Pentamidine Dosage: A Base/Salt Confusion

Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past decades and show the confusion in the calculation of the dosage of pentamidine in these guidelines and the subsequent published reports on clinical trials and reviews. At present, only pentamidine isethionate is available, but the advised dosage for HAT and leishmaniasis is (historically) based on the amount of pentamidine base. In the treatment of leishmaniasis this is probably resulting in a subtherapeutic treatment. There is thus a need for a new, more transparent and concise guideline concerning the dosage of pentamidine, at least in the treatment of HAT and leishmaniasi

Hybrid Wing Body Aircraft Acoustic Test Preparations and Facility Upgrades

NASA is investigating the potential of acoustic shielding as a means to reduce the noise footprint at airport communities. A subsonic transport aircraft and Langley's 14- by 22-foot Subsonic Wind Tunnel were chosen to test the proposed "low noise" technology. The present experiment studies the basic components of propulsion-airframe shielding in a representative flow regime. To this end, a 5.8-percent scale hybrid wing body model was built with dual state-of-the-art engine noise simulators. The results will provide benchmark shielding data and key hybrid wing body aircraft noise data. The test matrix for the experiment contains both aerodynamic and acoustic test configurations, broadband turbomachinery and hot jet engine noise simulators, and various airframe configurations which include landing gear, cruise and drooped wing leading edges, trailing edge elevons and vertical tail options. To aid in this study, two major facility upgrades have occurred. First, a propane delivery system has been installed to provide the acoustic characteristics with realistic temperature conditions for a hot gas engine; and second, a traversing microphone array and side towers have been added to gain full spectral and directivity noise characteristics

Development of a Microphone Phased Array Capability for the Langley 14- by 22-Foot Subsonic Tunnel

A new aeroacoustic measurement capability has been developed for use in open-jet testing in the NASA Langley 14- by 22-Foot Subsonic Tunnel (14x22 tunnel). A suite of instruments has been developed to characterize noise source strengths, locations, and directivity for both semi-span and full-span test articles in the facility. The primary instrument of the suite is a fully traversable microphone phased array for identification of noise source locations and strengths on models. The array can be mounted in the ceiling or on either side of the facility test section to accommodate various test article configurations. Complementing the phased array is an ensemble of streamwise traversing microphones that can be placed around the test section at defined locations to conduct noise source directivity studies along both flyover and sideline axes. A customized data acquisition system has been developed for the instrumentation suite that allows for command and control of all aspects of the array and microphone hardware, and is coupled with a comprehensive data reduction system to generate information in near real time. This information includes such items as time histories and spectral data for individual microphones and groups of microphones, contour presentations of noise source locations and strengths, and hemispherical directivity data. The data acquisition system integrates with the 14x22 tunnel data system to allow real time capture of facility parameters during acquisition of microphone data. The design of the phased array system has been vetted via a theoretical performance analysis based on conventional monopole beamforming and DAMAS deconvolution. The performance analysis provides the ability to compute figures of merit for the array as well as characterize factors such as beamwidths, sidelobe levels, and source discrimination for the types of noise sources anticipated in the 14x22 tunnel. The full paper will summarize in detail the design of the instrumentation suite, the construction of the hardware system, and the results of the performance analysis. Although the instrumentation suite is designed to characterize noise for a variety of test articles in the 14x22 tunnel, this paper will concentrate on description of the instruments for two specific test campaigns in the facility, namely a full-span NASA Hybrid Wing Body (HWB) model entry and a semi-span Gulfstream aircraft model entry, tested in the facility in the winter of 2012 and spring of 2013, respectively

Neuromuscular training improves movement competency and physical performance measures in 11-13 year old female netball athletes

The purpose of this study was to examine the effects of a neuromuscular training program on movement competency and measures of physical performance in youth female netball players. It was hypothesized that significant improvements would be found in movement competency and physical performance measures following the intervention. Twenty-three junior female netball players (age, 12.17 ± 0.94 yrs; height, 1.63 ± 0.08 m; weight, 51.81 ± 8.45 kg) completed a test battery before and after a six-week training intervention. 13 of these athletes underwent six weeks of neuromuscular training, which incorporated plyometrics and resistance training. Trained athletes showed significant improvements in 20 m sprint time, 505 agility time, countermovement jump height and peak power (p ≤ 0.05, g \u3e 0.8). Additionally, trained athletes significantly improved their score in the Netball Movement Screening Tool (NMST) (p \u3c 0.05, g \u3e -1.30); while the athletes also demonstrated increased reach in the anterior and posteromedial directions for the right and left leg, and in the posterolateral direction for the left leg only in the Star Excursion Balance Test (SEBT) (p \u3c 0.05, g \u3e -0.03). Control subjects did not exhibit any significant changes during the 6-week period. Significant negative correlations were found between improved score on the NMST and decreased 5 m, 10 m and 20 m sprint time, and 505 change of direction time (r \u3e 0.4, p ≤ 0.05). Results of the study affirm the hypothesis that a six-week neuromuscular training intervention can improve performance and movement competency in youth netball player

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

The relationship between physical and wellness measures and injury in amateur rugby union players

peer-reviewedObjectives To investigate factors associated with injury in amateur male and female rugby union players. Design A prospective cohort study. Setting Amateur rugby clubs in Ireland. Participants Male (n = 113) and female (n = 24) amateur rugby union players from 5 of the top 58 amateur clubs in Ireland. Main outcome measures Pre-season testing included physical tests assessing hamstring flexibility, dorsiflexion range of movement, adductor muscle strength and foot position. Wellness questionnaires assessed sleep quality (PSQI), coping skills (ACSI-28) and support levels (PASS-Q). Players were monitored throughout the season for injury. Results The time-loss match injury incidence rate was 48.2/1000 player hours for males and 45.2/1000 player hours for females. Two risk profiles emerged involving; ‘age + navicular drop + training pitch surface’ (53%) and ‘age + navicular drop + groin strength’ (16%). An inverse relationship between groin strength and groin injury was found for the ‘backs’ players (−0.307, p < 0.05). Using the PSQI, 61% of players had poor sleep quality, however no relationship between the wellness questionnaires and injury was found. Conclusion Two injury risk profiles emerged, associated with subsequent injury occurrence. Using these risk profiles, individualized prevention strategies may be designed regarding deficits in groin muscle strength and identifying foot alignment.ACCEPTEDpeer-reviewe

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting