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Trung N Tran,1 Heath Heatley,2 Arnaud Bourdin,3 Andrew Menzies-Gow,4,5 David J Jackson,6 Ekaterina Maslova,5 Jatin Chapaneri,5 William Henley,2,7 Victoria Carter,2 Jeffrey Shi Kai Chan,2 Cono Ariti,2 John Haughney,8,9 David Price2,9 1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Department of Respiratory Diseases, PhyMedExp, University of Montpellier, Montpellier, France; 4Royal Brompton & Harefield Hospitals and School of Immunology & Microbial Sciences, King’s College London, London, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Guy’s Severe Asthma Centre, Guy’s and St Thomas’ Hospitals, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7Department of Health and Community Sciences University of Exeter Medical School, Exeter, UK; 8NHS Clinical Research Facilities, Glasgow, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription.Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥ 4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥ 90-day gap] and frequent [< 90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns.Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£ 3902 vs £ 2722 and £ 8623 vs £ 4929, respectively), as were mean annualized costs (£ 565 vs £ 313 and £ 1526 vs £ 634, respectively). A dose–response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001).Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care.Keywords: asthma, costs, healthcare resource utilization, intermittent, oral corticosteroids

Richard Hubbard, Victoria Carter, William Henley, David Price Observational and Pragmatic Research Institute, Cambridge, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 5 Coles Lane, Cambridge, CB24 3BA, UK, Email dprice@opri.sg

David Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif &Scedil;en,9 Dave Singh,10 Claus F Vogelmeier,11 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 Joan B Soriano,13 Maxim Kots,12 George Georges14 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Department of Health and Community Sciences, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Hospital and Institute (UMR1016), Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A, Parma, Italy; 13Respiratory Department, Hospital Universitario de La Princesa and Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; 14Global Clinical Development, Chiesi Farmaceutici, S.p.A, Parma, ItalyCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Combined ICS and long-acting bronchodilators (LABD) more effectively reduce COPD exacerbations than LABD therapy alone. Corticosteroid-related adverse effects, including pneumonia, limit ICS use. Previous data suggest this risk is lower for extrafine beclometasone (ef-BDP). We compared pneumonia risk among new users of fixed dose ICS/LABD formulations containing ef-BDP, versus patients initiating LABD without any ICS.Methods: A propensity-matched historical cohort study design used data from OPCRD. COPD patients with ≥ 1 year of continuous data who initiated LABD or ICS/LABD formulations containing ef-BDP were matched. Primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions, with non-inferiority boundary of 15%.Results: 23,898 COPD patients were matched, who were 68± 11 years, 54.3% male and 56% current-smokers, while 43% were former-smokers. Initiation of ef-BDP/LABD was not associated with an increased risk of pneumonia versus LABD, for either a sensitive 0.89 (0.78– 1.02), P = 0.08 or a specific 0.91 (0.78– 1.05), P = 0.18 definition of pneumonia. The probability of remaining pneumonia free 1-year after ef-BDP/LABD was 98.4%, which was comparable to LABD at 97.7%, and was sustained up to 6 years of observation; non-inferiority criterion was met for both definitions. Initiation of ef-BDP/LABD was also associated with a reduced risk of developing LRTIs in the propensity matched cohort.Conclusion: Risk of pneumonia when using ICS for the management of COPD reported in several randomised controlled trials may not be relevant with ef-BDP in a diverse real-world clinical population.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclometasone, long-acting bronchodilators

David B Price,1,2 William Henley,1,3 José Eduardo Delfini Cançado,4 Leonardo M Fabbri,5 Huib AM Kerstjens,6 Alberto Papi,7 Nicolas Roche,8 Elif &Scedil;en,9 Dave Singh,10 Claus F Vogelmeier,11 Sara Barille,12 Elena Nudo,12 Victoria Carter,1 Derek Skinner,1 Rebecca Vella,1 George Georges13 1Observational and Pragmatic Research Institute, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Health Statistics Group, Institute of Health Research, University of Exeter Medical School, Exeter, UK; 4Santa Casa de São Paulo Medical School, São Paulo, Brazil; 5Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 6Department of Pulmonary Diseases, University of Groningen and University Medical Centre Groningen, and Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands; 7Respiratory Medicine, University of Ferrara, Ferrara, Italy; 8Department of Respiratory Medicine, APHP-Centre University of Paris, Cochin Institute, Paris, France; 9Department of Pulmonary Medicine, Ankara University School of Medicine, Ankara, Turkey; 10Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Global Medical Affairs, Chiesi Farmaceutici, S.p.A., Parma, Italy; 13Global Clinical Development, Chiesi Farmaceutici, S.p.A., Parma, ItalyCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, 573969, Singapore, Email dprice@opri.sgBackground: Inhaled corticosteroids (ICS) afford therapeutic benefits in some COPD patients, but their widespread use is cautioned due to an increased risk of developing pneumonia. Subclass variations exist, and the risk profile differs for individual ICS. Formulation particle size has been identified as a potential effect modifier. The present study compared the risk of pneumonia among new COPD users of fixed-dose combination inhalers containing fine-particle fluticasone (fp-FDC-F) versus extrafine particle beclometasone (ef-FDC-BDP).Methods: A propensity matched historical cohort study was conducted using data from the Optimum Patient Care Research Database. COPD patients aged ≥ 40 years with ≥ 1 year of continuous medical data who initiated fp-FDC-F or ef-FDC-BDP were compared. The primary outcome was time to pneumonia event, as treated, using either sensitive (physician diagnosed) or specific (physician diagnosed and x-ray or hospital admission confirmed) definitions.Results: A total of 13,316 patients were matched. Initiation of fp-FDC-F (mean dosage furoate 99 μg; propionate 710 μg) was associated with an increased risk of pneumonia versus ef-FDC-BDP (mean beclometasone dose 395 μg), irrespective of definition (sensitive HR 1.38 95% CI 1.14– 1.68; specific HR 1.31 95% CI 1.05– 1.62).Conclusion: In the current investigation, we found that in comparison to extrafine beclomethasone, commencing a formulation containing fluticasone is associated with an increased risk of developing pneumonia. These observations support the idea that not all ICS are equal in their adverse effects and subclass variations exist and should be carefully considered in the treatment choice.Keywords: inhaled corticosteroids, pneumonia, COPD, extrafine beclomethasone, fluticasone

A method with the ability to increase greatly both the resolution and efficiency of a given capillary electrophoretic system is described. This method differs from traditional capillary electrophoresis (CE) in that a counterflow is induced in the direction opposite to the electrokinetic migration of the analyte. This has the effect of extending not only the time the analytes migrate in the electric field but also the effective length and the effective applied voltage of the system. Previous work in our group with flow counterbalanced capillary electrophoresis has utilized an open tube of small inner diameter to reduce peak broadening caused by hydrodynamic flow. Narrowdiameter capillaries (5-10 [micro]m) restricted analysis to fluorescent analytes and laser-induced fluorescence detection. The method described here uses a capillary of much larger inner diameter (75 [micro]m) that has been packed with nonporous silica particles. The packing material reduces the amount of band broadening caused by pressure-induced flow relative to that experienced in an open tube. A larger diameter capillary allows the detection of analytes by UV absorption, not only eliminating the need to tag analytes with fluorescent tags but also allowing for the detection of a much broader range of analytes. The system was evaluated by studying the separations of several enantlomers using only [beta]-cyclodextrin as the chiral selector. The system was also used to resolve the two naturally occurring isotopes of bromine and to resolve phenylalanine from phenylalanine-[d.sub.8]. Relative to traditional CE, large improvements in resolution and separation efficiency have been achieved with this method.

The spin-on technique being an efficient method incorporates in the Si porous structure the rare earth dopants such as erbium. An extremely intense Er-related Infrared photoluminescence (IR PL) was observed following drive-in of Er in the porus Si skeleton.

Commercial cultivation of eukaryotic microalgae has so far employed a unicellular form of species only (e.g., Chlorella pyrenoidosa, Dunaliella salina, and Haematococcus pluvialis). In this study, we assessed the feasibility of using the filamentous eukaryotic microalga Klebsormidium sp. LGX80 as a new cultivar for biomass and lipid production. The effects of different forms and concentrations of nitrogen on growth and lipid production of Klebsormidium sp. LGX80 were studied by using a glass column (ø4.5 × 60 cm) photobioreactor under laboratory conditions. Growth and lipid production of the new strain were further evaluated in an outdoor pilot‐scale tubular photobioreactor. The results showed that when supplied with urea as a source of nitrogen Klebsormidium sp. LGX80 yielded a final biomass concentration of 8.49 ± 0.10 g · L−1 in which a cellular lipid content was 59.2 ± 0.4% DW. Under such conditions, the biomass and lipid productivities were 471.7 ± 5.9 and 248.1 ± 0.0 mg · L−1 · d−1, respectively. Fatty acid analysis revealed that the main fatty acids of Klebsormidium sp. LGX80 were palmitic acid (C16:0), linoleic acid (C18:2ω6), and linolenic acid (C18:3ω3), of which linoleic acid (C18:2ω6) accounted for up to 67.5 ± 0.1% of total fatty acids. When grown outdoors in a 13,000‐L tubular photobioreactor with an initial nitrogen concentration of 3 mM urea, Klebsormidium sp. LGX80 reached the highest biomass concentration of 2.63 ± 0.09 g · L−1 with the cells containing 38.0 ± 0.5% lipids (% DW), resulting in the volumetric biomass and lipid productivities of 147.2 ± 3.6 and 37.9 ± 0.9 mg · L−1 d−1, respectively. The results of light:dark cycle experiment showed that a durative and prolonged light irradiation hindered the biosynthesis of chlorophyll a and chlorophyll b in the cells, but promoted the carotenoid accumulation. These results suggested that Klebsormidium sp. LGX80 can be a potential oleaginous filamentous microalga for commercial production of microalgal oils. [ABSTRACT FROM AUTHOR]

Although desmids typically inhabit freshwater environments characterized by low amounts of nutrients and low salinity, several desmid species have been recorded in eutrophic waters, indicating their adaptation to elevated pollution and conductivity. This study aimed to determine whether desmids could be used for remediation of moderately saline aquaculture wastewater (AWW) from a fish farm situated in the southeast of Sweden. Fourteen desmid strains isolated from different climates (tropical to polar) and trophic conditions (oligotrophic to eutrophic) were cultivated in diluted AWW and we estimated their growth rates, biomass, nutrient removal efficiency, chlorophyll fluorescence parameters and cellular C, N and P quotas. Despite being grown at moderate salinity, unfavourable N:P ratio, and relatively low light/temperature regime the eutrophic strains, Cosmarium humile, Cosmarium laeve and a meso‐oligotrophic species Cosmarium impressulum, completely absorbed nitrate and phosphate from AWW media after 7 d, indicating their potential for remediation of fish effluents in colder climates. These species, along with the typical eutrophic species, Cosmarium meneghinii and Staurastrum chaetoceras, had biomass in the range 0.45–1.19 g · L−1 while maximum growth rates ranged from 0.36 to 0.51 · d−1, similar to published rates for several fast‐growing green microalgae cultivated in various AWW types. Tropical desmids had distinctly high values of saturating irradiance (Ik > 1,000 µmol photons · m−2 · s−1), and, along with eutrophic desmids, had high potential electron transport (rETRmax > 155 rel. units). Hence, the desmids studied demonstrated inherent photophysiological responses corresponding to their climate and trophic origin under the suboptimal growth conditions. [ABSTRACT FROM AUTHOR]

Our aim was to develop a novel medium for the large‐scale production of protein‐rich Arthrospira with potential applications as a biofertilizer. The novel culture medium, termed as FM‐II, was formulated using low‐cost commercial chemicals and specifically designed to improve protein production. Both Arthrospira platensis and Arthrospira maxima were produced using FM‐II and Arnon medium, which was used as a control. Photosynthetic status of the cells, which was checked by measuring chlorophyll fluorescence, biomass dry weight and protein content, was assessed daily. Arthrospira platensis had higher biomass and protein productivities than A. maxima when cultured in both control and FM‐II media. Incorporation of varied micronutrients into FM‐II formulation did not improve biomass productivity. Maximum biomass dry weight in FM‐II and control medium was 2.9 and 2.5 g · L−1, respectively. Total protein content of the biomass ranged between 55% and 65%, suggesting potential for being used in the development of high‐value agricultural products. As some nutrients were discarded unused, the initial content of phosphates and bicarbonates was reduced by 75% and 50%, respectively, without affecting the process productivity. Results reported herein could promote the production and utilization of Arthrospira platensis by significantly reducing productions costs and therefore increasing the feasibility of the process. [ABSTRACT FROM AUTHOR]

Harmful cyanobacterial blooms (CyanoHABs) are a rapidly proliferating global problem, threatening the use and sustainability of our freshwater resources. In recent decades, the United States, China, and other developed and developing countries threatened by CyanoHAB expansion have established collaborative efforts aimed at mitigating and managing this environmental and human health problem. However, an escalating negative political climate and restrictive policies on scientific exchange threaten these efforts. In this Perspective, I point to progress that has been made to counter the CyanoHAB problem on U.S.–Chinese fronts through our collaborations, which have been mutually beneficial from research and academic perspectives. Much like global efforts now needed to control pandemics, we are all "in the same boat" when to comes to countering the threat CyanoHABs pose for drinkable, swimmable, and fishable freshwater supplies and human health. [ABSTRACT FROM AUTHOR]

To test the hypothesis that rotifers release one or more chemical microalgal growth inhibitors in addition to devouring the microalgal cells, the effects of different concentrations of filtered, bacteria‐free, rotifer culture filtrate (RCF) on the growth and physiological parameters of Chlorella sp., and the response of Chlorella sp. at different starting cell densities to 10% RCF, were studied. The results show that RCF significantly decreased Chlorella cell densities during the incubation, suggesting that rotifers release some chemical(s) that inhibit microalgal cell growth. Chlorella cell densities decreased with increasing RCF concentration. Increasing the initial cell density of Chlorella dispersed the inhibitory chemical(s) present in 10% RCF over more cells, reducing their effect. The results confirm that the action of the chemical(s) released by rotifers on microalgal cell growth was dependent on both the RCF concentration and the exposure time. They also demonstrate that ≥10% RCF significantly inhibited photosynthesis and respiration, which would account for some of the decreased Chlorella cell growth in the presence of RCF. Calculations based on the data indicate that the rotifer‐derived chemical(s) released hourly from each rotifer inhibits growth by 45.5 microalgal cells in addition to the rotifer predation, with a 48 h LC50 value of 18.8% RCF. Based on these results, fresh medium instead of the old culture medium was contaminated by the rotifers. [ABSTRACT FROM AUTHOR]

The domesticated marine microalga Diacronema lutheri is of great interest for producing various highly valuable molecules like lipids, particularly long‐chain polyunsaturated fatty acids (LC‐PUFA). In this study, we investigated the impact of phosphorus (P) and nitrogen (N) starvation on growth, carbon fixation (photosynthetic activity) and partitioning, and membrane lipid remodeling in this alga during batch culture. Our results show that the photosynthetic machinery was similarly affected by P and N stress. Under N starvation, we observed a much lower photosynthetic rate and biomass productivity. The degradation and re‐use of cellular N‐containing compounds contributed to triacylglycerol (TAG) accumulation. On the other hand, P‐starved cells maintained pigment content and a carbon partitioning pattern more similar to the control, ensuring a high biomass. Betaine lipids constitute the major compounds of non‐plastidial membranes, which are rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Under P and N starvations, EPA was transferred from the recycling of membrane polar lipids, most likely contributing to TAG accumulation. [ABSTRACT FROM AUTHOR]