Effect of inspiratory rise time on sputum movement during ventilator hyperinflation in a test lung model

OBJECTIVES: Physiotherapists may use ventilator hyperinflation to enhance secretion clearance for intubated patients. This study investigated the effects of altering percentage inspiratory rise time (IRT) on sputum movement, ratio of peak inspiratory to expiratory flow rate (PIF:PEF ratio) and net peak expiratory flow (PEF) during ventilator hyperinflation in a test lung model. DESIGN: Laboratory-based bench study. INTERVENTIONS: Simulated sputum (two viscosities) was inserted into clean, clear tubing and connected between a ventilator and a resuscitation bag. Thirty-six ventilator hyperinflation breaths were applied for each 5% incremental increase in IRT between 0% and 20%. MAIN OUTCOME MEASURES: The primary outcome was sputum displacement (cm). Secondary outcomes included PIF:PEF ratio and net PEF. RESULTS: Significant cephalad sputum movement of 2.42cm (1.59 to 3.94) occurred with IRT between 5% and 20%, compared with caudad movement of 0.53 cm (0.31 to 1.53) at 0% IRT (median sputum movement difference 3.7cm, 95% confidence interval 2.2 to 4.8, P<0.001). Incremental increases in IRT percentage produced linear enhancements in PIF:PEF ratio and net PEF for both sputum concentrations (P<0.001). However, once the critical threshold for PIF:PEF ratio of 0.9 was achieved, the distance of sputum movement remained consistent for all IRT values exceeding 5%. CONCLUSIONS: Significant increases in sputum movement occurred when IRT percentage was lengthened to achieve the optimal PIF:PEF ratio, irrespective of sputum viscosity. This provides a theoretical rationale for therapists to consider this technique when treating mechanically ventilated patients. As no additional sputum movement was seen beyond the critical PIF:PEF ratio threshold, a low IRT percentage may potentially be used to achieve effective sputum movement

A Comparison of the Accuracy and Reliability of the Wahoo KICKR and SRM Power Meter

The Wahoo KICKR cycling trainer is a new direct-drive electromagnetically braked bike-trainer that allows cyclists to use their own bicycles as ergometer. It is purported to provide ±3% accuracy in power, despite costing considerably less than other cycling ergometers. The purpose of this study was to assess the accuracy and reliability of several KICKR units against the more established SRM power meter using a first-principles based dynamic calibration rig (CALRIG).Five KICKRs and one SRM unit were assessed by a CALRIG-driven incremental test. Following a 15 min warm-up and ‘calibration’ as per manufacturer instructions, power was increased (starting at 50 W) by 50 W every 2 min up to 400 W. Each unit was tested twice non-consecutively, in random order. Data was recorded at 1 Hz, with the last 10 s of each stage being averaged for analysis. The mean error (%) and coefficient of determination (R2) versus CALRIG; as well as the change in mean error and Typical Error of Measurement (TEM) (expressed as a % coefficient of variation) between trials was calculated for each device.The mean error across all KICKR units was -1.5% (range: -3.1% to 0.0%) compared to -1.6% reported by the SRM. R2 >0.999 was found for all KICKR units and SRM compared to the CALRIG. The mean TEM for the KICKRs was 1.5% (range: 1.1% to 1.9%), whereas the SRM reported 0.7%. For test-retest reproducibility, two KICKRs had statistically significant changes in mean error, with an average 1.3% change across all KICKRs. Comparatively, the SRM reported a 0.4% change between trials. The Wahoo KICKR trainer measures power to a similar level of accuracy to the more reputable SRM power meter during an incremental exercise test. Although not as reproducible, the KICKR still demonstrates an acceptable level of reliability for assessing cycling performance

A Gravitational Tractor for Towing Asteroids

We present a concept for a spacecraft that can controllably alter the trajectory of an Earth threatening asteroid using gravity as a towline. The spacecraft hovers near the asteroid with thrusters angled outward so the exhaust does not impinge on the surface. This deflection method is insensitive to the structure, surface properties, and rotation state of the asteroid.Comment: 4 pages, 1 figure - to be published in Natur

The influence of the atmospheric boundary layer on nocturnal layers of noctuids and other moths migrating over southern Britain

Insects migrating at high altitude over southern Britain have been continuously monitored by automatically-operating, vertical-looking radars over a period of several years. During some occasions in the summer months, the migrants were observed to form well-defined layer concentrations, typically at heights of 200-400 m, in the stable night-time atmosphere. Under these conditions, insects are likely to have control over their vertical movements and are selecting flight heights which are favourable for long-range migration. We therefore investigated the factors influencing the formation of these insect layers by comparing radar measurements of the vertical distribution of insect density with meteorological profiles generated by the UK Met. Office’s Unified Model (UM). Radar-derived measurements of mass and displacement speed, along with data from Rothamsted Insect Survey light traps provided information on the identity of the migrants. We present here three case studies where noctuid and pyralid moths contributed substantially to the observed layers. The major meteorological factors influencing the layer concentrations appeared to be: (a) the altitude of the warmest air, (b) heights corresponding to temperature preferences or thresholds for sustained migration and (c), on nights when air temperatures are relatively high, wind-speed maxima associated with the nocturnal jet. Back-trajectories indicated that layer duration may have been determined by the distance to the coast. Overall, the unique combination of meteorological data from the UM and insect data from entomological radar described here show considerable promise for systematic studies of high-altitude insect layering

Desiderata for the development of next-generation electronic health record phenotype libraries

Background High-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In this work, we present a set of desiderata for the design of a next-generation phenotype library that is able to ensure the quality of hosted definitions by combining the functionality currently offered by disparate tooling. Methods A group of researchers examined work to date on phenotype models, implementation, and validation, as well as contemporary phenotype libraries developed as a part of their own phenomics communities. Existing phenotype frameworks were also examined. This work was translated and refined by all the authors into a set of best practices. Results We present 14 library desiderata that promote high-quality phenotype definitions, in the areas of modelling, logging, validation, and sharing and warehousing. Conclusions There are a number of choices to be made when constructing phenotype libraries. Our considerations distil the best practices in the field and include pointers towards their further development to support portable, reproducible, and clinically valid phenotype design. The provision of high-quality phenotype definitions enables electronic health record data to be more effectively used in medical domains

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Bacterial membrane vesicles transport their DNA cargo into host cells

© 2017 The Author(s). Bacterial outer membrane vesicles (OMVs) are extracellular sacs containing biologically active products, such as proteins, cell wall components and toxins. OMVs are reported to contain DNA, however, little is known about the nature of this DNA, nor whether it can be transported into host cells. Our work demonstrates that chromosomal DNA is packaged into OMVs shed by bacteria during exponential phase. Most of this DNA was present on the external surfaces of OMVs, with smaller amounts located internally. The DNA within the internal compartments of Pseudomonas aeruginosa OMVs were consistently enriched in specific regions of the bacterial chromosome, encoding proteins involved in virulence, stress response, antibiotic resistance and metabolism. Furthermore, we demonstrated that OMVs carry DNA into eukaryotic cells, and this DNA was detectable by PCR in the nuclear fraction of cells. These findings suggest a role for OMV-associated DNA in bacterial-host cell interactions and have implications for OMV-based vaccines

Compensatory ingestion upon dietary restriction in Drosophila melanogaster

Dietary restriction extends the lifespan of numerous, evolutionarily diverse species. In D. melanogaster, a prominent model for research on the interaction between nutrition and longevity, dietary restriction is typically based on medium dilution, with possible compensatory ingestion commonly being neglected. Possible problems with this approach are revealed by using a method for direct monitoring of D. melanogaster feeding behavior. This demonstrates that dietary restriction elicits robust compensatory changes in food consumption. As a result, the effect of medium dilution is overestimated and, in certain cases, even fully compensated for. Our results strongly indicate that feeding behavior and nutritional composition act concertedly to determine fly lifespan. Feeding behavior thus emerges as a central element in D. melanogaster aging

‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological ‘gasotransmitter’, in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release. Here, we investigate the basis of its potent antibacterial activity against Escherichia coli and demonstrate, using three globin CO sensors, that CORM-2 releases negligible CO (<0.1 mol CO per mol CORM-2). A strong negative correlation between viability and cellular ruthenium accumulation implies that ruthenium toxicity underlies biocidal activity. Exogenous amino acids and thiols (especially cysteine, glutathione and N-acetyl cysteine) protected bacteria against inhibition of growth by CORM-2. Bacteria treated with 30 μM CORM-2, with added cysteine and histidine, exhibited no significant loss of viability, but were killed in the absence of these amino acids. Their prevention of toxicity correlates with their CORM-2-binding affinities (Cys, Kd 3 μM; His, Kd 130 μM) as determined by 1H-NMR. Glutathione is proposed to be an important intracellular target of CORM-2, with CORM-2 having a much higher affinity for reduced glutathione (GSH) than oxidised glutathione (GSSG) (GSH, Kd 2 μM; GSSG, Kd 25,000 μM). The toxicity of low, but potent, levels (15 μM) of CORM-2 was accompanied by cell lysis, as judged by the release of cytoplasmic ATP pools. The biological effects of CORM-2 and related CORMs, and the design of biological experiments, must be re-examined in the light of these data