An overview of the quiet short-haul research aircraft program

An overview of the Quiet Short Haul Research Aircraft (QSRA) Program is presented, with special emphasis on its propulsion and acoustic aspects. A description of the NASA technical participation in the program including wind tunnel testing, engine ground tests, and advanced aircraft simulation is given. The aircraft and its systems are described and, measured performance, where available, is compared to program goals. Preliminary data indicate that additional research and development are needed in some areas of which acoustics is an example. Some of these additional research areas and potential experiments using the QSRA to develop the technology are discussed. The concept of the QSRA as a national flight research facility is explained

Transpleural systemic artery-pulmonary artery communications in the absence of chronic inflammatory lung disease. A case series and review of the literature

AIM: To describe the causes and computed tomography (CT) and angiographic appearances of transpleural systemic artery-pulmonary artery shunts in patients without chronic inflammatory lung disease and determine their best management. MATERIALS AND METHODS: All patients referred to a tertiary referral unit between January 2013 and January 2020 in whom a diagnosis of a systemic-pulmonary artery communication without underlying chronic inflammatory lung disease was subsequently made have been included in this report. Medical records and imaging findings were reviewed retrospectively. RESULTS: Ten patients (male: female ratio = 7:3; median age 42 years [range 22-70 years]) with systemic artery-pulmonary artery shunts without chronic inflammatory lung disease were identified. Five were misdiagnosed as having a pulmonary arteriovenous malformation and had been referred for embolisation. In six patients, there was either a history of accidental or iatrogenic thoracic trauma or of inflammatory disease involving the pleura, and in two patients, in whom a previous medical history could not be obtained, there were CT features suggesting previous pleural inflammatory disease. Two shunts were thought to be congenital. All individuals were asymptomatic other than one with localised thoracic discomfort that dated from the time of surgery. All patients were managed conservatively and have remained well with a median follow-up of 4.5 years (range 1-11.3 years). CONCLUSIONS: Localised transpleural systemic artery-pulmonary artery shunts in the absence of chronic inflammatory lung disease are usually related to previous thoracic trauma/intervention or abdominal or pulmonary sepsis involving a pleural or diaphragmatic surface. Congenital shunts are rare. The present study and much of the literature supports conservative management

Directional Next-Generation RNA Sequencing and Examination of Premature Termination Codon Mutations in Endoglin/Hereditary Haemorrhagic Telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is a disease characterised by abnormal vascular structures, and most commonly caused by mutations in ENG, ACVRL1 or SMAD4 encoding endothelial cell-expressed proteins involved in TGF-β superfamily signalling. The majority of mutations reported on the HHT mutation database are predicted to lead to stop codons, either due to frameshifts or direct nonsense substitutions. The proportion is higher for ENG (67%) and SMAD4 (65%) than for ACVRL1 (42%), p < 0.0001. Here, by focussing on ENG, we report why conventional views of these mutations may need to be revised. Of the 111 stop codon-generating ENG mutations, on ExPASy translation, all except one were premature termination codons (PTCs), sited at least 50-55 bp upstream of the final exon-exon boundary of the main endoglin isoform, L-endoglin. This strongly suggests that the mutated RNA species will undergo nonsense-mediated decay. We provide new in vitro expression data to support dominant negative activity of stable truncated endoglin proteins but suggest these will not generate HHT: the single natural stop codon mutation in L-endoglin (sited within 50-55 nucleotides of the final exon-exon boundary) is unlikely to generate functional protein since it replaces the entire transmembrane domain, as would 8 further natural stop codon mutations, if the minor S-endoglin isoform were implicated in HHT pathogenesis. Finally, next-generation RNA sequencing data of 7 different RNA libraries from primary human endothelial cells demonstrate that multiple intronic regions of ENG are transcribed. The potential consequences of heterozygous deletions or duplications of such regions are discussed. These data support the haploinsufficiency model for HHT pathogenesis, explain why final exon mutations have not been detected to date in HHT, emphasise the potential need for functional examination of non-PTC-generating mutations, and lead to proposals for an alternate stratification system of mutational types for HHT genotype-phenotype correlations

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

The Positional Anthropometric and Performance Profile of Elite Gaelic Football Players.

The aim of the current investigation was to evaluate the variation in the anthropometric and performance characteristics of elite Gaelic football players with respect of position. One hundred and forty-eight elite Gaelic footballers underwent anthropometric (height, body mass, sum of seven skinfolds, % adipose tissue) and performance [counter movement jump height (CMJ), CMJ peak power, CMJ relative peak power, squat jump height (SJ), SJ peak power, SJ relative peak power, 5-, 10- and 20 m sprint times and Yo-Yo Intermittent Recovery Test Level 2 (Yo-YoIRT2)] during 'the early in-season' phase. Data were split into five positional groups (full-back, half-back, midfield, half-forward and full-forward). Higher %AT was observed in full forwards when compared to the half backs (p = 0.001), midfielders (p = 0.035) and half forwards (p = 0.021). Full forwards had significantly greater SJ (p = 0.036) and CMJ (p = 0.013) when compared to the midfielders with no other positional differences observed. No significant variation in sprint times was observed across positions. When Yo-YoIRT2 was considered, full forwards and full backs completed significantly lower distances compared to the middle three positional lines of, half backs, midfielders and half forwards (p = 0.00). The current study is the first to provide normative data for anthropometric and performance values of elite Gaelic football players which in turn can be utilised by coaches to generate appropriate training regimes to maximise position specific preparation for competitive match-play

The UK prevalence of hereditary haemorrhagic telangiectasia and its association with sex, socioeconomic status and region of residence: a population-based study

Background Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of aberrant blood vessel development characterised by arteriovenous malformations. HHT is associated with significant morbidity due to complications including epistaxis, gastrointestinal bleeding and stroke. We explored the hypothesis that a diagnosis of HHT is associated with sex, socioeconomic status and geographical location.Methods We used The Health Improvement Network, a longitudinal, computerised general practice database covering 5% of the UK population to calculate prevalence estimates for HHT stratified by age, sex, socioeconomic status and geographical location.Results The 2010 UK point prevalence for HHT was 1.06/10 000 person years (95% CI 0.95 to 1.17) or 1 in 9400 individuals. The diagnosed prevalence of HHT was significantly higher in women compared with men (adjusted prevalence rate ratio (PRR) 1.53, 95% CI 1.24 to 1.88) and in those from the most affluent socioeconomic group compared with the least (adjusted PRR 1.74, 95% CI 1.14 to 2.64). The PRR varied between different regions of the UK, being highest in the South West and lowest in the West Midlands (adjusted PRR for former compared with latter 1.86, 95% CI 1.61 to 2.15).Conclusions HHT prevalence is more common in the UK population than previously demonstrated, though this updated figure is still likely to be an underestimate. HHT appears to be significantly under-diagnosed in men, which is likely to reflect their lower rates of consultation with primary care services. There is under-diagnosis in patients from lower socioeconomic groups and a marked variation in the prevalence of diagnosis between different geographical regions across the UK that requires further investigation

Hemoglobin Is a Vital Determinant of Arterial Oxygen Content in Hypoxemic Patients with Pulmonary Arteriovenous Malformations.

RATIONALE: Arterial partial pressure of oxygen (PaO2), and oxygen saturation (SaO2) are commonly measured in respiratory practice, but arterial oxygen content (CaO2) refers to the volume of oxygen delivered to the tissues per unit blood volume. CaO2 is calculated from SaO2 and the hemoglobin concentration in blood, recognizing that each gram of hemoglobin can transport approximately 1.34mls of oxygen when fully saturated. OBJECTIVES: To prospectively evaluate serial changes in CaO2 in man, incorporating and excluding dynamic changes to oxygenation and hemoglobin parameters that may occur during life. METHODS: A cohort of 497 consecutive patients at risk of both hypoxemia and anemia were recruited. The patients had radiologically-proven pulmonary arteriovenous malformations (PAVMs) which result in hypoxemia due to right-to-left shunting, and concurrent hereditary hemorrhagic telangiectasia (HHT) which placed them at risk of iron deficiency anemia due to recurrent hemorrhagic iron losses. Presentation SaO2 (breathing room air, by pulse oximetry), hemoglobin, red cell and iron indices were measured, and CaO2 calculated by SaO2*hemoglobin*1.34mls/gram. Serial measurements were evaluated in 100 cases spanning up to 32.1 (median 10.5) years. RESULTS: Presentation CaO2 ranged from 7.6-27.5 (median 17.6) mls/dL. CaO2 did not change appreciably across the SaO2 quartiles. In contrast, hemoglobin ranged from 5.9-21.8g/dL (median 14.1g/dL), with a linear increase in CaO2 across hemoglobin quartiles. Following PAVM embolization and an immediate increase in SaO2, hemoglobin fell and CaO2 was unchanged 1.6-12 (median 4) months later. When hemoglobin fell due to iron deficiency, there was no change in SaO2. Similarly, when hemoglobin rose after iron treatment, there was no change in SaO2, and the expected CaO2 increment was observed. These relationships were not evident during pregnancy when hemoglobin fell, and PAVMs usually deteriorated: In pregnancy SaO2 commonly increased, and serial CaO2 values (incorporating hemodilution/anemia) more accurately reflected deteriorating PAVM status. An apparent fall in CaO2 with age in females was attributable to the development of iron deficiency. There was an unexplained increase in CaO2 with age in males in follow up after embolization. CONCLUSIONS: Hemoglobin/CaO2 should be further incorporated into oxygenation considerations. More attention should be given to modest changes in hemoglobin that substantially modify CaO2

The Performance Effect of Scheduled Carbohydrate and Caffeine Intake during Simulated Team Sport Match-Play

The aim of the current investigation was to identify the effects of scheduled carbohydrate (CHO) and caffeine (CAF) supplementation on simulated team sport match-play performance. Ten male hurling players completed three hurling match-play simulation protocols (HSP) performed 7 days apart in a double-blind, randomized design. Supplementation included CHO, CHO + CAF, and placebo (PLA). In a randomized order, participants ingested either a 6% CHO solution, a PLA solution of similar taste, or a combined intake of 6% CHO solution + 200 mg CAF capsule. At specific time points (Pre-0 min; half time (HT)-30 min; full time (FT)-60 min), participants completed a repeated sprint protocol (RAST; 12 7 20 m). Physiological [% maximal oxygen uptake (%VO2max), % mean oxygen uptake (%VO2mean), % maximal heart rate (%HRmax), % mean heart rate (%HRmean), respiratory exchange ratio (RER), and blood lactate (BLa)] and performance [(best sprint time (RSAbest), mean sprint time (RSAmean), and rate of perceived exertion (RPE)] variables were monitored throughout each simulation. Non-significant differences were observed between supplement trials (CHO, CHO + CAF, and PLA) for BLa (\u3b72 = 0.001, small), %VO2max (\u3b72 = 0.001, small), %VO2mean (\u3b72 = 0.004, small), %HRmax (\u3b72 = 0.007, small), %HRmean (\u3b72 = 0.018, small), RER (\u3b72 = 0.007, small), RPE (\u3b72 = 0.007, small), and RSAbest (\u3b72 = 0.050, small). RSAmean performance significantly improved in CHO + CAF trials compared to PLA, with sprint times significantly improved from Pre to FT also (\u3b72 = 0.135, medium). A significant difference was observed in BLa between time points (Pre, HT, and FT) (\u3b72 = 0.884, large) in % HRmax (\u3b72 = 0.202, medium), %HRmean (\u3b72 = 0.477, large), and RER (\u3b72 = 0.554, large) across halves and in RPE across time points (\u3b72 = 0.670, large). Our data provide novel data regarding the effects of CHO and CAF supplementation on team sport performance, with co-ingestion of CHO + CAF reducing the decrement in repeated sprint performance compared to PLA