The detection and sensory perception of inspiratory resistive loads in people with chronic tetraplegia

This study investigated sensations of breathing following tetraplegia. Fifteen people with chronic tetraplegia and fifteen healthy able-bodied controls matched for age, sex, height, and weight participated. Sensations of breathing were quantified by determining the threshold for detecting an added resistance during inspiration. In a separate task, the perceived magnitudes of six suprathreshold resistive loads were determined with a modified Borg scale. The detection threshold of 0.34 cmH2O/L/s [standard deviation (SD) 0.14] in the tetraplegia group was higher than the 0.23 cmH2O/L/s (SD 0.10) threshold for able-bodied controls (P = 0.004). Both participant groups perceived larger loads to be more effortful, with the Borg effort rating increasing linearly with the peak inspiratory pressure generated at each load. The relationship between Borg effort rating and peak inspiratory pressure was steeper in participants with tetraplegia than in able-bodied controls (P = 0.001), but there was no difference when pressure was divided by maximal inspiratory pressure (P = 0.95). Despite a higher detection threshold, the findings suggest that the perceived magnitude of a suprathreshold inspiratory load is not impaired in chronic tetraplegia and that load magnitude perception is related to the maximal, and not absolute, inspiratory muscle force. NEW & NOTEWORTHY Sensations of breathing are thought to be impaired following chronic tetraplegia. The detection threshold for an added resistive load during inspiration was higher in people with tetraplegia than in healthy able-bodied participants. However, for inspiratory loads above the detection threshold, the perceived magnitude of a resistive load as a function of the peak inspiratory pressure was greater in tetraplegia. Load magnitude perception was comparable between participant groups when peak pressure was divided by maximal inspiratory pressure

The reliability of inspiratory resistive load magnitude and detection testing

Objectives: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. Design: Cohort of convenience. Setting: Respiratory physiology laboratory. Participants: Twenty healthy adults. Interventions: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome Measures: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. Results: ICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. Conclusions: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease

A pragmatic evidence-based approach to post-mortem perinatal imaging

Post-mortem imaging has a high acceptance rate amongst parents and healthcare professionals as a non-invasive method for investigating perinatal deaths. Previously viewed as a 'niche' subspecialty, it is becoming increasingly requested, with general radiologists now more frequently asked to oversee and advise on appropriate imaging protocols. Much of the current literature to date has focussed on diagnostic accuracy and clinical experiences of individual centres and their imaging techniques (e.g. post-mortem CT, MRI, ultrasound and micro-CT), and pragmatic, evidence-based guidance for how to approach such referrals in real-world practice is lacking. In this review, we summarise the latest research and provide an approach and flowchart to aid decision-making for perinatal post-mortem imaging. We highlight key aspects of the maternal and antenatal history that radiologists should consider when protocolling studies (e.g. antenatal imaging findings and history), and emphasise important factors that could impact the diagnostic quality of post-mortem imaging examinations (e.g. post-mortem weight and time interval). Considerations regarding when ancillary post-mortem image-guided biopsy tests are beneficial are also addressed, and we provide key references for imaging protocols for a variety of cross-sectional imaging modalities

Development of the Knowledge of Genome Sequencing (KOGS) questionnaire

OBJECTIVE: Whole-genome sequencing is being implemented in research and clinical care, yet tools to assess patients' knowledge are lacking. Our aim was to develop a robust measure of whole-genome sequencing knowledge suitable for patients and other stakeholders including research participants, public, students, and healthcare professionals. METHODS: An initial set of 17 items was developed via an iterative process including literature review, expert consultation, focus groups, and cognitive interviews with patients, and then administered to 243 individuals. We used exploratory factor analysis and item-response theory to confirm the psychometric suitability of the candidate items for assessing whole-genome sequencing knowledge. RESULTS: There was a strong main component after removing 5 items with low factor loadings. Item and scale homogeneity was achieved using Mokken scale analysis. Three further items were removed because they were misfits, inverse duplicates or resulted in local dependency. The remaining nine items fitted the two-parameter logistic IRT model which achieved excellent fit to the observed data. Cronbach's alpha was 0.79 indicating acceptable reliability. CONCLUSION: The KOGS, developed using a rigorous psychometric approach, is a brief and reliable tool. PRACTICE IMPLICATIONS: The KOGS may prove useful for researchers and healthcare professionals using whole-genome sequencing with patients and other stakeholders

Young people's understanding, attitudes and involvement in decision-making about genome sequencing for rare diseases: A qualitative study with participants in the UK 100,000 genomes project

Genome sequencing (GS) will have a profound impact on the diagnosis of rare and inherited diseases in children and young people. We conducted 27 semi-structured interviews with young people aged 11-19 having GS through the UK 100,000 Genomes Project. Participants demonstrated an understanding of the role and function of genes and DNA, however the terms 'genome' and 'genome sequencing' were less well understood. Participants were primarily motivated to take part to get a diagnosis or identify the gene causing their condition. The majority of participants understood they might not receive a diagnostic result. Most were unconcerned about data security or access, however anxieties existed around what the results might show and the potential for disappointment if the result was negative. Signing an assent form empowered young people, formalised the process and instilled a sense of responsibility for their choice to participate. Most young people (≥16 years) had consented to receive secondary findings and had come to that decision without parental influence. Our research suggests that at least some young people are capable of making informed decisions about taking part in GS, and that involving them in discussions about testing can empower them to take responsibility over healthcare decisions that affect them

Impact of respiratory muscle training on respiratory muscle strength, respiratory function and quality of life in individuals with tetraplegia: A randomised clinical trial

Background Respiratory complications remain a leading cause of morbidity and mortality in people with acute and chronic tetraplegia. Respiratory muscle weakness following spinal cord injury-induced tetraplegia impairs lung function and the ability to cough. In particular, inspiratory muscle strength has been identified as the best predictor of the likelihood of developing pneumonia in individuals with tetraplegia. We hypothesised that 6 weeks of progressive respiratory muscle training (RMT) increases respiratory muscle strength with improvements in lung function, quality of life and respiratory health. Methods Sixty-two adults with tetraplegia participated in a double-blind randomised controlled trial. Active or sham RMT was performed twice daily for 6 weeks. Inspiratory muscle strength, measured as maximal inspiratory pressure (PImax) was the primary outcome. Secondary outcomes included lung function, quality of life and respiratory health. Between-group comparisons were obtained with linear models adjusting for baseline values of the outcomes. Results After 6 weeks, there was a greater improvement in PImax in the active group than in the sham group (mean difference 11.5 cmH 2 O (95% CI 5.6 to 17.4), p<0.001) and respiratory symptoms were reduced (St George Respiratory Questionnaire mean difference 10.3 points (0.01-20.65), p=0.046). Significant improvements were observed in quality of life (EuroQol-Five Dimensional Visual Analogue Scale 14.9 points (1.9-27.9), p=0.023) and perceived breathlessness (Borg score 0.64 (0.11-1.17), p=0.021). There were no significant improvements in other measures of respiratory function (p=0.126-0.979). Conclusions Progressive RMT increases inspiratory muscle strength in people with tetraplegia, by a magnitude which is likely to be clinically significant. Measurement of baseline PImax and provision of RMT to at-risk individuals may reduce respiratory complications after tetraplegia. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808)

Remarks on the method of comparison equations (generalized WKB method) and the generalized Ermakov-Pinney equation

The connection between the method of comparison equations (generalized WKB method) and the Ermakov-Pinney equation is established. A perturbative scheme of solution of the generalized Ermakov-Pinney equation is developed and is applied to the construction of perturbative series for second-order differential equations with and without turning points.Comment: The collective of the authors is enlarged and the calculations in Sec. 3 are correcte

Flexible, actin-based ridges colocalise with the β1 integrin on the surface of melanoma cells

Using a combination of laser-scanning confocal microscopy and atomic force microscopy, we have identified flexible, actin-based structures on the surface of cells derived from the vertical growth phase of melanoma progression. These flexible structures, lacking on the surface of mature melanocytes, were observed on the surface of all four melanoma cell lines tested. Further investigation revealed that the β1 integrin colocalises with these actin-based ridges on the cell surface, whereas β1 integrin distribution in melanocytes did not correlate with actin-based structures. Fibronectin staining on the surface of melanoma cells was partially codistributed with the ridges. The combination of structural information derived from atomic force microscopy images and fluorescent imaging of the distribution of labelled proteins involved in invasion and metastasis has allowed us to identify a common feature that may be involved in disease progression, at the surface of vertical growth phase melanoma cells, despite the known variation in genetic composition of melanoma

Decision-making, attitudes, and understanding among patients and relatives invited to undergo genome sequencing in the 100,000 Genomes Project: A multisite survey study

PURPOSE: The purpose of this study was to assess decisions, attitudes, and understanding of participants (patients, parents, relatives) having genome sequencing for rare disease diagnosis. METHODS: This study involved a cross-sectional observational survey with participants in the 100,000 Genomes Project. RESULTS: Survey response rate was 51% (504/978). Most participants self-reported that they had decided to undergo genome sequencing (94%) and that this was an informed decision (84%) with low decisional conflict (95%). Most self-reported that they had chosen to receive additional findings (88%) and that this was an informed decision (89%) with low decisional conflict (95%). Participants were motivated more by the desire to help others via research than by the belief it would help them obtain a diagnosis (Z = 14.23, P = 5.75 × 10-46), although both motivations were high. Concerns were relatively few but, where expressed, were more about the potential psychological impact of results than data sharing/access (Z = 9.61, P = 7.65 × 10-22). Concerns were higher among male, Asian or Asian British, and more religious participants. General and context-specific understanding of genome sequencing were both moderately high (means 5.2/9.0 and 22.5/28.0, respectively). CONCLUSION: These findings are useful to inform consent guidelines and clinical implementation of genome sequencing