Measurement of Cough Aerodynamics in Healthy Adults.

ImportanceCough is a critical human reflex and also among the most frequent symptoms in medicine. Despite the prevalence of disordered cough in laryngeal pathologies, comprehensive and quantitative evaluation of cough in these patients is lacking.ObjectiveHerein we seek to establish normative values for cough aerodynamics to provide a population standard for reference in future studies.Design, setting, and participantsHealthy subjects were recruited from an outpatient clinic to perform voluntary cough. Subjects were instructed on the technique for maximal voluntary cough production with measurements recorded on pneumotachograph. Fifty-two subjects were studied, including 29 women and 23 men with a mean age of 51.6 and 52.3 years, respectively. Main Outcomes and Measures: Cough peak airflow, peak pressure, and expiratory rise time. Results were stratified by age, gender, and height.ResultsPeak airflow demonstrated significant differences across age, gender, and height, with flow increasing according to increasing height. Peak cough pressure also increased with height and was significantly greater in males versus females. Expiratory rise time, the time from glottal opening to peak airflow, did not vary with age or height but was statistically significantly longer in women.ConclusionsCough aerodynamics can be readily measured objectively in the outpatient setting. Expiratory rise time, peak flow, and peak pressure are important aspects of each cough epoch. Normative data provided herein can be used for future studies of patients with laryngotracheal disorders, and these cough parameters may prove to be simple, accessible, and repeatable outcome measures

Changes in Lifeguards’ Hazard Detection and Eye Movements with Experience: Is One Season Enough?

Surveillance is key to the lifesaving capability of lifeguards. Experienced personnel consistently display enhanced hazard detection capabilities compared to less experienced counterparts. However, the mechanisms which underpin this effect and the time it takes to develop these skills are not understood. We hypothesized that, after one season of experience, the number of hazards detected by, and eye movements of, less experienced lifeguards (LEL) would more closely approximate experienced lifeguards (EL). The LEL watched ‘beach scene’ videos at the beginning and end of their first season. The number of hazards detected and eye-movement data were collected and compared to the EL group. The LEL perceived fewer hazards than EL and did not increase over the season. There was no difference in eye-movements between groups. Findings suggest one season is not enough for lifeguards to develop enhanced hazard detection skills and skill level differences are not underpinned by differences in gaze behavior

Abelson Phosphorylation of CLASP2 Modulates its Association With Microtubules and Actin

The Abelson (Abl) non-receptor tyrosine kinase regulates the cytoskeleton during multiple stages of neural development, from neurulation, to the articulation of axons and dendrites, to synapse formation and maintenance. We previously showed that Abl is genetically linked to the microtubule (MT) plus end tracking protein (+TIP) CLASP in Drosophila. Here we show in vertebrate cells that Abl binds to CLASP and phosphorylates it in response to serum or PDGF stimulation. In vitro, Abl phosphorylates CLASP with a Km of 1.89 µM, indicating that CLASP is a bona fide substrate. Abl-phosphorylated tyrosine residues that we detect in CLASP by mass spectrometry lie within previously mapped F-actin and MT plus end interaction domains. Using purified proteins, we find that Abl phosphorylation modulates direct binding between purified CLASP2 with both MTs and actin. Consistent with these observations, Abl-induced phosphorylation of CLASP2 modulates its localization as well as the distribution of F-actin structures in spinal cord growth cones. Our data suggest that the functional relationship between Abl and CLASP2 is conserved and provides a means to control the CLASP2 association with the cytoskeleton. © 2014 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc

Restriction endonuclease TseI cleaves A:A and T:T mismatches in CAG and CTG repeats.

The type II restriction endonuclease TseI recognizes the DNA target sequence 5'-G^CWGC-3' (where W = A or T) and cleaves after the first G to produce fragments with three-base 5'-overhangs. We have determined that it is a dimeric protein capable of cleaving not only its target sequence but also one containing A:A or T:T mismatches at the central base pair in the target sequence. The cleavage of targets containing these mismatches is as efficient as cleavage of the correct target sequence containing a central A:T base pair. The cleavage mechanism does not apparently use a base flipping mechanism as found for some other type II restriction endonuclease recognizing similarly degenerate target sequences. The ability of TseI to cleave targets with mismatches means that it can cleave the unusual DNA hairpin structures containing A:A or T:T mismatches formed by the repetitive DNA sequences associated with Huntington's disease (CAG repeats) and myotonic dystrophy type 1 (CTG repeats)

Low dose CT vs plain abdominal radiography for the investigation of the acute abdomen

Background: To compare low-dose abdominal computed tomography (LDCT) with plain abdominal radiography (AR) in the primary investigation of acute abdominal pain to determine if there is a difference in diagnostic yield, the number of additional investigations required and hospital length of stay (LOS). Methods: This randomized controlled trial was approved by the institutional review board, and informed consent was obtained. Patients presenting to the emergency department with an acute abdomen and who would normally be investigated with AR were randomized to either AR or LDCT. The estimated radiation dose of the LDCT protocol was 2–3 mSv compared to 1.1 mSv for AR. Pearson\u27s chi-square and the independent samples t-test were used for the statistical analysis. Results: A total of 142 patients were eligible, and after exclusions and omitting those with incomplete data, 55 patients remained for analysis in the AR arm and 53 in the LDCT arm. A diagnosis could be obtained in 12 (21.8%) patients investigated with AR compared to 34 (64.2%) for LDCT (P \u3c 0.001). Twenty-eight (50.9%) patients in the AR group required further imaging during their admission compared to 14 (26.4%) in the LDCT group (P= 0.009). There was no difference in the median hospital LOS (3.84 days for AR versus 4.24 days for LDCT, P= 0.83). Conclusion: LDCT demonstrates a superior diagnostic yield over AR and reduces the number of subsequent imaging tests for a minimal cost in radiation exposure. However, there is no difference in the overall hospital LOS between the two imaging strategies

Syk, c-Src, the αvβ3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption

In this study, we establish that the tyrosine kinase Syk is essential for osteoclast function in vitro and in vivo. Syk−/− osteoclasts fail to organize their cytoskeleton, and, as such, their bone-resorptive capacity is arrested. This defect results in increased skeletal mass in Syk−/− embryos and dampened basal and stimulated bone resorption in chimeric mice whose osteoclasts lack the kinase. The skeletal impact of Syk deficiency reflects diminished activity of the mature osteoclast and not impaired differentiation. Syk regulates bone resorption by its inclusion with the αvβ3 integrin and c-Src in a signaling complex, which is generated only when αvβ3 is activated. Upon integrin occupancy, c-Src phosphorylates Syk. αvβ3-induced phosphorylation of Syk and the latter's capacity to associate with c-Src is mediated by the immunoreceptor tyrosine-based activation motif (ITAM) proteins Dap12 and FcRγ. Thus, in conjunction with ITAM-bearing proteins, Syk, c-Src, and αvβ3 represent an essential signaling complex in the bone-resorbing osteoclast, and, therefore, each is a candidate therapeutic target

Dynamical masses and stellar evolutionary model predictions of M stars

Funding: J.P. gratefully acknowledges the support of the National Science Foundation (NSF) Graduate Research Fellowship through grant Nos. DGE1144152 and DGE1745303. K.I.Ö. gratefully acknowledges the support of the Simons Foundation through a Simons Collaboration on the Origins of Life (SCOL) PI grant (No. 321183). G.J.H. is supported by general grant 11773002 awarded by the National Science Foundation of China. L.I.C. gratefully acknowledges support from the David and Lucille Packard Foundation, the Virginia Space Grant Consortium, and Johnson & Johnson’s WiSTEM2D Award. V.V.G. gratefully acknowledges support from FONDECYT Iniciación 11180904. Support for this work was also provided by NASA through the NASA Hubble Fellowship grant Nos. HST-HF2-51460.001-A, HST-HF2-51405.001-A, and HST-HF2-51429.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555.In this era of Gaia and ALMA, dynamical stellar mass measurements, derived from spatially and spectrally resolved observations of the Keplerian rotation of circumstellar disks, provide benchmarks that are independent of observations of stellar characteristics and their uncertainties. These benchmarks can then be used to validate and improve stellar evolutionary models, the latter of which can lead to both imprecise and inaccurate mass predictions for pre-main-sequence, low-mass (≤0.5 M⊙) stars. We present the dynamical stellar masses derived from disks around three M stars (FP Tau, J0432+1827, and J1100-7619) using ALMA observations of 12CO (J = 2-1) and 13CO (J = 2-1) emission. These are the first dynamical stellar mass measurements for J0432+1827 and J1100-7619 (0.192 ± 0.005 M⊙ and 0.461 ± 0.057 M⊙, respectively) and the most precise measurement for FP Tau (0.395 ± 0.012 M⊙). Fiducial stellar evolutionary model tracks, which do not include any treatment of magnetic activity, agree with the dynamical stellar mass measurement of J0432+1827 but underpredict the mass by ∼60% for FP Tau and by ∼80% for J1100-7619. Possible explanations for the underpredictions include inaccurate assumptions of stellar effective temperature, undetected binarity for J1100-7619, and that fiducial stellar evolutionary models are not complex enough to represent these stars. In the former case, the stellar effective temperatures would need to be increased by amounts ranging from ∼40 to ∼340 K to reconcile the fiducial stellar evolutionary model predictions with the dynamically measured masses. In the latter case, we show that the dynamical masses can be reproduced using results from stellar evolutionary models with starspots, which incorporate fractional starspot coverage to represent the manifestation of magnetic activity. Folding in low-mass M stars from the literature and assuming that the stellar effective temperatures are imprecise but accurate, we find tentative evidence of a relationship between fractional starspot coverage and observed effective temperature for these young, cool stars.Publisher PDFPeer reviewe