u2081 (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe

Correction to: Assessing real-world gait with digital technology? Validation, insights and recommendations from the Mobilise-D consortium (<em>Journal of NeuroEngineering and Rehabilitation</em>, (2023), 20, 1, (78), 10.1186/s12984-023-01198-5)

\ua9 The Author(s) 2024.Following publication of the original article [1], the author noticed the errors in Table 1, and in Discussion section. In Table 1 under Metric (Gait sequence detection) column, the algorithms GSDB was updated with wrong description, input, output, language and citation and GSDc with wrong description has been corrected as shown below: (Table presented.) Description of algorithms for each metric: gait sequence detection (GSD), initial contact event detection (ICD), cadence estimation (CAD) and stride length estimation (SL) Metric Name Description Input Output Language References GSDA Based on a frequency-based approach, this algorithm is implemented on the vertical and anterior–posterior acceleration signals. First, these are band pass filtered to keep frequencies between 0.5 and 3 Hz. Next, a convolution of a 2 Hz sinewave (representing a template for a gait cycle) is performed, from which local maxima will be detected to define the regions of gait acc_v: vertical acceleration acc_ap: anterior–posterior acceleration WinS = 3 s; window size for convolution OL = 1.5 s; overlap of windows Activity_thresh = 0.01; Motion threshold Fs: sampling frequency Start: beginning of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector End: termination of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector Matlab\uae Iluz, Gazit [40] GSDB This algorithm, based on a time domain-approach, detects the gait periods based on identified steps. First, the norm of triaxial acceleration signal is low-pass filtered (FIR, fc = 3.2 Hz), then a peak detection procedure using a threshold of 0.1 [g] is applied to identify steps. Consecutive steps, detected using an adaptive step duration threshold are associated to gait sequences acc_norm: norm of the 3D-accelerometer signal Fs: sampling frequency th: peak detection threshold: 0.1 (g) Start: beginning of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector End: termination of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector Matlab\uae Paraschiv-Ionescu, Newman [41] GSDc This algorithm utilizes the same approach as GSDBthe only difference being a different threshold for peak detection of 0.15 [g] acc_norm: norm of the 3D-accelerometer signal Fs: sampling frequency th: peak detection threshold: 0.15 (g) Start: beginning of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector End: termination of N gait sequences [s] relative to the start of a recording or a test/trial. Format: 1 7 N vector Matlab\uae Paraschiv-Ionescu, Newman [41] In Discussion section, the paragraph should read as "Based on our findings collectively, we recommend using GSDB on cohorts with slower gait speeds and substantial gait impairments (e.g., proximal femoral fracture). This may be because this algorithm is based on the acceleration norm (overall accelerometry signal rather than a specific axis/direction (e.g., vertical), hence it is more robust to sensor misalignments that are common in unsupervised real-life settings. Moreover, the use of adaptive threshold, that are derived from the features of a subject’s data and applied to step duration for detection of steps belonging to gait sequences, allows increased robustness of the algorithm to irregular and unstable gait patterns" instead of “Based on our findings collectively, we recommend using GSDB on cohorts with slower gait speeds and substantial gait impairments (e.g., proximal femoral fracture). This may be because this algorithm is based on the acceleration norm (overall accelerometry signal rather than a specific axis/direction (e.g., vertical), hence it is more robust to sensor misalignments that are common in unsupervised real-life settings [41]. Moreover, the use of adaptive thresholds, that are derived from the features of a subject’s data and applied to the amplitude of acceleration norm and to step duration for detection of steps belonging to gait sequences, allows increased robustness of the algorithm to irregular and unstable gait patterns”

Assessing real-world gait with digital technology? Validation, insights and recommendations from the Mobilise-D consortium

Background Although digital mobility outcomes (DMOs) can be readily calculated from real-world data collected with wearable devices and ad-hoc algorithms, technical validation is still required. The aim of this paper is to comparatively assess and validate DMOs estimated using real-world gait data from six different cohorts, focusing on gait sequence detection, foot initial contact detection (ICD), cadence (CAD) and stride length (SL) estimates. Methods Twenty healthy older adults, 20 people with Parkinson’s disease, 20 with multiple sclerosis, 19 with proximal femoral fracture, 17 with chronic obstructive pulmonary disease and 12 with congestive heart failure were monitored for 2.5 h in the real-world, using a single wearable device worn on the lower back. A reference system combining inertial modules with distance sensors and pressure insoles was used for comparison of DMOs from the single wearable device. We assessed and validated three algorithms for gait sequence detection, four for ICD, three for CAD and four for SL by concurrently comparing their performances (e.g., accuracy, specificity, sensitivity, absolute and relative errors). Additionally, the effects of walking bout (WB) speed and duration on algorithm performance were investigated. Results We identified two cohort-specific top performing algorithms for gait sequence detection and CAD, and a single best for ICD and SL. Best gait sequence detection algorithms showed good performances (sensitivity > 0.73, positive predictive values > 0.75, specificity > 0.95, accuracy > 0.94). ICD and CAD algorithms presented excellent results, with sensitivity > 0.79, positive predictive values > 0.89 and relative errors < 11% for ICD and < 8.5% for CAD. The best identified SL algorithm showed lower performances than other DMOs (absolute error < 0.21 m). Lower performances across all DMOs were found for the cohort with most severe gait impairments (proximal femoral fracture). Algorithms’ performances were lower for short walking bouts; slower gait speeds (< 0.5 m/s) resulted in reduced performance of the CAD and SL algorithms. Conclusions Overall, the identified algorithms enabled a robust estimation of key DMOs. Our findings showed that the choice of algorithm for estimation of gait sequence detection and CAD should be cohort-specific (e.g., slow walkers and with gait impairments). Short walking bout length and slow walking speed worsened algorithms’ performances