ALPINE2:Efficacy and safety of 14-day vs 28-day inhaled aztreonam for <i>Pa </i>eradication in children with cystic fibrosis

Background: Antibiotic eradication therapies recommended for newly isolated Pseudomonas aeruginosa (Pa) in people with cystic fibrosis (pwCF) can be burdensome. ALPINE2 compared the efficacy and safety of a shortened 14-day course of aztreonam for inhalation solution (AZLI) with 28-day AZLI in paediatric pwCF. Methods: ALPINE2 (a double-blind, phase 3b study) included children aged 3 months to &lt;18 years with CF and new-onset Pa infection. Participants were randomized to receive 75 mg AZLI three times daily for either 28 or 14 days followed by 14 days' matched placebo. The primary endpoint was rate of primary Pa eradication (no Pa detected during the 4 weeks post AZLI treatment). Non-inferiority was achieved if the lower 95% CI bound of the treatment difference between the two arms was above −20%. Secondary endpoints included assessments of Pa recurrence during 108 weeks of follow-up after primary eradication. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In total, 149 participants were randomized (14-day AZLI, n = 74; 28-day AZLI, n = 75) and 142 (95.3%) completed treatment. Median age: 6.0 years (range: 0.3–17.0). Baseline characteristics were similar between treatment arms. Primary Pa eradication rates: 14-day AZLI, 55.9%; 28-day AZLI, 63.4%; treatment difference (CI), −8.0% (−24.6, 8.6%). Pa recurrence rates at follow-up end: 14-day AZLI, 54.1% (n = 20/37); 28-day AZLI, 41.9% (n = 18/43). TEAEs were similar between treatment arms. No new safety signals were observed. Conclusions: Non-inferiority of 14-day AZLI versus 28-day AZLI was not demonstrated. Both courses were well tolerated, further supporting AZLI short-term safety in paediatric and adolescent pwCF. ClinicalTrials.gov:</p

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Ontology learning from open linked data and Web snippets

The Web of Open Linked Data (OLD) is a recommended best practice for exposing, sharing, and connecting pieces of data, information, and knowledge on the Semantic Web using URIs and RDF. Such data can be used as a training source for ontology learning from web textual contents in order to bridge the gap between structured data and the Web. In this paper, we propose a new method of ontology learning that consists in learning linguistic patterns related to OLD entities attributes from web snippets. Our insight is to use the Linked Data as a skeleton for ontology construction and for pattern learning from texts. The contribution resides on learning patterns for relations existing in the Web of Linked Data from Web content. These patterns are used to populate the ontology core schema with new entities and attributes values. The experiments of the proposal have shown promising results in precision

Persistent El Niño driven shifts in marine cyanobacteria populations.

In the California Current Ecosystem, El Niño acts as a natural phenomenon that is partially representative of climate change impacts on marine bacteria at timescales relevant to microbial communities. Between 2014-2016, the North Pacific warm anomaly (a.k.a., the "blob") and an El Niño event resulted in prolonged ocean warming in the Southern California Bight (SCB). To determine whether this "marine heatwave" resulted in shifts in microbial populations, we sequenced the rpoC1 gene from the biogeochemically important picocyanobacteria Prochlorococcus and Synechococcus at 434 time points from 2009-2018 in the MICRO time series at Newport Beach, CA. Across the time series, we observed an increase in the abundance of Prochlorococcus relative to Synechococcus as well as elevated frequencies of ecotypes commonly associated with low-nutrient and high-temperature conditions. The relationships between environmental and ecotype trends appeared to operate on differing temporal scales. In contrast to ecotype trends, most microdiverse populations were static and possibly reflect local habitat conditions. The only exceptions were microdiversity from Prochlorococcous HLI and Synechococcus Clade II that shifted in response to the 2015 El Niño event. Overall, Prochlorococcus and Synechococcus populations did not return to their pre-heatwave composition by the end of this study. This research demonstrates that extended warming in the SCB can result in persistent changes in key microbial populations

Persistent El Niño driven shifts in marine cyanobacteria populations.

In the California Current Ecosystem, El Niño acts as a natural phenomenon that is partially representative of climate change impacts on marine bacteria at timescales relevant to microbial communities. Between 2014-2016, the North Pacific warm anomaly (a.k.a., the "blob") and an El Niño event resulted in prolonged ocean warming in the Southern California Bight (SCB). To determine whether this "marine heatwave" resulted in shifts in microbial populations, we sequenced the rpoC1 gene from the biogeochemically important picocyanobacteria Prochlorococcus and Synechococcus at 434 time points from 2009-2018 in the MICRO time series at Newport Beach, CA. Across the time series, we observed an increase in the abundance of Prochlorococcus relative to Synechococcus as well as elevated frequencies of ecotypes commonly associated with low-nutrient and high-temperature conditions. The relationships between environmental and ecotype trends appeared to operate on differing temporal scales. In contrast to ecotype trends, most microdiverse populations were static and possibly reflect local habitat conditions. The only exceptions were microdiversity from Prochlorococcous HLI and Synechococcus Clade II that shifted in response to the 2015 El Niño event. Overall, Prochlorococcus and Synechococcus populations did not return to their pre-heatwave composition by the end of this study. This research demonstrates that extended warming in the SCB can result in persistent changes in key microbial populations

Persistent El Niño driven shifts in marine cyanobacteria populations.

In the California Current Ecosystem, El Niño acts as a natural phenomenon that is partially representative of climate change impacts on marine bacteria at timescales relevant to microbial communities. Between 2014-2016, the North Pacific warm anomaly (a.k.a., the "blob") and an El Niño event resulted in prolonged ocean warming in the Southern California Bight (SCB). To determine whether this "marine heatwave" resulted in shifts in microbial populations, we sequenced the rpoC1 gene from the biogeochemically important picocyanobacteria Prochlorococcus and Synechococcus at 434 time points from 2009-2018 in the MICRO time series at Newport Beach, CA. Across the time series, we observed an increase in the abundance of Prochlorococcus relative to Synechococcus as well as elevated frequencies of ecotypes commonly associated with low-nutrient and high-temperature conditions. The relationships between environmental and ecotype trends appeared to operate on differing temporal scales. In contrast to ecotype trends, most microdiverse populations were static and possibly reflect local habitat conditions. The only exceptions were microdiversity from Prochlorococcous HLI and Synechococcus Clade II that shifted in response to the 2015 El Niño event. Overall, Prochlorococcus and Synechococcus populations did not return to their pre-heatwave composition by the end of this study. This research demonstrates that extended warming in the SCB can result in persistent changes in key microbial populations

ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis.

Antibiotic eradication therapies recommended for newly isolated Pseudomonas aeruginosa (Pa) in people with cystic fibrosis (pwCF) can be burdensome. ALPINE2 compared the efficacy and safety of a shortened 14-day course of aztreonam for inhalation solution (AZLI) with 28-day AZLI in paediatric pwCF. ALPINE2 (a double-blind, phase 3b study) included children aged 3 months to <18 years with CF and new-onset Pa infection. Participants were randomized to receive 75 mg AZLI three times daily for either 28 or 14 days followed by 14 days' matched placebo. The primary endpoint was rate of primary Pa eradication (no Pa detected during the 4 weeks post AZLI treatment). Non-inferiority was achieved if the lower 95% CI bound of the treatment difference between the two arms was above -20%. Secondary endpoints included assessments of Pa recurrence during 108 weeks of follow-up after primary eradication. Safety endpoints included treatment-emergent adverse events (TEAEs). In total, 149 participants were randomized (14-day AZLI, n = 74; 28-day AZLI, n = 75) and 142 (95.3%) completed treatment. Median age: 6.0 years (range: 0.3-17.0). Baseline characteristics were similar between treatment arms. Primary Pa eradication rates: 14-day AZLI, 55.9%; 28-day AZLI, 63.4%; treatment difference (CI), -8.0% (-24.6, 8.6%). Pa recurrence rates at follow-up end: 14-day AZLI, 54.1% (n = 20/37); 28-day AZLI, 41.9% (n = 18/43). TEAEs were similar between treatment arms. No new safety signals were observed. Non-inferiority of 14-day AZLI versus 28-day AZLI was not demonstrated. Both courses were well tolerated, further supporting AZLI short-term safety in paediatric and adolescent pwCF. GOV: NCT03219164. [Abstract copyright: Copyright © 2023. Published by Elsevier B.V.