Three-dimensional trajectory analyses of two drop sizing instruments: PMS OAP and PMS FSSP

Flow induced distortions of water drop fluxes and speeds seen by the instruments were predicted by use of three dimensional flow and trajectory calculation methods. Sensitivities were determined for the instruments, in isolation and mounted under the wing of an airplane, to: water drop diameter (2 to 1000 microns), angle of attack and free stream air speed. For the optical array probe in isolation and on the airplane at 0 deg angle of attack, flux distortions of practical consequence are not found. At 4 deg airplane angle of attack, partial flow stagnation under the uptilted wing causes significant decreases in both flux and speed for cloud size droplets. For the forward scattering spectrometer probe in isolation, only marginally significant sensitivities to free stream air speed are found, and no sensitivity is found to angle of attack. Both speed and flux of cloud size droplets are predicted to be undermeasured by from 12 to 24 percent depending on airplane angle of attack. For the wing-mounted instruments, effects of flow about the instruments themselves are found to be equal in importance to effects of flow about the airplane. Preferred orientation (canting) angles of distorted water drops are found to be functions of drop size, angle of attack and air speed

Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD

Dirkje S Postma,1 Nicolas Roche,2 Gene Colice,3 Elliot Israel,4 Richard J Martin,5 Willem MC van Aalderen,6 Jonathan Grigg,7 Anne Burden,8 Elizabeth V Hillyer,8 Julie von Ziegenweidt,8 Gokul Gopalan,9 David Price8,10 1University of Groningen, Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 2Respiratory and Intensive Care Medicine, Cochin Hospital Group, APHP, Paris-Descartes University (EA2511), Paris, France; 3Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center and George Washington University School of Medicine, Washington DC, USA; 4Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, National Jewish Health, Denver, CO, USA; 6Dept of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital AMC, Amsterdam, the Netherlands; 7Blizard Institute, Queen Mary University London, London, UK; 8Research in Real Life, Ltd, Cambridge, UK; 9Respiratory, Global Scientific Affairs, Teva Pharmaceuticals, Frazer, PA, USA; 10Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2–4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD. Patients and methods: Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year. During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection. Results: Mean patient age was 67 years, 57%–60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period. Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32–4.73). Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 µg/day versus 436 µg/day for initiation, 438 µg/day versus 534 µg/day for step-up patients). Conclusion: We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years' follow-up. Keywords: COPD exacerbation, extrafine particle, matched cohort analysis, real life, small airway

Contraction of the Ventral Abdomen Potentiates Extracardiac Retrograde Hemolymph Propulsion in the Mosquito Hemocoel

BACKGROUND: Hemolymph circulation in mosquitoes is primarily controlled by the contractile action of a dorsal vessel that runs underneath the dorsal midline and is subdivided into a thoracic aorta and an abdominal heart. Wave-like peristaltic contractions of the heart alternate in propelling hemolymph in anterograde and retrograde directions, where it empties into the hemocoel at the terminal ends of the insect. During our analyses of hemolymph propulsion in Anopheles gambiae, we observed periodic ventral abdominal contractions and hypothesized that they promote extracardiac hemolymph circulation in the abdominal hemocoel. METHODOLOGY/PRINCIPAL FINDINGS: We devised methods to simultaneously analyze both heart and abdominal contractions, as well as to measure hemolymph flow in the abdominal hemocoel. Qualitative and quantitative analyses revealed that ventral abdominal contractions occur as series of bursts that propagate in the retrograde direction. Periods of ventral abdominal contraction begin only during periods of anterograde heart contraction and end immediately following a heartbeat directional reversal, suggesting that ventral abdominal contractions function to propel extracardiac hemolymph in the retrograde direction. To test this functional role, fluorescent microspheres were intrathoracically injected and their trajectory tracked throughout the hemocoel. Quantitative measurements of microsphere movement in extracardiac regions of the abdominal cavity showed that during periods of abdominal contractions hemolymph flows in dorsal and retrograde directions at a higher velocity and with greater acceleration than during periods of abdominal rest. Histochemical staining of the abdominal musculature then revealed that ventral abdominal contractions result from the contraction of intrasegmental lateral muscle fibers, intersegmental ventral muscle bands, and the ventral transverse muscles that form the ventral diaphragm. CONCLUSIONS/SIGNIFICANCE: These data show that abdominal contractions potentiate extracardiac retrograde hemolymph propulsion in the abdominal hemocoel during periods of anterograde heart flow

Prospective multi-center study of oncologic outcomes of robot-assisted partial nephrectomy for pT1 renal cell carcinoma

BACKGROUND: Partial nephrectomy has been increasingly recommended over radical nephrectomy for the management of small renal masses based on improved renal functional outcomes without sacrifice of oncologic effectiveness. Robot-assisted partial nephrectomy (RAPN) has been introduced in an effort to offer another minimally invasive option for nephron-sparing surgery. However, reports of RAPN have been limited to short-term perioperative outcomes. The goal of this study is to report and evaluate the initial oncologic outcomes of RAPN. Utilizing prospectively obtained data on RAPN performed by four surgeons at four separate tertiary care centers, we selected patients with unilateral, localized, non-familial, pathologically-confirmed pT1 renal cell carcinoma and a minimum post-operative follow-up of 12 months. METHODS: Utilizing prospectively obtained data on RAPN performed by four surgeons at four separate tertiary care centers, we selected patients with unilateral, localized, non-familial, pathologically-confirmed pT1 renal cell carcinoma and a minimum post-operative follow-up of 12 months. Survival analysis (disease-free, cancer-specific, and overall survival) was performed, and Kaplan-Meier curves were generated. RESULTS: RAPN was performed in 124 patients with a median tumor size of 3.0 cm (IQR 2.2-4.2 cm). Median follow-up was 29 months (range 12-46 months). Positive parenchymal surgical margins occurred in two patients (1.6 %), both of whom were recurrence-free at 30 and 34 months after surgery. The three-year Kaplan-Meier estimated disease-free survival was 94.9 %, cancer-specific survival was 99.1 %, and overall survival was 97.3 %. CONCLUSIONS: In our cohort of patients with small renal carcinomas who were followed for a median of 29 months, recurrence and survival outcomes were similar to those reported for open and laparoscopic partial nephrectomy. Further long-term outcomes will be needed to definitively claim that RAPN is oncologically equivalent to other surgical approaches

Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

Asthma management guidelines recommend adding a long-acting β2-agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.Research in Real-Life ltd. Teva Pharmaceutical Industries

Leukotriene antagonists as first-line or add-on asthma controller therapy

Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score =6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score =1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group

Complex effects of temperature on mosquito immune function

Over the last 20 years, ecological immunology has provided much insight into how environmental factors shape host immunity and host–parasite interactions. Currently, the application of this thinking to the study of mosquito immunology has been limited. Mechanistic investigations are nearly always conducted under one set of conditions, yet vectors and parasites associate in a variable world. We highlight how environmental temperature shapes cellular and humoral immune responses (melanization, phagocytosis and transcription of immune genes) in the malaria vector, Anopheles stephensi. Nitric oxide synthase expression peaked at 30°C, cecropin expression showed no main effect of temperature and humoral melanization, and phagocytosis and defensin expression peaked around 18°C. Further, immune responses did not simply scale with temperature, but showed complex interactions between temperature, time and nature of immune challenge. Thus, immune patterns observed under one set of conditions provide little basis for predicting patterns under even marginally different conditions. These quantitative and qualitative effects of temperature have largely been overlooked in vector biology but have significant implications for extrapolating natural/transgenic resistance mechanisms from laboratory to field and for the efficacy of various vector control tools

Assessing Cognitive Abilities in High-Performing Cochlear Implant Users

Despite being considered one of the most successful neural prostheses, cochlear implants (CIs) provide recipients with a wide range of speech perception performance. While some CI users can understand speech in the absence of visual cues, other recipients exhibit more limited speech perception. Cognitive skills have been documented as a contributor to complex auditory processing, such as language understanding; however, there are no normative data for existing standardized clinical tests assessing cognitive abilities in CI users. Here, we assess the impact of modality of presentation (i.e., auditory-visual versus visual) for the administration of working memory tests in high-performing CI users in addition to measuring processing speed, cognitive efficiency and intelligence quotient (IQ). Second, we relate performance on these cognitive measures to clinical CI speech perception outcomes.Methods: Twenty one post-lingually deafened, high-performing, adult CI users [age range: 52–88 years; 3 unilateral CI, 13 bimodal (i.e., CI with contralateral hearing aid), 5 bilateral CI] with clinical speech perception scores (i.e., AzBio sentences in quiet for the first-ear CI) of ≥60% were recruited. A cognitive test battery assessing auditory-visual working memory (AVWM), visual working memory (VWM), processing speed, cognitive efficiency and IQ was administered, in addition to clinical measures of speech perception in quiet (i.e., AzBio sentences in quiet). AzBio sentences were assessed in two conditions: first-ear CI only, and best-aided everyday wearing condition. Subjects also provided self-reported measures of performance and benefit from their CI using standardized materials, including the Glasgow Benefit Inventory (GBI) and the Nijmegen Cochlear Implant questionnaire (NCIQ).Results: High-performing CI users demonstrated greater VWM than AVWM recall. VWM was positively related to AzBio scores when measured in the first-ear CI only. AVWM, processing speed, cognitive efficiency, and IQ did not relate to either measure of speech perception (i.e., first-ear CI or best-aided conditions). Subjects’ self-reported benefit as measured by the GBI predicted best-aided CI speech perception performance.Conclusion: In high-performing CI recipients, visual presentation of working memory tests may improve our assessment of cognitive function