Functional imaging for assessing regional lung ventilation in preclinical and clinical research

Dynamic heterogeneity in lung ventilation is an important measure of pulmonary function and may be characteristic of early pulmonary disease. While standard indices like spirometry, body plethysmography, and blood gases have been utilized to assess lung function, they do not provide adequate information on regional ventilatory distribution nor function assessments of ventilation during the respiratory cycle. Emerging technologies such as xenon CT, volumetric CT, functional MRI and X-ray velocimetry can assess regional ventilation using non-invasive radiographic methods that may complement current methods of assessing lung function. As a supplement to current modalities of pulmonary function assessment, functional lung imaging has the potential to identify respiratory disease phenotypes with distinct natural histories. Moreover, these novel technologies may offer an optimal strategy to evaluate the effectiveness of novel therapies and therapies targeting localized small airways disease in preclinical and clinical research. In this review, we aim to discuss the features of functional lung imaging, as well as its potential application and limitations to adoption in research.</p

Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed “element-specific” P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed

Determining the Surface Tension of Microliter Amounts of Liquid

We describe a method for determining the surface tension of liquids by measuring the pull-off force between curved surfaces with a bridging droplet. The technique is useful for cases when only very small amounts of liquid are available, as in medical an

Decrement of the skin conductance response to repeated volitional inspiration

Objective. To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172–80]. Methods. Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20 s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. Results. Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P<0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P<0.001) and 14.4% (95% CI (0.104, 0.200), P<0.001) of the first run amplitude. Conclusions. Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. Significance. The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy

Effect of Acute Intermittent CPAP Depressurization during Sleep in Obese Patients.

Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic (11.1 ± 0.6 cm H20) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.8/9 subjects tolerated CPAP withdrawal. The average AHI during CPAP-on and CPAP-off periods was 3.6 ± 0.6 and 15.8 ± 3.6 respectively (p<0.05). The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP