Methodology and reliability of respiratory muscle assessment

The optimal method for respiratory muscle endurance (RME) assessment remains unclear. This study assessed the test-retest reliability of two RME-test methodologies. Fifteen healthy adults attended the laboratory on four occasions, separated by 5 ± 2 days, and completed each test in a random, “one on two” order. They performed spirometry testing, maximal respiratory pressure assessment and two different RME tests: an inspiratory resistive breathing (IRB) and an isocapnic hyperpnea endurance (IHE) test. Typical error, expressed as coefficient of variation, for IRB maximal inspiratory pressure (MIP) and IHE maximal ventilation were 12.21 (8.85–19.67) % and 10.73 (7.78–17.29) %, respectively. Intraclass correlation coefficients for the same parameters were 0.83 (0.46-0.94) and 0.80 (0.41-0.93), respectively. No correlations were found between RME parameters derived from the IHE and IRB tests (all p > 0.05). Significant positive correlations were found between both IRB and IHE outcomes and spirometry parameters, MIP and maximal expiratory pressure (p < 0.05).Given these results, IRB and IHE appear to be suitable for RME testing in healthy people, although they may reflect different physiological mechanisms (respiratory mechanics and respiratory muscle capacity for IHE test vs. inspiratory muscle capacity for IRB test). Future studies are therefore warranted that compare IRB and IHE tests in clinical settings

Collapse of a semiflexible polymer in poor solvent

We investigate the dynamics and the pathways of the collapse of a single, semiflexible polymer in a poor solvent via 3-D Brownian Dynamics simulations. Earlier work indicates that the condensation of semiflexible polymers generically proceeds via a cascade through metastable racquet-shaped, long-lived intermediates towards the stable torus state. We investigate the rate of decay of uncollapsed states, analyze the preferential pathways of condensation, and describe likelihood and lifespan of the different metastable states. The simulation are performed with a bead-stiff spring model with excluded volume interaction and exponentially decaying attractive potential. The semiflexible chain collapse is studied as functions of the three relevant length scales of the phenomenon, i.e., the total chain length $L$, the persistence length $L_p$ and the condensation length $L_0 = \sqrt{k_B T L_p/u_0}$, where $u_0$ is a measure of the attractive potential per unit length. Two dimensionless ratios, $L/L_p$ and $L_0/L_p$, suffice to describe the decay rate of uncollapsed states, which appears to scale as $(L/L_p)^{1/3} (L_0/L_p)$. The condensation sequence is described in terms of the time series of the well separated energy levels associated with each metastable collapsed state. The collapsed states are described quantitatively through the spatial correlation of tangent vectors along the chain. We also compare the results obtained with a locally inextensible bead-rod chain and with a phantom bead-spring model. Finally, we show preliminary results on the effects of steady shear flow on the kinetics of collapse.Comment: 9 pages, 8 figure

Adaptation of Left Ventricular Twist Mechanics in Exercise-Trained Children Is Only Evident after the Adolescent Growth Spurt.

The extent of structural cardiac remodeling in response to endurance training is maturity dependent. In adults, this structural adaptation is often associated with the adaptation of left ventricular (LV) twist mechanics. For example, an increase in LV twist often follows an expansion in end-diastolic volume, whereas a reduction in twist may follow a thickening of the LV walls. While structural cardiac remodeling has been shown to be more prominent post-peak height velocity (PHV), it remains to be determined how this maturation-dependent structural remodeling influences LV twist. Therefore, we aimed to (1) compare LV twist mechanics between trained and untrained children pre- and post-PHV and (2) investigate how LV structural variables relate to LV twist mechanics pre- and post-PHV. Left ventricular function and morphology were assessed (echocardiography) in endurance-trained and untrained boys (n = 38 and n = 28, respectively) and girls (n = 39 and n = 34, respectively). Participants were categorized as either pre- or post-PHV using maturity offset to estimate somatic maturation. Pre-PHV, there were no differences in LV twist or torsion between trained and untrained boys (twist: P = .630; torsion: P = .382) or girls (twist: P = .502; torsion: P = .316), and LV twist mechanics were not related with any LV structural variables (P &gt; .05). Post-PHV, LV twist was lower in trained versus untrained boys (P = .004), with torsion lower in trained groups, irrespective of sex (boys: P &lt; .001; girls: P = .017). Moreover, LV torsion was inversely related to LV mass (boys: r = -0.55, P = .001; girls: r = -0.46, P = .003) and end-diastolic volume (boys: r = -0.64, P &lt; .001; girls: r = -0.36, P = .025) in both sexes. A difference in LV twist mechanics between endurance-trained and untrained cohorts is only apparent post-PHV, where structural and functional remodeling were related

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Crystal fields and conduction electrons in praseodymium

The interactions between the crystal-field excitations, the phonons and the conduction electrons in Pr have been studied further. The low-energy satellites to the crystal-field excitations, which are believed to be associated with propagating paramagnon modes in the conduction-electron gas, appear to be quenched by a magnetic field, which also induces a strong hybridization with the phonons