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Eastern boundary upwelling systems (EBUS) contribute a disproportionate fraction of the global fish catch relative to their size and are especially susceptible to global environmental change. Here we present the evolution of communities over 50 d in an in situ mesocosm 6 km offshore of Callao, Peru, and in the nearby unenclosed coastal Pacific Ocean. The communities were monitored using multi-marker environmental DNA (eDNA) metabarcoding and flow cytometry. DNA extracted from weekly water samples were subjected to amplicon sequencing for four genetic loci: (1) the V1–V2 region of the 16S rRNA gene for photosynthetic eukaryotes (via their chloroplasts) and bacteria; (2) the V9 region of the 18S rRNA gene for exploration of eukaryotes but targeting phytoplankton; (3) cytochrome oxidase I (COI) for exploration of eukaryotic taxa but targeting invertebrates; and (4) the 12S rRNA gene, targeting vertebrates. The multi-marker approach showed a divergence of communities (from microbes to fish) between the mesocosm and the unenclosed ocean. Together with the environmental information, the genetic data furthered our mechanistic understanding of the processes that are shaping EBUS communities in a changing ocean. The unenclosed ocean experienced significant variability over the course of the 50 d experiment, with temporal shifts in community composition, but remained dominated by organisms that are characteristic of high-nutrient upwelling conditions (e.g., diatoms, copepods, anchovies). A large directional change was found in the mesocosm community. The mesocosm community that developed was characteristic of upwelling regions when upwelling relaxes and waters stratify (e.g., dinoflagellates, nanoflagellates). The selection of dinoflagellates under the salinity-driven experimentally stratified conditions in the mesocosm, as well as the warm conditions brought about by the coastal El Niño, may be an indication of how EBUS will respond under the global environmental changes (i.e., increases in surface temperature and freshwater input, leading to increased stratification) forecast by the IPCC.

Asthma; Asthma worsening; Eosinophilic asthma Asma; Empitjorament de l'asma; Asma eosinofílica Asma; Empeoramiento del asma; Asma eosinofílica Background Prostaglandin D2 receptor 2 (DP2) antagonists inhibit prostaglandin D2-induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist. Research Question What is the effect of the DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma? Study Design and Methods In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/μL. Patients aged ≥ 18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment. Results A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg. Interpretation Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury. This work was supported by GB001, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

A large-volume mesocosm-based nutrient perturbation experiment was conducted off the island of Hawai‘i, USA, to investigate the response of surface ocean phytoplankton communities to the addition of macronutrients, trace metals, and vitamins and to assess the feasibility of using mesocosms in the open ocean. Three free-drifting mesocosms (~60 m3) were deployed: one mesocosm served as a control (no nutrient amendments); a second (termed +P) was amended with nitrate (N), silicate (Si), phosphate (P), and a trace metal + vitamin mixture; and a third (termed -P) was amended with N, Si, and a trace metal + vitamin mixture but no P. These mesocosms were unreplicated due to logistical constraints and hence differences between treatments are qualitative. After 6 d, the largest response of the phytoplankton community was observed in the +P mesocosm, where chlorophyll a and 14C-based primary production were 2-3× greater than in the -P mesocosm and 4-6× greater than in the control. Comparison between mesocosm and ‘microcosm’ incubations (20 l) revealed differences in the magnitude and timing of production and marked differences in community structure with a reduced response of diatoms in microcosm treatments. Notably, we also observed pronounced declines in Prochlorococcus populations in all treatments, although these were greater in microcosms (up to 99%). Overall, this study confirmed the feasibility of deploying free-drifting mesocosms in the open ocean as a potentially powerful tool to investigate ecological impacts of nutrient perturbations and constitutes a valuable first step towards scaling plankton manipulation experiments.

Reynold A Panettieri Jr,1 Carlos A Camargo Jr,2 Tariq Cheema,3 Sherif G El Bayadi,4 Stanley Fiel,5 Tania M Vila,6 Renu G Jain,6 Dawn Midwinter,7 Byron Thomashow,8 Andrea Ludwig-Sengpiel,9 David A Lipson10,11 1Child Health Institute of New Jersey, Rutgers University School of Medicine, New Brunswick, NJ, USA; 2Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Breathing Disorder Center, Allegheny Health Network, Pittsburgh, PA, USA; 4Department of Medicine, St. Joseph’s Health/SUNY Upstate, Syracuse, NY, USA; 5Atlantic Health Systems/Morristown Medical Center, Morristown, NJ, 07960, USA; 6GSK, Research Triangle Park, NC, USA; 7GSK, Brentford, UK; 8Department of Medicine, Columbia University Medical Center, New York, NY, USA; 9KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany; 10Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 11GSK, Collegeville, PA, USACorrespondence: Reynold A Panettieri Jr, Rutgers University School of Medicine, 89 French Street, Suite 4210, New Brunswick, NJ, 08901, USA, Tel +1 732-235-6404, Email rp856@rbhs.rutgers.eduBackground: In the FULFIL trial, once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) resulted in reduced moderate/severe exacerbation rates and conferred significant improvements in lung function and health status in patients with chronic obstructive pulmonary disease (COPD) versus twice-daily budesonide/formoterol (BUD/FOR) dual therapy.Methods: FULFIL was a Phase III, randomized, double-blind, double-dummy, parallel-group study. Patients ≥ 40 years of age with symptomatic COPD were randomized 1:1 to FF/UMEC/VI 100/62.5/25 mcg or BUD/FOR 400/12 mcg. In this post hoc analysis, patients were categorized by exacerbation history in the year prior to study entry (≥ 1 moderate/severe exacerbation [recent exacerbation] versus no recent exacerbation). Endpoints included annual rate of on-treatment moderate/severe exacerbations up to Week 24, annual rate of on-treatment severe exacerbations up to Week 24, change from baseline in trough forced expiratory volume in 1 second at Week 24, and change from baseline in health status as measured by St George’s respiratory questionnaire total score at Week 24.Results: Of the 1810 patients in the intent-to-treat population, 1180 (65%) had one or more moderate/severe exacerbation in the year prior to entry, while 630 (35%) patients did not. FF/UMEC/VI versus BUD/FOR significantly reduced moderate/severe exacerbation rates in the recent exacerbation subgroup (mean annualized rate: 0.19 vs 0.29; rate ratio [95% confidence interval [CI]]: 0.64: [0.45, 0.91]; p=0.014) and numerically reduced moderate/severe exacerbation rates in the no recent exacerbation subgroup (mean annualized rate: 0.29 vs 0.43; rate ratio [95% CI]: 0.67 [0.43, 1.04]; p=0.073). Severe exacerbation rates were numerically reduced with FF/UMEC/VI versus BUD/FOR treatment across both subgroups. FF/UMEC/VI conferred significant improvements in lung function and health status versus BUD/FOR, regardless of recent exacerbation history.Conclusion: FF/UMEC/VI reduced moderate/severe and severe exacerbation rates and improved lung function and health status versus BUD/FOR in patients with symptomatic COPD, regardless of recent exacerbation history.Keywords: COPD, exacerbations, severe exacerbations, triple therapy, ICS/LABA

International audience; BackgroundAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with changes in the sputum microbiome, including an increased prevalence of pathogenic bacteria. Vaccination against the most frequent bacteria identified in AECOPD might reduce exacerbation frequency. We assessed the efficacy, safety, and immunogenicity of a candidate vaccine containing surface proteins from non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) in patients with COPD.MethodsThis multicentre, randomised, observer-blinded, placebo-controlled, proof-of-concept, phase 2b trial recruited patients with stable COPD, moderate-to-very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2, 3, or 4), at 67 clinical sites in Belgium, Canada, France, Germany, Italy, Spain, UK, and USA. Eligible patients were aged 40–80 years and had a history of at least one moderate or severe exacerbation in the previous year. Patients were allocated (1:1) using a minimisation algorithm to receive two intramuscular injections of NTHi–Mcat vaccine or placebo 60 days apart, in addition to standard care. The allocation algorithm considered age category, number of previous exacerbations, COPD severity at study entry, and country as minimisation factors, to guarantee treatment balance within each factor. Vaccine recipients and those responsible for evaluating study endpoints were masked to group allocation. In the analysis of efficacy, the primary outcome was the rate of any moderate or severe AECOPD occurring within a 1-year period, starting 1 month after the second dose in patients who received two vaccine doses (modified total vaccinated cohort). Safety was assessed in the total vaccinated cohort. The trial is registered with ClinicalTrials.gov, number NCT03281876, and is complete.FindingsBetween Nov 27, 2017, and Nov 30, 2018, 606 adults were enrolled and included in the total vaccinated cohort (304 in the NTHi–Mcat vaccine group, 302 in the placebo group); 571 received two doses and were included in the primary efficacy analysis (279 in the NTHi–Mcat vaccine group, 292 in the placebo group). 23 participants dropped-out in the NTHi–Mcat vaccine group and 39 in the placebo group; this included 4 patients in the NTHi–Mcat vaccine group and 15 in the placebo group who withdrew from the study because of an adverse event. The primary analysis included 340 exacerbations (in follow-up time 102 123 days) in the NTHi–Mcat vaccine group and 333 (in 104 443 days) in the placebo group, with a yearly rate of moderate or severe AECOPD of 1·22 in the NTHi–Mcat vaccine group and 1·17 in the placebo group, with vaccine efficacy in reducing the yearly rate of moderate or severe AECOPD estimated to be zero (vaccine efficacy point estimate 2·26% [87% CI –18·27 to 11·58]; p=0·82). Solicited local adverse events were more frequent in the NTHi–Mcat vaccine group (216 [72%] of 301 patients) than with placebo (34 [11%] of 299 patients), and the frequency of solicited general adverse events was similar between groups (239 [79%] of 301 vs 235 [79%] of 299 patients). There was one death in the NTHi–Mcat vaccine group (acute respiratory failure, not related to vaccination) and ten in the placebo group (seven due in part to COPD or respiratory failure). There were 158 serious adverse events (89 [29%] of 304 patients) in the NTHi–Mcat vaccine group, not related to vaccination, and 214 (99 [33%] of 302 patients) in the placebo group.InterpretationNTHi–Mcat vaccine administered to patients with COPD did not show efficacy in reducing the yearly rate of moderate or severe exacerbations. No safety concerns were identified.

Prostaglandin DWhat is the effect of the DPIn this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/μL. Patients aged ≥ 18 years to 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment.A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg.Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury.ClinicalTrials.gov; No.: NCT03683576; URL: www.gov.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. SOURCE evaluated the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma.We conducted this phase 3, multicentre, randomised, double-blind, placebo-controlled study across 60 sites in seven countries. Participants aged 18-80 years with physician-diagnosed asthma, who had been receiving medium-dose or high-dose inhaled corticosteroids and had at least one asthma exacerbation in the 12 months before screening were eligible. Patients who were receiving medium-dose inhaled corticosteroids must have had their dose increased to a high dose for at least 3 months before screening. After an oral corticosteroid optimisation phase of up to 8 weeks, participants were randomly assigned according to a computer-generated fixed block randomisation sequence to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks during a 48 week treatment period (4 week induction phase, 36 week oral corticosteroid reduction phase, and 8 week maintenance phase). Randomisation was stratified by region. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoint was the categorised percentage reduction from baseline in daily oral corticosteroid dose at week 48 without the loss of asthma control. Efficacy and safety endpoints were assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03406078.Between March 5, 2018, and Sept 27, 2019, 150 participants were randomly assigned to receive tezepelumab 210 mg (n=74) or placebo (n=76). The cumulative odds of achieving a category of greater percentage reduction in an oral corticosteroid dose for daily maintenance at week 48 were similar with tezepelumab or placebo in the overall population (odds ratio [OR] 1·28 [95% CI 0·69-2·35], p=0·43; the primary endpoint was not met). The cumulative odds were higher with tezepelumab than with placebo in participants with baseline blood eosinophil counts of at least 150 cells per μL (2·58 [1·16-5·75]), but not in participants with counts below 150 cells per μL (0·40 [0·14-1·13]). Tezepelumab was well tolerated, with no safety concerns identified. 53 (72%) of 74 tezepelumab-assigned participants and 65 (86%) of 76 placebo-assigned participants reported an adverse event. Serious adverse events were reported in 12 (16%) participants in the tezepelumab group and 16 (21%) participants in the placebo group.We did not observe a significant improvement in oral corticosteroid dose reduction with tezepelumab versus placebo in the overall population of this oral corticosteroid-sparing study, although an improvement was observed in participants with baseline blood eosinophil counts of at least 150 cells per μL.AstraZeneca and Amgen.

Upwelling of nutrient-rich deep waters make eastern boundary upwelling systems (EBUSs), such as the Humboldt Current system, hot spots of marine productivity. Associated settling of organic matter to depth and consecutive aerobic decomposition results in large subsurface water volumes being oxygen depleted. Under these circumstances, organic matter remineralisation can continue via denitrification, which represents a major loss pathway for bioavailable nitrogen. Additionally, anaerobic ammonium oxidation can remove significant amounts of nitrogen in these areas. Here we assess the interplay of suboxic water upwelling and nitrogen cycling in a manipulative offshore mesocosm experiment. Measured denitrification rates in incubations with water from the oxygen-depleted bottom layer of the mesocosms (via 15N label incubations) mostly ranged between 5.5 and 20 nmol N2 L−1 h−1 (interquartile range), reaching up to 80 nmol N2 L−1 h−1. However, actual in situ rates in the mesocosms, estimated via Michaelis–Menten kinetic scaling, did most likely not exceed 0.2–4.2 nmol N2 L−1 h−1 (interquartile range) due to substrate limitation. In the surrounding Pacific, measured denitrification rates were similar, although indications of substrate limitation were detected only once. In contrast, anammox (anaerobic ammonium oxidation) made only a minor contribution to the overall nitrogen loss when encountered in both the mesocosms and the Pacific Ocean. This was potentially related to organic matter C / N stoichiometry and/or process-specific oxygen and hydrogen sulfide sensitivities. Over the first 38 d of the experiment, total nitrogen loss calculated from in situ rates of denitrification and anammox was comparable to estimates from a full nitrogen budget in the mesocosms and ranged between ∼ 1 and 5.5 µmol N L−1. This represents up to ∼ 20 % of the initially bioavailable inorganic and organic nitrogen standing stocks. Interestingly, this loss is comparable to the total amount of particulate organic nitrogen that was exported into the sediment traps at the bottom of the mesocosms at about 20 m depth. Altogether, this suggests that a significant portion, if not the majority of nitrogen that could be exported to depth, is already lost, i.e. converted to N2 in a relatively shallow layer of the surface ocean, provided that there are oxygen-deficient conditions like those during coastal upwelling in our study. Published data for primary productivity and nitrogen loss in all EBUSs reinforce such conclusion.

Background Inhaled bronchodilator therapy is currently the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Some inhalers require patients to achieve certain inhalation efforts either to activate the device or to deliver medication to the site of action. For dry powder inhalers, low peak inspiratory flow (PIF) can result in poor medication delivery but the clinical significance of this is not well understood. Methods TRONARTO was a 4-week, randomized, double-blind, placebo-controlled, multicenter, parallel-group study which stratified patients with moderate-to-severe COPD according to their PIF against medium-low resistance at screening. Patients were randomized to receive tiotropium/olodaterol (5 μg/5 μg) or matched placebo delivered via the Respimat® Soft Mist™ inhaler (SMI). After 4 weeks of treatment, we assessed change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0–3 hours (FEV1 AUC0–3h) and trough FEV1. Results Overall, 213 patients were randomized, of whom 106 received tiotropium/olodaterol (PIF, Graphical Abstract

Upwelling of nutrient-rich deep waters make Eastern Boundary upwelling systems (EBUS), such as the Humboldt Current System, hotspots of marine productivity. Associated settling of organic matter to depth and consecutive aerobic de composition results in large sub-surface water volumes being oxygen-depleted. Under these circumstances organic matter remineralisation can continue via denitrification which represents a major loss pathway of bioavailable nitrogen. Another process removing significant amounts of nitrogen in these areas is anaerobic ammonium oxidation. Here we assess the interplay of suboxic water upwelling and nitrogen cycling in a manipulative off-shore mesocosm experiment. Measured denitrification rates in the oxygen-depleted bottom layer of the mesocosms mostly ranged between 5.5–20 (interquartile range), reaching up to 80 nmol N2 L−1 h−1. However, realised in-situ rates did most likely not exceed 0.6–1.6 nmol N2 L−1 h−1 (interquartile range), due to substrate limitation in the mesocosms. This was in contrast to realised rates in the surrounding Pacific. Both in the mesocosms and the Pacific Ocean anammox made only a minor contribution to overall nitrogen loss when encountered. Over the first 38 days of the experiment, total nitrogen loss calculated from denitrification and anammox rates was comparable to estimates from a full nitrogen budget in the mesocosms and ranged between ∼ 2–6 μmol N L−1. This represents up to ∼ 20 % of the initially bioavailable inorganic and organic nitrogen standing stocks. Interestingly, this loss is comparable to the total amount of particulate organic nitrogen that was exported into the sediment traps at the bottom of the mesocosms in about 20 metres depth. Altogether, this suggests that a significant portion, if not the majority of nitrogen that could be exported to depth, is already lost, i.e. converted to N2 in a relatively shallow layer of the surface ocean, provided oxygen-deficient conditions like during coastal upwelling in our study.

Wie bereits in Abschn. 3.4 dargelegt, bilden die zwolf Wirkfaktoren der Organisationskultur nach Sackmann eine der theoretischen Grundlagen fur dieses Praxisbuch. Anhand dieser Faktoren kann eine Organisation bzw. ihre Kultur betrachtet werden. Die Autorinnen wenden in diesem Kapitel diese Wirkfaktoren speziell auf soziale Organisationen an (Abb. 5.1). Dabei betrachten sie die Auswirkungen der Digitalisierung mit ihren Vorteilen als auch Herausforderungen anhand von ganz konkreten Praxisbeispielen. Den Schwerpunkt legen sie auf den Aspekt des Lernens, der Kommunikation und der Zusammenarbeit zur Entwicklung von Personal und Organisationen.

The oceans’ uptake of anthropogenic carbon dioxide (CO2) decreases seawater pH and alters the inorganic carbon speciation – summarized in the term ocean acidification (OA). Already today, coastal regions experience episodic pH events during which surface layer pH drops below values projected for the surface ocean at the end of the century. Future OA is expected to further enhance the intensity of these coastal extreme pH events. To evaluate the influence of such episodic OA events in coastal regions, we deployed eight pelagic mesocosms for 53 days in Raunefjord, Norway, and enclosed 56–61 m3 of local seawater containing a natural plankton community under nutrient limited post-bloom conditions. Four mesocosms were enriched with CO2 to simulate extreme pCO2 levels of 1978 – 2069 μatm while the other four served as untreated controls. Here, we present results from multivariate analyses on OA-induced changes in the phyto-, micro-, and mesozooplankton community structure. Pronounced differences in the plankton community emerged early in the experiment, and were amplified by enhanced top-down control throughout the study period. The plankton groups responding most profoundly to high CO2 conditions were cyanobacteria (negative), chlorophyceae (negative), auto- and heterotrophic microzooplankton (negative), and a variety of mesozooplanktonic taxa, including copepoda (mixed), appendicularia (positive), hydrozoa (positive), fish larvae (positive), and gastropoda (negative). The restructuring of the community coincided with significant changes in the concentration and elemental stoichiometry of particulate organic matter. Results imply that extreme CO2 events can lead to a substantial reorganization of the planktonic food web, affecting multiple trophic levels from phytoplankton to primary and secondary consumers. Copyright © 2021 Spisla, Taucher, Bach, Haunost, Boxhammer, King, Jenkins, Wallace, Ludwig, Meyer, Stange, Minutolo, Lohbeck, Nauendorf, Kalter, Lischka, Sswat, Dörner, Ismar-Rebitz, Aberle, Yong, Bouquet, Lechtenbörger, Kohnert, Krudewig and Riebesell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

In diesem Kapitel werden in kurzer Form die verschiedenen Ansatze und Modelle vorgestellt, die wegweisend fur die Entwicklung der Betrachtung der Organisationskultur sind. Sie bieten damit den theoretischen Hintergrund fur die eingesetzten Methoden im Fortgang dieses Buches. Vor diesem Hintergrund wird uber gelingende Veranderungsprozesse berichtet, um Handlungsoptionen aufzuzeigen. Es werden Methoden zur Messung von Organisationskultur beschrieben. Besonderes Augenmerk wird auf die Arbeit mit Werten gelegt, da sie die Organisationskultur wesentlich bestimmen. Bezugnehmend auf Frau Prof. Sackmann wird die Wechselwirkung von Erfolgsfaktoren der Organisation und verschiedenen Kulturfaktoren dargestellt.

Die Sozialwirtschaft hat in den letzten Jahren eine ganze Reihe an nennenswerten und damit systemrelevanten Veranderungen der Rahmenbedingungen durchlaufen. Die Autorinnen zeigen drei der ihrer Meinung nach besonders relevanten Faktoren auf: die neue Generation an Arbeiternehmer*innen auf dem Arbeitsmarkt, besonders relevante Anderungen in den rechtlichen Grundlagen sowie die Digitalisierung und ihre besondere Dynamik. Diese Faktoren beeinflussen masgeblich die Personal- und Organisationsentwicklung in den Organisationen und sollten in Veranderungsprozessen mindestens mitgedacht und idealerweise proaktiv einbezogen werden.

Organisationen und Unternehmen stehen derzeit vor gravierenden Herausforderungen, um sich zukunftsfahig aufzustellen beziehungsweise zu bleiben. Dabei gibt es zwar Unterschiede zwischen Branchen, zwischen Stadt und Land, zwischen Klein- und Grosunternehmen, aber die grundsatzlichen Tendenzen sind fur alle gleich

In diesem Kapitel zeigen die Autorinnen anhand der Erfahrungen aus verschiedenen Praxisprojekten im Rahmen von Veranderungsprozessen die Chancen aber auch die Herausforderungen auf, denen soziale Organisationen im Zuge der digitalen Transformation begegnen konnen. Dabei legen sie den Schwerpunkt auf die Themenbereiche Lernen und Entwicklung, Kommunikation, Wissensmanagement sowie Zusammenarbeit in Organisationen. In den vier beispielhaften Projekten konnen die Leser*innen nutzliche Praxistipps einerseits und den strategischen Aufbau von Projekten in Veranderungsprozessen andererseits betrachten.

In diesem Kapitel mochten die Autorinnen die Leser*innen anhand von praktischen Tipps bei Veranderungsprozessen in Organisationen unterstutzen. Dabei nutzen sie die zusammengefassten Erkenntnisse aus den Kap. 4 und 5 und geben wichtige Tipps fur Veranderungsprozesse den Leser*innen an die Hand. Diese reichen von strategischen Voraussetzungen und Entscheidungen auf Seiten der Fuhrungsebene bis hin zu Instrumenten und Tools zur Integration und Motivation der Mitarbeiter*innen. Schlieslich wird anhand eines Coachingsprozesses gezeigt, welche Auswirkung das individuelle Lernen auf Veranderungsprozesse haben kann.

Ocean acidification, the change in seawater carbonate chemistry due to the uptake of anthropogenic CO2, affects the physiology of marine organisms in multiple ways1. Diverse competitive and trophic interactions transform the metabolic responses to changes in community composition, seasonal succession and potentially geographical distribution of species. The health of ocean ecosystems depends on whether basic biotic functions are maintained, ecosystem engineers and keystone species are retained, and the spread of nuisance species is avoided2. Here, we show in a field experiment that the toxic microalga Vicicitus globosus has a selective advantage under ocean acidification, increasing its abundance in natural plankton communities at CO2 levels higher than 600 µatm and developing blooms above 800 µatm CO2. The mass development of V. globosus has had a dramatic impact on the plankton community, preventing the development of the micro- and mesozooplankton communities, thereby disrupting trophic transfer of primary produced organic matter. This has prolonged the residence of particulate matter in the water column and caused a strong decline in export flux. Considering its wide geographical distribution and confirmed role in fish kills3, the proliferation of V. globosus under the IPCC4 CO2 emission representative concentration pathway (RCP4.5 to RCP8.5) scenarios may pose an emergent threat to coastal communities, aquaculture and fisheries. Ocean acidification will result in biological winners and losers. A mesocosm experiment shows that a toxic algal species is a winner under ocean acidification, with implications for the marine food web and, more generally, ecosystem services.

Background The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects. Objective We explored this data set to define type 2 inflammation based on airway mucosal IL-13–driven gene expression and how this related to clinically accessible biomarkers. Methods IL-13–driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression. Results Expression of airway mucosal CCL26, periostin, and IL-13–IVS all facilitated segregation of subjects into type 2–high and type 2–low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm 3 ) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26–high status. Clinical variables did not differ between subjects with type 2–high and type 2–low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression. Conclusion A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13–IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient selection for novel type 2 therapeutics.

Rationale: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited.Objectives: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD.Methods: The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). A patient subgroup remained on blinded treatment for up to 52 weeks. Co–primary endpoints were change from baseline in trough FEV1 and in St. George’s Respiratory Questionnaire (SGRQ) total score at Week 24.Measurements and Main Results...

Eastern boundary upwelling systems (EBUS) are among the most productive marine ecosystems on Earth. The high productivity in surface waters is facilitated by upwelling of nutrient-rich deep waters, with high light availability enabling fast phytoplankton growth and nutrient utilization. However, there are numerous biotic and abiotic factors modifying productivity and biogeochemical processes. Determining these factors is important because EBUS are considered hotspots of climate change, and reliable predictions on their future functioning requires understanding of the mechanisms driving biogeochemical cycles therein. In this study, we used in situ mesocosms to obtain mechanistic understanding of processes controlling productivity, organic matter export, and particulate matter stoichiometry in the coastal Peruvian upwelling system. Therefore, eight mesocosm units with a volume of ~50 m3 were deployed for 50 days ~6 km off Callao during austral summer 2017, coinciding with a coastal El Niño event. To compare how upwelling of different water bodies influences plankton succession patterns, we collected two subsurface waters at different locations in the regional oxygen minimum zone (OMZ) and injected these into four replicate mesocosms, respectively (mixing ratio ≈ 1.5:1 mesocosm: OMZ water). The differences in nutrient concentrations between the collected water bodies were relatively small, and therefore we do not consider treatment differences in the present paper. The phytoplankton communities were initially dominated by diatoms but shifted towards a pronounced dominance of the mixotrophic harmful dinoflagellate (Akashiwo sanguinea) when inorganic nitrogen was exhausted in surface layers. The community shift resulted in a major short-term increase in productivity during A. sanguinea growth which left a pronounced imprint on organic matter C:N:P stoichiometry. However, C, N, and P export fluxes were not affected by this ecological regime shift because A. sanguinea persisted in the water column and did not sink out during the experiment. Accordingly, ongoing export fluxes during the study were maintained mainly by a remaining “background” plankton community. Overall, biogeochemical pools and fluxes were surprisingly constant in between the ecological regime shifts. We explain this constancy by light limitation through self-shading by phytoplankton and inorganic nitrogen limitation which constrained phytoplankton growth. Thus, gain and loss processes seemed to be relatively well balanced and there was little opportunity for blooms, which represents an event where the system becomes unbalanced. The mesocosm study revealed key links between ecological and biogeochemical processes for one of the economically most important regions in the oceans.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with poor outcomes. Iron is known to signal cellular responses, and its levels are regulated by lipocalin-2 (LCN2) expression, a PDAC pro-tumorigenic molecule. However, how iron and LCN2 function in PDAC is unclear. Here we demonstrate that iron levels regulate PDAC cell proliferation, invasion, expression of epithelial to mesenchymal tumor markers, and pro-inflammatory cytokines. Iron chelation increased the expression of the LCN2 receptorSLC22A17in pancreatic stellate cells and the anti-metastatic geneNDRG1in PDAC cells. Deletion ofLcn2in mouse tumor cells modulated the expression of genes involved in extracellular matrix deposition and cell migration. Moreover, cellular iron responses were dependent on theKrasmutation status of cells, andLCN2expression levels. Deletion ofLcn2expression in PDAC suggests a protective role against metastasis. Thus, iron modulation and LCN2 blockade could serve as potential therapeutic approaches against PDAC.

In the autumn of 2014, nine large mesocosms were deployed in the oligotrophic subtropical North-Atlantic coastal waters off Gran Canaria (Spain). Their deployment was designed to address the acidification effects of CO2 levels from 400 to 1,400 mu atm, on a plankton community experiencing upwelling of nutrient-rich deep water. Among other parameters, chlorophyll a (chl-a), potential respiration (Phi), and biomass in terms of particulate protein (B) were measured in the microplankton community (0.7-50.0 mu m) during an oligotrophic phase (Phase I), a phytoplankton-bloom phase (Phase II), and a post-bloom phase (Phase III). Here, we explore the use of the Phi/chl-a ratio in monitoring shifts in the microplankton community composition and its metabolism. Phi/chl-a values below 2.5 mu L O-2 h(-1) (mu g chl-a)(-1) indicated a community dominated by photoautotrophs. When Phi/chl-a ranged higher, between 2.5 and 7.0 mu L O-2 h(-1) (pg chl-a)(-1) , it indicated a mixed community of phytoplankton, microzooplankton and heterotrophic prokaryotes. When Phi/chl-a rose above 7.0 mu L O-2 h(-1) (mu g chl-a)(-1), it indicated a community where microzooplankton proliferated (>10.0 mu L O-2 h(-1) (mu g chl-a)(-1)), because heterotrophic dinoflagellates bloomed. The first derivative of B, as a function of time (dB/dt), indicates the rate of protein build-up when positive and the rate of protein loss, when negative. It revealed that the maximum increase in particulate protein (biomass) occurred between 1 and 2 days before the chl-a peak. A day after this peak, the trough revealed the maximum net biomass loss. This analysis did not detect significant changes in particulate protein, neither in Phase I nor in Phase III. Integral analysis of Phi/chl-a and B, over the duration of each phase, for each mesocosm, reflected a positive relationship between 4) and pCO(2) during Phase II [alpha = 230.10-5 mu L O-2 h(-1) L-1 (patm CO2)(-1) (phase-day)(-1), R-2 = 0.30] and between chl-a and pCO(2) during Phase III [alpha = 100.10(-5) Ag chl-a L-1 (mu atmCO(2))(-1) (phase-day)(-1), R-2 = 0.84]. At the end of Phase II, a harmful algal species (HAS), Vicicitus globosus, bloomed in the high pCO(2) mesocosms. In these mesocosms, microzooplankton did not proliferate, and chl-a retention time in the water column increased. In these V globosus-disrupted communities, the (Phi/chl-a ratio [4.1 +/- 1.5 /mu L O-2 h(-1) (mu g chl-a)(-1)] was more similar to the Phi/chl-a ratio in a mixed plankton community than to a photoautotroph-dominated one.

Background: Poor adherence is a key factor in poor asthma control. A connected inhaler system (CIS) comprising sensors on inhalers, a patient-facing app, and a Healthcare Professional (HCP) dashboard could improve asthma management by improving adherence. Methods: Study 207040 (NCT033800429) is one of the first to investigate the different elements of a CIS in improving adherence. The study had a 24-week, open-label, randomised, multi-centre, parallel group design with 5 treatment arms, in uncontrolled asthmatic patients [Asthma Control Test (ACT) Results: The primary endpoint was the effect of 6 months’ use of a CIS on adherence to maintenance therapy assessed over months 4-6, with the absolute adjusted mean adherence difference in arm 1 (data on maintenance to participant and HCP; 82.0%) being 13.2% (95% CI [6.3%, 20.0%]; p Conclusion: The study demonstrates that a CIS can improve adherence to maintenance medication for patients with uncontrolled asthma. Funding: GlaxoSmithKline plc. (207040)

ObjectivesAs tobacco companies can circumvent tax increases, a minimum retail price per-cigarette/per-gram of roll-your-own tobacco presents an additional mechanism for governments to reduce smoking. We examined (1) anticipated responses to a hypothetical minimum price-per-cigarette/per-gram among smokers in the UK; (2) what demographic and smoker characteristics are associated with anticipated responses; and (3) whether minimum pricing may help ex-smokers stay quit.DesignCross-sectional survey (May–July 2019).SettingUK.ParticipantsAdult cigarette smokers (n=2412) and ex-smokers (n=700).Main outcome measurementsAnticipated responses to a hypothetical minimum price of £10.00 for 20 cigarettes (£0.50 per-cigarette) and £13.50 for 30 grams of roll-your-own tobacco (£0.45 per-gram); approximately £0.10 per-cigarette/per-gram increases on the cheapest prices in leading UK supermarkets (January 2019). Smokers were presented with ten options (eg, ‘Try to quit’) and asked which they would do (Yes/No) and then which they would most likely do. Ex-smokers were asked to what extent the minimum prices would help them stay quit (A lot vs Lesser agreement).ResultsAmong smokers, 55.6% said they would most likely smoke the same amount, 10.7% they would smoke less, 9.5% they would try to quit and 5.8% they would use e-cigarettes more often. Anticipated reactions were associated with demography and smoker characteristics, for example, C2DE (lower social grade) smokers were less likely than ABC1 (higher social grade) smokers to say they would smoke the same as they do now (ORAdj=0.74, 95% CI 0.62 to 0.88). Among ex-smokers, 38.5% said the minimum prices would help them stay quit ‘A lot’, more so among C2DE than ABC1 participants (ORAdj=1.80, 95% CI 1.30 to 2.49).ConclusionsIn response to a hypothetical minimum price for cigarettes and roll-your-own tobacco, approximately a fifth of smokers in the UK indicated they would smoke less or quit and almost two-fifths of ex-smokers indicated the prices would help them stay quit.