Past model studies have projected a global decrease in marine net primary production (NPP) over the 21st century, but these studies focused on the multi-model mean rather than on the large ...inter-model differences. Here, we analyze model-simulated changes in NPP for the 21st century under IPCC's high-emission scenario RCP8.5. We use a suite of nine coupled carbon–climate Earth system models with embedded marine ecosystem models and focus on the spread between the different models and the underlying reasons. Globally, NPP decreases in five out of the nine models over the course of the 21st century, while three show no significant trend and one even simulates an increase. The largest model spread occurs in the low latitudes (between 30° S and 30° N), with individual models simulating relative changes between −25 and +40 %. Of the seven models diagnosing a net decrease in NPP in the low latitudes, only three simulate this to be a consequence of the classical interpretation, i.e., a stronger nutrient limitation due to increased stratification leading to reduced phytoplankton growth. In the other four, warming-induced increases in phytoplankton growth outbalance the stronger nutrient limitation. However, temperature-driven increases in grazing and other loss processes cause a net decrease in phytoplankton biomass and reduce NPP despite higher growth rates. One model projects a strong increase in NPP in the low latitudes, caused by an intensification of the microbial loop, while NPP in the remaining model changes by less than 0.5 %. While models consistently project increases NPP in the Southern Ocean, the regional inter-model range is also very substantial. In most models, this increase in NPP is driven by temperature, but it is also modulated by changes in light, macronutrients and iron as well as grazing. Overall, current projections of future changes in global marine NPP are subject to large uncertainties and necessitate a dedicated and sustained effort to improve the models and the concepts and data that guide their development.
Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or ...develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism. Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy. Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive ...esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long‐term PPI use, particularly at higher plasma concentrations.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Adult obesity is linked to asthma cases and is estimated to lead to 250 000 new cases yearly. Similar incidence and attributable risk (AR) estimates have not been developed for children. We sought to ...describe the relationship between overweight and obesity and incident asthma in childhood and quantify AR statistics in the United States for overweight and obesity on pediatric asthma.
The PEDSnet clinical data research network was used to conduct a retrospective cohort study (January 2009-December 2015) to compare asthma incidence among overweight and/or obese versus healthy weight 2- to 17-year-old children. Asthma incidence was defined as ≥2 encounters with a diagnosis of asthma and ≥1 asthma controller prescription. Stricter diagnostic criteria involved confirmation by spirometry. We used multivariable Poisson regression analyses to estimate incident asthma rates and risk ratios and accepted formulas for ARs.
Data from 507 496 children and 19 581 972 encounters were included. The mean participant observation period was 4 years. The adjusted risk for incident asthma was increased among children who were overweight (relative risk RR: 1.17; 95% confidence interval CI: 1.10-1.25) and obese (RR: 1.26; 95% CI: 1.18-1.34). The adjusted risk for spirometry-confirmed asthma was increased among children with obesity (RR: 1.29; 95% CI: 1.16-1.42). An estimated 23% to 27% of new asthma cases in children with obesity is directly attributable to obesity. In the absence of overweight and obesity, 10% of all cases of asthma would be avoided.
Obesity is a major preventable risk factor for pediatric asthma.
Abstract Extracorporeal membrane oxygenation (ECMO) provides days to weeks of support for patients with respiratory, cardiac, or combined cardiopulmonary failure. Since ECMO was first reported in ...1974, nearly 70,000 runs of ECMO have been implemented, and the use of ECMO in adults increased by more than 400% from 2006 to 2011 in the United States. A variety of factors, including the 2009 influenza A epidemic, results from recent clinical trials, and improvements in ECMO technology, have motivated this increased use in adults. Because ECMO is increasingly becoming available to a diverse population of critically ill patients, we provide an overview of its fundamental principles and a systematic review of the evidence basis of this treatment modality for a variety of indications in adults.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Global climate change is predicted to alter the ocean's biological productivity. But how will we recognise the impacts of climate change on ocean productivity? The most comprehensive information ...available on its global distribution comes from satellite ocean colour data. Now that over ten years of satellite-derived chlorophyll and productivity data have accumulated, can we begin to detect and attribute climate change-driven trends in productivity? Here we compare recent trends in satellite ocean colour data to longer-term time series from three biogeochemical models (GFDL, IPSL and NCAR). We find that detection of climate change-driven trends in the satellite data is confounded by the relatively short time series and large interannual and decadal variability in productivity. Thus, recent observed changes in chlorophyll, primary production and the size of the oligotrophic gyres cannot be unequivocally attributed to the impact of global climate change. Instead, our analyses suggest that a time series of ~40 years length is needed to distinguish a global warming trend from natural variability. In some regions, notably equatorial regions, detection times are predicted to be shorter (~20–30 years). Analysis of modelled chlorophyll and primary production from 2001–2100 suggests that, on average, the climate change-driven trend will not be unambiguously separable from decadal variability until ~2055. Because the magnitude of natural variability in chlorophyll and primary production is larger than, or similar to, the global warming trend, a consistent, decades-long data record must be established if the impact of climate change on ocean productivity is to be definitively detected.
We use a suite of eight ocean biogeochemical/ecological general circulation models from the Marine Ecosystem Model Intercomparison Project and Coupled Model Intercomparison Project Phase 5 archives ...to explore the relative roles of changes in winds (positive trend of Southern Annular Mode, SAM) and in warming‐ and freshening‐driven trends of upper ocean stratification in altering export production and CO2 uptake in the Southern Ocean at the end of the 21st century. The investigated models simulate a broad range of responses to climate change, with no agreement on a dominance of either the SAM or the warming signal south of 44°S. In the southernmost zone, i.e., south of 58°S, they concur on an increase of biological export production, while between 44 and 58°S the models lack consensus on the sign of change in export. Yet in both regions, the models show an enhanced CO2 uptake during spring and summer. This is due to a larger CO2(aq) drawdown by the same amount of summer export production at a higher Revelle factor at the end of the 21st century. This strongly increases the importance of the biological carbon pump in the entire Southern Ocean. In the temperate zone, between 30 and 44°S, all models show a predominance of the warming signal and a nutrient‐driven reduction of export production. As a consequence, the share of the regions south of 44°S to the total uptake of the Southern Ocean south of 30°S is projected to increase at the end of the 21st century from 47 to 66% with a commensurable decrease to the north. Despite this major reorganization of the meridional distribution of the major regions of uptake, the total uptake increases largely in line with the rising atmospheric CO2. Simulations with the MITgcm‐REcoM2 model show that this is mostly driven by the strong increase of atmospheric CO2, with the climate‐driven changes of natural CO2 exchange offsetting that trend only to a limited degree (∼10%) and with negligible impact of climate effects on anthropogenic CO2 uptake when integrated over a full annual cycle south of 30°S.
Key Points
Increase of CO2 uptake driven by anthropogenic carbon, not by climate change
A higher Revelle factor causes enhanced biologically driven CO2 uptake in summer
The southern Southern Ocean becomes more important for total CO2 uptake
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
CONTEXT Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled ...corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control. OBJECTIVE To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. DESIGN, SETTING, AND PARTICIPANTS The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization. INTERVENTION Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157). MAIN OUTCOME MEASURES The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control. RESULTS The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, −0.1 to 0.1 L), asthma-related quality of life (−0.1; 95% CI, −0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 95% CI, 1.1-1.6). CONCLUSION In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00442013
Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total ...of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10−12), a locus on chromosome 10p14 (P = 1.79 × 10−15) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10−13). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10−23), which is close to rs2070600, a SNP previously reported for association with FEV1/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Past studies of asthma in overweight/obese children have been inconsistent. The reason overweight/obese children commonly report worse asthma control remains unclear. Objective To ...determine qualitative differences in symptoms between lean and overweight/obese children with early-onset, atopic asthma. Methods We conducted a cross-sectional analytic study of lean (20% to 65% body mass index) and overweight/obese (≥85% body mass index) 10- to 17-year-old children with persistent, early-onset asthma. Participants completed 2 to 3 visits to provide a complete history, qualitative and quantitative asthma symptom characterization, and lung function testing. We determined associations between weight status and symptoms using multivariable linear and logistic regression methods. Results Overweight/obese and lean asthmatic children displayed similar lung function. Despite lower fraction of exhaled nitric oxide (30.0 vs 62.6 ppb; P = .037) and reduced methacholine responsiveness (PC20 FEV1 1.87 vs 0.45 mg/mL; P < .012), overweight/obese children reported more than thrice frequent rescue treatments (3.7 vs 1.1 treatments/wk; P = .0002) than did lean children. Weight status affected the child's primary symptom reported with loss of asthma control (Fisher exact test; P = .003); overweight/obese children more often reported shortness of breath (odds ratio = 11.8; 95% CI, 1.41-98.7) and less often reported cough (odds ratio = 0.26; 95% CI, 0.08-0.82). Gastroesophageal reflux scores were higher in overweight/obese children (9.6 vs 23.2; P = .003) and appear to mediate overweight/obesity-related asthma symptoms. Conclusions Overweight/obese children with early-onset asthma display poorer asthma control and a distinct pattern of symptoms. Greater shortness of breath and β-agonist use appears to be partially mediated via esophageal reflux symptoms. Overweight children with asthma may falsely attribute exertional dyspnea and esophageal reflux to asthma, leading to excess rescue medication use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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