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Exploration under glacial sediment cover is a necessary part of modern mineral exploration in Canada. Traditional indicator methods use visual examination to identify mineral grains in the 250 to 2000 µm fraction of till heavy-mineral concentrates (HMC). This study tests automated mineralogical methods using scanning electron microscopy to identify indicator minerals in the fine (

Introduction Ameliorer le controle de l’asthme est un objectif essentiel de la prise en charge de l’asthme. L’effet du mepolizumab sur le controle de l’asthme evalue par l’Asthma Control Questionnaire-5(ACQ-5) a ete rapporte dans les essais cliniques, mais les donnees en vraie vie sont limitees. Methodes REALITI-A, etude prospective en vraie vie, multicentrique, internationale, a enrole des patients avec un asthme severe a eosinophiles (ASE), ayant initie un traitement par mepolizumab sur 51 centres dans 7 pays. Une periode de 12 mois de donnees precedant l’inclusion etait necessaire pour decrire les donnees demographiques des participants, le fardeau de l’ASE et les traitements. Le controle de l’asthme a ete evalue par l’ACQ-5. Les scores a l’initiation ont ete compares aux scores a 3,6,9 et 12 mois. Les changements du controle depuis l’initiation et le taux de participants ayant une difference minimale importante [DMI] depuis l’initiation de 0,5 unites ont ete evalues. Des modeles mixtes de mesures repetees ont ete utilises pour l’analyse. Resultats Les donnees initiales etaient disponibles pour 368 patients qui ont complete un suivi de 12 mois ( Fig. 1 ). Dix-neuf pour cent (n = 70/368) des patients ont arrete le mepolizumab dans l’annee suivant l’initiation ; les raisons les plus frequentes etaient : la decision du patient (7 % ; n = 27/368), la discretion de l’investigateur (4 % ; n = 14/368), le manque d’efficacite (4 % ; n = 13/368). A l’inclusion, les patients avaient un score moyen ACQ-5 en moindres carres (IC95 %) de 2,99 (2,85 ; 3,13). L’initiation du mepolizumab a ete associee a une amelioration du controle de l’asthme, avec des moyennes MC (IC95 %) du score ACQ-5 a 3,6,9 et 12 mois de 1,81 (1,66 ; 1,96), 1,73 (1,56 ; 1,89), 1,84 (1,62 ; 2,05), et 1,84 (1,63 ; 2,05). Dans les 3 mois, 65 % (152/234) des patients ont obtenu une DMI, passant a 71 % (84/119) apres 12 mois. Les ameliorations ont ete observees dans chaque tranche de taux d’eosinophiles sanguins a l’inclusion, avec 56 % (10/18), 60 % (9/15), et 75 % (62/83) des patients avec des taux d’eosinophiles sanguins Conclusion Cette etude prospective en vie reelle confirme l’efficacite du mepolizumab chez les patients avec un ASE en termes d’amelioration du controle de l’asthme a 3 mois, avec des ameliorations significatives du score ACQ-5. Ces resultats montrent un benefice rapide et significatif du controle de l’asthme avec le mepolizumab en vraie vie, coherent avec les resultats des essais cliniques controles.

The authors set out to evaluate the use of three sieving methods when sieving the

The dominant transient flow regime for multi-fractured horizontal wells (MFHWs) producing from low-permeability and shale (unconventional) reservoirs has historically been interpreted to be transient linear flow (TLF) with analysis performed in the framework of classical diffusion (CD). Recently, observed deviations away from this classical behavior for Permian Basin Wolfcamp shale (oil) wells have been attributed to reservoir heterogeneity and anomalous diffusion (AD). However, some wells in the basin also produce below bubble point pressure and exhibit characteristics of multi-phase flow. The objective of the current study is therefore to investigate if multi-phase flow may also be contributing to observed deviations from classic TLF behavior. The conventional log-log diagnostics used to identify flow regimes do not account for reservoir complexities such as multi-phase flow and reservoir heterogeneity. Failure to correct for these effects when they are occurring may result in misdiagnosis of flow regimes. A new workflow is therefore introduced herein to improve flow regime identification when reservoir complexities are exhibited, with a specific focus on multi-phase flow. The workflow involves the correction of log-log diagnostics for multi-phase flow through the use of modified pseudo-variables (pseudo-pressure and pseudo-time) once characteristics of multi-phase flow are identified (e.g. rapid increase of gas-oil ratio after bubble point pressure is reached). Although reservoir heterogeneity and AD are accepted causes of deviations from TLF, the impact of multi-phase flow has not been investigated in detail. Therefore, corrections to pseudo-variables for multi-phase flow, a known reservoir complexity exhibited by Wolfcamp shale wells, are presented. Pressure-dependent permeability is also accounted for in pseudo-variable calculations, although its impact is demonstrated to be relatively minor in this study. Application of the new workflow to a simulated case and a Wolfcamp shale field case demonstrates the following: 1) multi-phase flow, and in particular the appearance of a mobile gas phase after two-phase oil and water production, results in deviations from classical TLF behavior when data is analyzed using conventional (uncorrected) diagnostics; 2) application of the modified diagnostics to a simulated case that includes multi-phase flow results in the “true” flow regime signature of TLF being observed; 3) application of the modified diagnostics to a field case exhibiting evidence of multi-phase flow reduces the deviation from TLF. This study suggests that multi-phase flow may be impairing our ability to identify flow regimes using conventional flow regime identification methods.

Indicator minerals from heavy mineral concentrates have long been used in exploration for diamonds and gold, and more recently porphyry copper and volcanic massive sulphide deposits. This study is investigating the application of rapid automated mineralogy to identify and characterize indicator minerals in till and stream sediment samples. The fine (

Farmers are at increased risk of developing work-related respiratory diseases including asthma, but little is known about their occupational health and safety (OHS) knowledge and exposure prevention practices. Educational interventions may improve knowledge and practice related to prevention.To determine the feasibility of an educational intervention for farmers in a community health centre setting.This was a pilot study. Farmers were recruited by the community health centre and completed a questionnaire on symptoms, OHS knowledge and exposure prevention practices. The intervention group received education on work-related asthma and exposure control strategies, and was offered spirometry and respirator fit testing. All subjects were asked to repeat the questionnaire 6 months later.There were 68 study participants of whom 38 formed the intervention group. At baseline, almost 60% of farmers reported having received OHS training and were familiar with material safety data sheets (MSDSs); fewer (approximately 40%) reported knowledge of OHS legislation and availability of MSDSs. Approximately, two-thirds of subjects reported using respiratory protection. The response rate for repeating the questionnaire was 76% in the intervention group and 77% in the controls. Among the intervention subjects, statistically significant increases were observed in reported safety training, familiarity and availability of MSDSs and knowledge of OHS legislation.Gaps in OHS knowledge were observed. The educational intervention on OHS knowledge and exposure prevention practices in the community health centre setting was feasible. Larger, more-controlled studies should be undertaken as this study suggests a positive effect on OHS knowledge and prevention practices.

SummaryBackgroundThe Mini Asthma Quality of Life Questionnaire (MiniAQLQ) is a validated disease-specific quality of life (QOL) paper (p) questionnaire. Electronic (e) versions enable inclusion of asthma QOL in electronic medical records and research databases.PurposeTo validate an e-version of the MiniAQLQ, compare time required for completion of e- and p-versions, and determine which version participants prefer.MethodsAdults with stable asthma were randomized to complete either the e- or p-MiniAQLQ, followed by a 2-h rest period before completing the other version. Agreement between versions was measured using the intraclass correlation coefficient (ICC) and Bland–Altman analysis.ResultsTwo participants with incomplete p-MiniAQLQ responses were excluded. Forty participants (85% female; age 47.7 ± 14.9 years; asthma duration 22.6 ± 16.1 years; FEV1 87.1 ± 21.6% predicted) with both AQLQ scores 65) adults.

Marine shock mitigating seats have been shown to reduce fatigue and decrease the likelihood and severity of injury of seated persons –particularly when installed aboard high speed commercial or combatant planing craft. Not so clear is how the performance of such seating systems are characterized so informed decisions can be made as to which seats perform best in specific conditions. Standards do exist to help quantify the injury risks associated with exposure to repeated shock and whole body vibration. However, such methods are field test based and the results somewhat difficult to understand. Work by the authors is presented from their experiences in characterizing seat performance to different standards includingSed8(ISO 2631-5,1997), UK Ministry of Defense Protocol 1 (UK MoD, 2014) as well as members sitting on the new ISO TC108/SC4/WG18 subcommittee on Human Exposure to Mechanical Vibration and Shock, Testing of Shock Mitigating Marine Seats. A new method is presented that allows for results obtained by both field and laboratory seat testing to be related to injury risk and compared equally in meaningful, understandable and objective ways.

BACKGROUND--Interpretation of measurements of limited maximal airway narrowing, or plateau response, requires knowledge of its variability within subjects and between methods. METHODS--The repeatability of the plateau response to inhaled methacholine with a dosimeter (D) method (maximal dose 210 mumol) and a tidal breathing (T) method (730 mumol), and the agreement of the two methods, were measured in 16 subjects with mild or no asthma. Two tests by each method (D1,D2,T1,T2) were performed in random order over four consecutive days, with a third dosimeter (D3) test one week later. The dose producing a decrease in forced expiratory volume in one second (FEV1) of 10% (PD10) and the plateau were calculated from each dose-response curve. RESULTS--A plateau was reached in all five tests in 12 subjects and in all tests except D3 in 14 subjects. PD10 was inversely related to the plateau (r = -0.95 for D, r = -0.77 for T). The 95% ranges for differences between two determinations of the plateau in a subject were +/- 11.9% (change in FEV1), +/- 19.2%, and +/- 20.3%, estimated from D1-2 and 1-3, and T1-2 tests, respectively. From the same tests the 95% ranges for the difference of a single determination from an individual's true mean value were +/- 8.3%, +/- 13.6%, and +/- 14.3%. The limits of agreement between methods indicated that 95% of the measurements of the plateau by tidal breathing ranged from 15.2% below to 13.3% above those obtained by dosimeter. There was no significant bias between methods. Tachyphylaxis over 24 hours occurred with PD10 but not with the plateau response. CONCLUSIONS--The plateau response is a subject characteristic which is independent of the method of inhalation challenge testing. Repeatability of the plateau is low in this group of subjects with low airway responsiveness.

OBJECTIVE To test stability of insulin lispro in two insulin infusion systems over 48 h. RESEARCH DESIGN AND METHODS We used reverse-phase and size-exclusion high-performance liquid chromatography (HPLC) to determine the purity, potency, and degree of polymerization of U100 insulin lispro (Humalog) after 24- and 48-h pump cycles conducted at 37°C in five Disetronic H-TRON V100 and five MiniMed 504 pumps. Pumps were set to deliver a basal rate of 0.5 U/h and 6-U boluses at t = 0, 4, 8, 24, 24.5, 28.5, 32.5, and 48 h during each cycle. The effluent was collected into 1-ml vials, pooled at 24 or 48 h, and stored at 4°C until assay. After each 48-h run period of insulin delivery, assays for potency, polymer, and purity were performed on the pooled samples from each individual cycle. m-cresol content and the pooled reservoir content were assayed in the 48-h pooled samples. RESULTS Insulin lispro retained full HPLC potency (Δ ≤ 4%) at 48 h, with no degradation of insulin lispro to des-amidoinsulin forms (24 or 48 h). No increase in pumped insulin polymer concentration was observed following 24 h of pump flow. Nonsignificant increases of ≤0.09% (Disetronic) and ≤0.15% (MiniMed) from initial concentrations of 0.18% (polymer divided by total insulin) were detected in three of five pump cycles at 48 h when compared with 37°C paired controls. Nonsignificant decreases ( CONCLUSIONS We conclude that insulin lispro is suitable for prolonged infusion in these two medical devices when syringes and catheters are replaced at 48-h intervals.

Airway hyperresponsiveness is easily assessed by measuring the concentration or dose of an inhaled agonist that produces a defined response, e.g., PC20 or PD20. However, this measure does not assess excessive bronchoconstriction. We report the results of analyzing bronchial dose-response curves by measuring percent fall in vital capacity (delta FVC%) as the response rather than the PC20. In our analysis, delta FVC% was measured at the PC20, and therefore it was the dependent variable, whereas the concentration of agonist was the independent variable, in contrast to the usual bronchoprovocation tests in which the response is the independent variable and the dose is the dependent variable. We reasoned that a dose-dependent increase in gas trapping with histamine would detect excessive bronchoconstriction as a decrease in FVC; in contrast, PC20 measures only the ease of bronchoconstriction. In 10 patients with mild asthma the reproducibility of delta FVC% when FEV1 fell by 20%, i.e., at the PC20 concentration of histamine, taken from a greater than 6-s FVC on an otherwise standard histamine challenge test was comparable to that of PC20. In 10 healthy asymptomatic subjects there were only trivial falls (0.3%) in FVC to as much as 16 mg/ml histamine. In a retrospective study of 146 patients with mild asthma, the delta FVC% was normally distributed (13.2 +/- 5.5 SD%) and did not correlate with the number of beta 2-agonist prescriptions or the PC20, but it did correlate with the number of prescriptions written per month for oral prednisone (r = 0.55, p < 0.02). We conclude that delta FVC% when FEV1 falls by 20% is a safe method of detecting excessive bronchoconstriction, and it reveals that different asthmatics react in fundamentally different ways to the same agonist. This may be useful in detecting the asthmatic at risk for serious disease.

The purpose of this study was to examine potential contributing factors to breathlessness during bronchoconstriction, in particular, to evaluate the role of lung hyperinflation. We also wished to elucidate qualitative aspects of the unpleasant sensory experience and to identify factors that contribute to intersubject variability in subjective and objective assessments of airflow obstruction. We studied sensory-mechanical interrelationships during and after induced bronchoconstriction in 21 subjects with mild stable asthma. Breathlessness (Borg scale), spirometry, and inspiratory capacity (IC) were measured after each dose during methacholine bronchoprovocation to a maximal change (delta) in FEV1 of 50%. Breathing pattern, specific airway resistance (SRaw), plethysmographic thoracic gas volume, and maximal inspiratory mouth pressure (MIP) were recorded at baseline, at maximal response, and at full symptom recovery. End-expiratory lung volume (EELV) was derived from IC. Borg increased from 0.4 +/- 0.1 (very, very slight) at baseline to 5.0 +/- 0.5 (severe) at maximal bronchoconstriction (mean +/- SEM, p < 0.001). FEV1 fell significantly (p < 0.001) to 48% predicted at maximal response. Of the 21 subjects, 19 reported increased inspiratory rather than expiratory difficulty and predominantly described sensations of reduced inspiratory capacity and unrewarded inspiratory effort. Stepwise multiple regression analysis using delta Borg (outcome variable) versus changes in spirometry, SRaw, IC, and breathing pattern components, selected delta IC as the principal contributing factor: delta Borg = 0.09 (delta IC, %fall); n = 193, r = 0.86, p < 0.001. delta IC continued to contribute significantly (p < 0.001) to the variance in Borg ratings after accounting for delta FEV1, and it was the strongest predictor of symptom recovery (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

There is a worldwide effort to produce a soft x-ray source for submicron microlithography to manufacture future generation large scale integrated microchips. The gas puff plasma discharge has been suggested as a viable alternative for low volume facilities which require relatively low throughputs with a single aligner station. The repetition rate for such systems is limited by the large gas flow into the vacuum system with the standard electromechanical puff valve. A unique puff arrangement is being developed which will limit the dead gas flow and, in principle, will allow for the development of high repetition rate systems. In this arrangement, the gas flows continuously from a low-pressure plenum through an annular aperture into the Z-pinch electrode gap. A discharge through a single turn solenoid coil mounted on the outside of the plenum inductively heats the gas, temporarily increasing the mass flow to produce a low mass (

Insulin aggregation remains a fundamental obstacle to the long-term application of many insulin infusion systems. We here report the effects of physiologic and nonphysiologic compounds on the aggregation behavior of crystalline zinc insulin (CZI) solutions. Under conditions chosen to simulate the most severe that would be encountered in delivery systems (presence of air, continuous motion, and elevated temperature), both highly purified and regular CZI at 5 U/ml formed turbid gels in 5 days. At concentrations of 100 and 500 U/ml stability was increased with turbid gels forming at 12 and 15 days, respectively. Under identical conditions, 5 U/ml CZI formulations containing the physiologic surfactant lysophosphatidylcholine (0.02%) or the synthetic surfactants SDS (1%), Brij 35 (0.1%), Tween (0.01%), or Triton X (0.01%) retained a transmittance at 540 nm of >96% for 67–150 days. These nonionic and ionic surfactants containing the hydrophobic group, CH3(CH2)N, with N = 7–16, remarkably stabilized CZI formulations while those lacking such groups demonstrated little or no effect. The alcohols glycerol (30–50%) and isopropanol (10–50%) were moderately effective stabilizers. Silicone rubber drastically accelerated aggregation in all but one formulation (1% SDS). Emphasis in this study was placed on the properties of 5-U/ml formulations. Controls run at higher concentrations indicated a positive correlation between concentration and stability. It was concluded that the aggregation of insulin into high-molecular-weight polymers may be inhibited by reducing the effective polarity of the solvent. In this regard, anionic and nonionic surfactants containing appropriately long hydrophobic groups demonstrated the greatest degree of stabilization. Finally, of all the medical grade materials likely to be used in pumps, silicone rubber is the most active in promoting insulin aggregation.

By inducing an electrical discharge in an annular gas plenum connected to a vacuum diode by a narrow annular slit, we demonstrate that microgram preionized plasma liners can be formed and imploded by a dc charged Blumlein pulser to efficiently convert electrical energy into soft x rays. The submillimeter x‐ray source can in principle be scaled to the high repetition rate needed for x‐ray lithography. In a proof of principle experiment, we have observed using krypton up to 0.5, 20, and 100 J of x‐ray output above 1.5 keV, 500 eV, and 150 eV photon energies, respectively.

Insulin is insoluble in water at physiological pH, but dissolves relatively rapidly in plasma. To quantify the ability of various solutions to dissolve crystalline insulin, a simple assay measuring dissolution time was developed. At pH 7.5 and room temperature, distilled water, 0.154 mol/l NaCl, Ringer's lactate solution, and 5% albumin in 0.154 mol/l NaCl did not dissolve insulin crystals within 30 min. Normal postprandial human plasma and a protein-free cell culture medium dissolved insulin crystals within 3 to 8 min. This ability was inhibited by acid titration of the fluids to a stable pH of 6.30, at which point bicarbonate depletion could be implied. Repletion of bicarbonate did restore the ability of these solutions to dissolve insulin crystals, but back-titration to the initial pH with NaOH did not. The effect of sodium bicarbonate alone was strongly concentration dependent above 23 mmol/l. We suggest that the ability of physiological fluids to dissolve insulin crystals at normal pH depends on their bicarbonate content. The ability to dissolve insulin with a physiological solvent which prevents its reaggregation promises to facilitate its use in portable pumping systems.

A simple theory for Trichel discharges in gases is proposed, in which the corona region is assumed to be describable in terms of a Townsend generation-recombination mechanism, while the outer drift region is deemed subject to photoionisation-attachment processes, together with displacement current effects. The pair of first-order nonlinear differential equations is examined with a linearising 'small signal' procedure, yielding stability limits, frequency and damping coefficients. A numerical treatment of the full equations gives the development of pulse shapes, as well as large-signal modifications of the stability limits. Good qualitative agreement with observation is established, especially with the well-known proportionality between average current and pulse frequency. An extension of the theory to stepped-leader phenomena is proposed and it is shown that the agreement with observation is quite acceptable, even though the parameters involved here are of a different order of magnitude when compared with Trichel discharges.

Exogenous insulin exists primarily as the monomer in human plasma. However, in U100 regular insulin formulations, the concentrations of zinc and peptide are such that the insulin hexamer predominates. The biologic result is further disassociation to the monomer after subcutaneous or i.v. administration. Because of this, human plasma from seven normal controls dissolved 20-30 microm hexagonal insulin crystals in 3-8 min. This ability was inhibited by acid titration to a stable pH of 6.30, at which point bicarbonate depletion could be suggested. Repletion of bicarbonate remarkably restored the solvent effect, while back-titration to the initial pH without repleting bicarbonate had only a moderate result. To establish whether the in vivo reduction of bicarbonate in pathologic states had similar results, plasma from five Type I diabetics in severe acidosis (pH 7.06 +/- 0.04, HCO3 -7.3 +/- 0.6 mmol/l) was similarly studied after stabilization under 5% CO2 (pH, 6.97-7.17). In all cases, the dissolution of insulin crystals was inhibited (dissolution times greater than 25 min). When bicarbonate was replenished (HCO3- 24.1-26.7 mmol/l) and pH accordingly renormalized (pH 7.39-7.43), the dissolution of insulin crystals was completely restored. Because of these observations, we conclude that both plasma bicarbonate and pH markedly affect the dissolution of insulin and that reduced bicarbonate/pH in diabetic ketoacidosis may limit the availability of the biologically active monomer. These influences may play a role in the initial insensitivity to insulin frequently seen in severe insulin deficiency and ketoacidosis.

Abrupt changes in flow path, motion, elevated temperatures, metal ion contamination, impure insulin formulations, CO2 diffusion, pH drop, dissimilar metal pump components, salt concentration, inappropriate diluents, elevated temperatures, refrigeration temperatures, processing, insulin heterogeneity, and buffering systems have been implicated to a greater or lesser extent in the plugging of insulin delivery devices. Before the rate at which insulin loses its biological activity in delivery systems can be assessed it is obvious that anti-aggregating diluents must be developed and subjected to long-term testing both in vitro and in vivo. Until such stable homogenous formulations are available the knowledge presented in this article will serve to decrease, but not eliminate, the problem of insulin aggregation in delivery systems. Further experiments are in progress and preliminary results [41] provide evidence that the problems cited are not without resolution. In this regard serum apparently contains factor(s) that promote the dissolution of insulin and prevent the formation of peptide aggregates in dilute solutions [41]. Many laboratories are now working to resolve the problem of insulin aggregation in artificial delivery devices.

Optimum designing of an imploding liner system consists of matching the liner dimensions and mass to the driver parameters to achieve high‐energy density in the final pinch phase. Contours of energy efficiency and dimensionless power at the time of liner collapse have been plotted in the space defined by the Katzenstein dimensionless parameters A and B. These plots are shown to be very useful for studying and designing imploding liner systems.