Advanced Configurations for Very Large Subsonic Transport Airplanes

Recent aerospace industry interest in developing a subsonic commercial transport airplane with 50 percent greater passenger capacity than the largest existing aircraft in this category (the Boeing 747-400 with approximately 400-450 seats) has generated a range of proposals based largely on the configuration paradigm established nearly 50 years ago with the Boeing B-47 bomber. While this basic configuration paradigm has come to dominate subsonic commercial airplane development since the advent of the Boeing 707/Douglas DC-8 in the mid-1950's, its extrapolation to the size required to carry more than 600-700 passengers raises several questions. To explore these and a number of related issues, a team of Boeing, university, and NASA engineers was formed under the auspices of the NASA Advanced Concepts Program. The results of a Research Analysis focused on a large, unconventional transport airplane configuration for which Boeing has applied for a patent are the subject of this report. It should be noted here that this study has been conducted independently of the Boeing New Large Airplane (NLA) program, and with the exception of some generic analysis tools which may be common to this effort and the NLA (as will be described later), no explicit Boeing NLA data other than that published in the open literature has been used in the conduct of the study reported here

A survey of phytoestrogenic activity in Kansas flint hills pastures

The botanical composition and basal cover of three Kansas Flint Hills pastures located in Butler and Chase counties was surveyed to estimate the incidence of plant species that contain appreciable levels of estrogenic activity. Many-flowered scurfpea and Ladino clover were the only plant species classified as high in estrogenic activity. Although significant estrogenic activity existed in specific species, the willingness of livestock to consume those species is unclear

Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money

Fundamental and applied studies of helium ingrowth and aging in plutonium

This is the final report of a two-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The purpose of this project was to develop new capabilities to assess the nucleation and growth of helium-associated defects in aged plutonium metal. This effort involved both fundamental and applied models to assist in predicting the transport and kinetics of helium in the metal lattice as well as ab initio calculations of the disposition of gallium in the fcc plutonium lattice and its resulting effects on phase stability. Experimentally this project aimed to establish experimental capabilities crucial to the prediction of helium effects in metals, such as transmission electron microscopy, thermal helium effusion, and the development of a laser-driven mini-flyer for understanding the role of helium and associated defects on shock response of plutonium surrogates

Evaluation of Ralgro® on pasture and subsequent feedlot performance and carcass merit of mexican crossbred steers

A pasture/feedlot field study was conducted to evaluate the effects of a single Ralgro® implant during the stocker phase on steer grazing performance and subsequent feedlot performance and carcass merit. A total of 2,764 steers of Mexican origin averaging 449 lb were assembled in Texas and shipped to Kansas, where they grazed on three intensively-early-stocked Flint Hills pastures. At initial processing, the steers were individually weighed and randomly assigned to either a non-implanted control group or a Ralgro implant group. Ralgro steers gained more (23 lb; P<0.01) than controls during the 82- to 93-day grazing phase. Following the grazing phase, all steers were shipped to a commercial feedlot in southwestern Kansas where steers from each pasture were individually weighed and given a single Component E-S® implant. Immediately after processing, steers from each pasture were sorted into either a light- or heavy-weight pen, regardless of pasture implant treatment, resulting in six feedlot pens. Days on feed ranged from 127 to 197. Control steers gained faster (P<0.01) during the feedlot phase; however, Ralgro steers had higher cumulative weight gains across the combined pasture and feedlot phases (P<0.01) and averaged three fewer days on feed (P<0.05). There were no significant differences for marbling, fat thickness, ribeye area, KPH fat, or yield grade. Ralgro steers had lower (P<0.05) quality grades because of a higher incidence (P<0.001) of steers with B and C carcass maturities

Distance learning improves attainment of professional milestones in the early years of surgical training

OBJECTIVES: To assess the impact of a surgical sciences e-learning programme in supporting the academic development of surgical trainees during their preparation for professional examination. BACKGROUND: In 2007, a 3-year online part-time Master of Surgical Sciences (MSc) degree programme was launched, utilizing an innovative platform with virtual case scenarios based on common surgical conditions addressed by the curriculum relating to the Membership Examination of the Royal Colleges of Surgeons (MRCS). Multiple-choice questions with feedback and discussion boards facilitated by expert clinical tutors provided formative assessment. Summative assessment comprised written examination at the end of each of the first 2 years (equivalent to MRCS level), culminating in submission of a research dissertation in year 3 toward an MSc. METHODS: Students' age, gender, and level at entry to the programme were documented. Anonymized student feedback from 2008 to 2012 was examined using online questionnaires, and performance in the MSc programme was compared to MRCS examination outcomes for students who had consented to release of their results. RESULTS: A total of 517 surgical trainees from 40 countries were recruited over the 6-year period, and 116 MSc students have graduated to date. Of 368 students, 279 (76%) were foundation doctors (interns) and had not commenced formal surgical training on enrolling in the MSc programme. However, level at entry did not influence performance (P > 0.05 across all 3 years). Average pass rates since the programme launched, for those students completing all of the required assessments, were 84% ± 11% in year 1, 85% ± 10% in year 2, and 88% ± 7% in year 3 of the MSc programme. MSc students had significantly higher MRCS pass rates than nonenrolled trainees (67% vs 51%, P < 0.01, n = 352). There was a significant correlation between MRCS examination performance and overall performance in the MSc (R(2) = 58%; P < 0.01, n = 37). Of 248 respondents, 202 (81%) considered that the MSc would improve their chances of gaining a surgical training post, and 224 (90%) would recommend the programme to their peers. CONCLUSIONS: The online MSc programme supports academic development of trainees in the early years of surgical training, is well received by students, and is associated with improved success in their professional examination

A reappraisal of explosive–effusive silicic eruption dynamics: syn-eruptive assembly of lava from the products of cryptic fragmentation

Silicic volcanic eruptions range in style from gently effusive to highly explosive, and may switch style unpredictably during a single eruption. Direct observations of subaerial rhyolitic eruptions (Chaiten 2008, Cordón Caulle 2011–2012, Chile) challenged long-standing paradigms of explosive and effusive eruptive styles and led to the formulation of new models of hybrid activity. However, the processes that govern such hybrid explosive–effusive activity remain poorly understood. Here, we bring together observations of the well-studied 2011–2012 Cordón Caulle eruption with new textural and petrologic data on erupted products, and video and still imagery of the eruption. We infer that all of the activity – explosive, effusive, and hybrid – was fed by explosive fragmentation at depth, and that effusive behaviour arose from sticking and sintering, in the shallow vent region, of the clastic products of deeper, cryptic fragmentation. We use a scaling approach to determine that there is sufficient time available, during emplacement, for diffusive pyroclast degassing and sintering to produce a degassed plug that occludes the shallow conduit, feeding clastogenic, apparently effusive, lava-like deposits. Based on evidence from Cordón Caulle, and from other similar eruptions, we further argue that hybrid explosive–effusive activity is driven by episodic gas-fracking of the occluding lava plug, fed by the underlying pressurized ash- and pyroclast-laden region. The presence of a pressurized pocket of ash-laden gas within the conduit provides a mechanism for generation of harmonic tremor, and for syn-eruptive laccolith intrusion, both of which were features of the Cordón Caulle eruption. We conclude that the cryptic fragmentation models is more consistent with available evidence than the prevailing model for effusion of silicic lava that assume coherent non-fragmental rise of magma from depth to the surface without wholesale explosive fragmentation

Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease

Inflammation is an important factor in Alzheimer’s disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman’s correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer’s Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman’s correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3–9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.</p

HacA-Independent Functions of the ER Stress Sensor IreA Synergize with the Canonical UPR to Influence Virulence Traits in Aspergillus fumigatus

Endoplasmic reticulum (ER) stress is a condition in which the protein folding capacity of the ER becomes overwhelmed by an increased demand for secretion or by exposure to compounds that disrupt ER homeostasis. In yeast and other fungi, the accumulation of unfolded proteins is detected by the ER-transmembrane sensor IreA/Ire1, which responds by cleaving an intron from the downstream cytoplasmic mRNA HacA/Hac1, allowing for the translation of a transcription factor that coordinates a series of adaptive responses that are collectively known as the unfolded protein response (UPR). Here, we examined the contribution of IreA to growth and virulence in the human fungal pathogen Aspergillus fumigatus. Gene expression profiling revealed that A. fumigatus IreA signals predominantly through the canonical IreA-HacA pathway under conditions of severe ER stress. However, in the absence of ER stress IreA controls dual signaling circuits that are both HacA-dependent and HacA-independent. We found that a ΔireA mutant was avirulent in a mouse model of invasive aspergillosis, which contrasts the partial virulence of a ΔhacA mutant, suggesting that IreA contributes to pathogenesis independently of HacA. In support of this conclusion, we found that the ΔireA mutant had more severe defects in the expression of multiple virulence-related traits relative to ΔhacA, including reduced thermotolerance, decreased nutritional versatility, impaired growth under hypoxia, altered cell wall and membrane composition, and increased susceptibility to azole antifungals. In addition, full or partial virulence could be restored to the ΔireA mutant by complementation with either the induced form of the hacA mRNA, hacAi, or an ireA deletion mutant that was incapable of processing the hacA mRNA, ireAΔ10. Together, these findings demonstrate that IreA has both HacA-dependent and HacA-independent functions that contribute to the expression of traits that are essential for virulence in A. fumigatus