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This article is a content analysis of peer-reviewed research publications from the years 2001 to 2022 to find the extent to which frequent relocation may affect the academic performance of military-connected students. There are many articles with a focus on civilian students that experience frequent residential and school mobility. However, to what extent has the extant literature focused on the military-connected student that also experiences frequent residential and school mobility? This article pays special attention to the current literature surrounding elementary-aged military-connected students. This article also examines areas of future research surrounding this group of students.

Abstract Background Expiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI). Methods A retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance. Results The mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment. Conclusions COPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.

Background: Inducible laryngeal obstruction causes narrowing of the laryngeal aperture in response to external triggers. Outcomes are measured in inducible laryngeal obstruction to monitor changes in health status over time. Methods: This study is a scoping review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The review will be guided by the following research question: 'What health outcomes are measured in studies including people with inducible laryngeal obstruction?' The research question was validated using the Population-Concept-Context framework according to the methodology for Joanna Briggs Institution Scoping Reviews. Relevant peer-reviewed studies and grey literature conducted over the last 40 years will be identified from electronic databases including AMED, CINAHL, Embase, EMCARE, MEDLINE, OVID, PubMed and PsycINFO. The search strings 'inducible laryngeal obstruction', 'ILO', 'vocal cord dysfunction', 'VCD', 'paradoxical vocal fold motion', 'PVFM', 'outcome', 'measure', 'measurement instrument', 'assessment', 'scale', 'questionnaire' will be combined using Boolean logic. An independent reviewer will conduct title screening; two independent reviewers will conduct abstract and full article screening, followed by data extraction by two reviewers. Analyses will be conducted appropriate to the findings. Discussion: The review will document evidence of health outcomes measured in inducible laryngeal obstruction, identifying measurement characteristics and potential utility. Collating studies may identify gaps in coverage, the need for novel tools, and for standardisation for clinical and research purposes.

Summary: Background: Considerable variability exists between asthma diagnostic guidelines. We tested the performance characteristics of the European Respiratory Society (ERS), the National Institute for Health and Care Excellence (NICE) and the Global Initiative for Asthma (GINA) guidelines for the diagnosis of asthma in adults. Methods: In this prospective observational study (ISRCTN—11676160, May 2019–June 2022), participants referred from primary care with clinician-suspected asthma underwent comprehensive investigation including: spirometry, bronchodilator reversibility, fractional exhaled nitric oxide, peak expiratory flow variability, bronchial challenge testing with methacholine and mannitol, and responsiveness to inhaled corticosteroid therapy. Results were reviewed by a panel of asthma specialists to determine asthma diagnosis (reference standard) and compared to each diagnostic test and the ERS, NICE and GINA diagnostic algorithms (index tests). The sensitivity, specificity, positive predictive and negative predictive values were calculated. Findings: One hundred and forty adults were enrolled and 118 given a definitive diagnostic outcome [75 female; mean (SD) age 36 (12) years; 70 (59%) with asthma] and included in the analysis. Sensitivity of individual tests was poor (15–62%), but they provided good specificity at the most stringent thresholds (range: 88–100%). The sensitivity/specificity of ERS, NICE and GINA was 81/85%, 41/100% and 47/100%, respectively. Concordance between guidelines was only moderate (Cohen’s Kappa 0.45–0.51). Interpretation: Current guidelines for the diagnosis of asthma in adults provide either excellent specificity but low sensitivity (GINA and NICE) or only reasonable sensitivity and specificity (ERS). All guidelines therefore have limitations with regards to their clinical application; new guidelines are needed but should be tested prospectively before roll out. Funding: This work was supported by the Manchester NIHR Biomedical Research Centre (BRC) (grant no. BRC-1215-20007, and NIHR203308), Asthma UK/Innovate (grant no. AUK-PG-2018-406), GSK ID 212474 and North West Lung Centre Charity.

The motivation of our study is to provide forecasters and users complementary guidance and tools to identify and predict atmospheric conditions that could lead to life-threatening flash floods. Using hourly and sub-hourly rainfall datasets, proximity radiosondes, ERA5 reanalysis of extreme rainfall events in the UK during 2000–2020, and case studies in 2021, we observe a three-layered atmospheric structure, consisting of Moist Absolute Unstable Layers (MAULs) embedded in a conditional unstable layer sandwiched between a stable upper layer and a near-stable low layer. Based on our analysis, we propose a conceptual model to describe the atmospheric properties of a ‘rainfall extreme’ environment, with a particular focus on the thermodynamics associated with sub-hourly rainfall production processes. We then set this model within a wider framework to describe the precursor synoptic and mesoscale environments necessary for sub-hourly rainfall extremes in the mid-latitudes. We show that evolution of the Omega block and Rex Vortex couplet provides the optimal environmental conditions for sub-hourly rainfall extremes. These results provide the potential to develop a ‘4-stage’ warning system to assist in the identification and forecasting of life threatening short-duration extreme rainfall intensities and flash floods.

Abstract Extremely rapid rates of rise in level and discharge in a subset of flash floods (‘abrupt wave front floods’, AWF) are separate hazards from peak level. Such flood events are investigated for Pennine catchments in northern England using both gauged and historical information. Gauged level and flow digital records at 15‐min intervals provide recent data. Historical information for 122 AWF events is extracted from a chronology of flash floods for Britain. Historical AWF events are mapped and found to occur on every major Pennine catchment; catchment descriptors are derived as a basis for assessing catchment vulnerability. We discuss the disputed origin of AWF. Using gauged data, we contrast the rising limb of AWF and ‘normal’ floods. We investigate time series of historical AWF, noting a puzzling peak in the late 19th century. Current rainfall and river monitoring does not provide a reliable basis for understanding AWF processes or for operational response and we suggest improvements. Similarly, current models for design flood estimation and forecasting do not generate the observed rapid increase in level in AWF floods.

In response to flood risk, design flood estimation is a cornerstone of planning, infrastructure design, setting of insurance premiums, and emergency response planning. Under stationary assumptions, flood guidance and the methods used in design flood estimation are firmly established in practice and mature in their theoretical foundations, but under climate change, guidance is still in its infancy. Human-caused climate change is influencing factors that contribute to flood risk such as rainfall extremes and soil moisture, and there is a need for updated flood guidance. However, a barrier to updating flood guidance is the translation of the science into practical application. For example, most science pertaining to historical changes to flood risk focuses on examining trends in annual maximum flood events or the application of non-stationary flood frequency analysis. Although this science is valuable, in practice, design flood estimation focuses on exceedance probabilities much rarer than annual maximum events, such as the 1 % annual exceedance probability event or even rarer, using rainfall-based procedures, at locations where there are few to no observations of streamflow. Here, we perform a systematic review to summarize the state-of-the-art understanding of the impact of climate change on design flood estimation in the Australian context, while also drawing on international literature. In addition, a meta-analysis, whereby results from multiple studies are combined, is conducted for extreme rainfall to provide quantitative estimates of possible future changes. This information is described in the context of contemporary design flood estimation practice to facilitate the inclusion of climate science into design flood estimation practice.

The co-occurrence of wind and rainfall extremes can yield larger impacts than when either hazard occurs in isolation. This study assesses compound extremes produced by Extra-tropical cyclones (ETCs) during winter from two perspectives. Firstly, we assess ETCs with extreme footprints of wind and rainfall; footprint severity is measured using the wind severity index (WSI) and rain severity index (RSI) which account for the intensity, duration, and area of either hazard. Secondly, we assess local co-occurrences of 6-hourly wind and rainfall extremes within ETCs. We quantify the likelihood of compound extremes in these two perspectives and characterise a number of their drivers (jet stream, cyclone tracks, and fronts) in control (1981–2000) and future (2060–2081, RCP8.5) climate simulations from a 12-member ensemble of local convection-permitting 2.2 km climate projections over the UK and Ireland. Simulations indicate an increased probability of ETCs producing extremely severe WSI and RSI in the same storm in the future, occurring 3.6 times more frequently (every 5 years compared to every 18 years in the control). This frequency increase is mainly driven by increased rainfall intensities, pointing to a predominantly thermodynamic driver. However, future winds also increase alongside a strengthened jet stream, while a southward displaced jet and cyclone track in these events leads to a dynamically-enhanced increase in temperature. This intensifies rainfall in line with Clausius-Clapeyron, and potentially wind speeds due to additional latent heat energy. Future simulations also indicate an increase in the land area experiencing locally co-occurring wind and rainfall extremes; largely explained by increased rainfall within warm and cold fronts, although the relative increase is highest near cold fronts suggesting increased convective activity. These locally co-occurring extremes are more likely in storms with severe WSI and RSI, but not exclusively so as local co-occurrence requires the coincidence of separate drivers within ETCs. Overall, our results reveal many contributing factors to compound wind and rainfall extremes and their future changes. Further work is needed to understand the uncertainty in the future response by sampling additional climate models.

Abstract Protein solubility and stability depend on the co-solutes present. There is little theoretical basis for selection of suitable co-solutes. Some guidance is provided by the Hofmeister series, an empirical ordering of anions according to their effect on solubility and stability; and by osmolytes, which are small organic molecules produced by cells to allow them to function in stressful environments. Here, NMR titrations of the protein barnase with Hofmeister anions and osmolytes are used to measure and locate binding, and thus to separate binding and bulk solvent effects. We describe a rationalisation of Hofmeister (and inverse Hofmeister) effects, which is similar to the traditional chaotrope/kosmotrope idea but based on solvent fluctuation rather than water withdrawal, and characterise how co-solutes affect protein stability and solubility, based on solvent fluctuations. This provides a coherent explanation for solute effects, and points towards a more rational basis for choice of excipients.

Abstract An inverse association between cancer and Alzheimer’s disease (AD) has been demonstrated; however, the association between cancer and mild cognitive impairment (MCI), and the association between cancer and cognitive decline are yet to be clarified. The AIBL dataset was used to address these knowledge gaps. The crude and adjusted odds ratios for MCI/AD and cognitive decline were compared between participants with/without cancer (referred to as C+ and C− participants). A 37% reduction in odds for AD was observed in C+ participants compared to C− participants after adjusting for all confounders. The overall risk for MCI and AD in C+ participants was reduced by 27% and 31%, respectively. The odds of cognitive decline from MCI to AD was reduced by 59% in C+ participants after adjusting for all confounders. The risk of cognitive decline from MCI to AD was halved in C+ participants. The estimated mean change in Clinical Dementia Rating-Sum of boxes (CDR-SOB) score per year was 0.23 units/year higher in C− participants than in C+ participants. Overall, an inverse association between cancer and MCI/AD was observed in AIBL, which is in line with previous reports. Importantly, an inverse association between cancer and cognitive decline has also been identified.

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of naringenin [FL‐no: 16.132] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. No other substances with sufficient structural similarity have been identified in existing FGEs that could be used to support a read‐across approach. The information provided on the manufacturing process, the composition and the stability of [FL‐no: 16.132] was considered sufficient. From studies carried out with naringenin, the Panel concluded that there is no concern with respect to genotoxicity. The use of naringenin as a flavouring substance at added portions exposure technique (APET) exposure levels is unlikely to pose a risk for drug interaction. For the toxicological evaluation of naringenin, the Panel requested an extended one‐generation toxicity study on naringenin, in line with the requirements of the Procedure and to investigate the consequence of a possible endocrine‐disrupting activity. The Panel considered that changes in thymus weight, litter size, post‐implantation loss and a consistent reduced pup weight in the high‐dose F2 generation could not be dismissed and selected therefore, the mid‐dose of 1320 mg/kg body weight (bw) per day for the parental males as the no observed adverse effect level (NOAEL) of the study. The exposure estimates for [FL‐no: 16.132] (31,500 and 50,000 μg/person per day for children and adults, respectively) were above the threshold of toxicological of concern (TTC) for its structural class (III). Using the NOAEL of 1320 mg/kg bw per day at step A4 of the procedure, margins of exposure (MoE) of 1590 and 630 could be calculated for adults and children, respectively. Based on the calculated MoEs, the Panel concluded that the use of naringenin as a flavouring substance does not raise a safety concern.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 2‐methyl‐1‐(2‐(5‐(p‐tolyl)‐1H‐imidazol‐2‐yl)piperidin‐1‐yl)butan‐1‐one [FL‐no: 16.134] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and is chemically synthesised. In food, it is intended to be used as a flavouring substance only in chewing gum. The chronic dietary exposure to [FL‐no: 16.134] was estimated to be 45 μg/person per day for a 60‐kg adult and 28.4 μg/person per day for a 15‐kg 3‐year‐old child. [FL‐no: 16.134] did not show genotoxicity in a bacterial reverse mutation test and an in vitro mammalian cell micronucleus assay. Based on the submitted toxicokinetic and metabolism data, it can be predicted that the flavouring substance is metabolised to innocuous products only. The Panel derived a lower confidence limit of the benchmark dose (BMDL) of 0.71 mg/kg bw per day for a 20% increase in the relative thyroid (including parathyroid) weight observed in a 90‐day toxicity study in rats. Based on this BMDL, adequate margins of exposure of 887 and 374 could be calculated for adults and children, respectively. The Panel concluded that there is no safety concern for [FL‐no: 16.134], when used as a flavouring substance at the estimated level of dietary exposure, based on the intended use and use levels as specified in Appendix B. The Panel further concluded that the combined exposure to [FL‐no: 16.134] from its use as a food flavouring substance and from its presence in toothpaste and mouthwash is also not of safety concern.

Abstract The Flood Studies Report (FSR) summer and winter design profiles are a key component of rainfall design guidance in the United Kingdom (UK). We have examined the rainfall profiles of over 70,000 extreme rainfall events with the original FSR profile methodology. This analysis reveals that rainfall profiles change with rainstorm duration but not season, contradicting one of the key assumptions in current UK rainfall design guidance. By using a method that does not artificially generate symmetrical and centred profiles we show that profile shapes are highly variable and strongly related to event duration and magnitude. Short events tend towards front‐loaded profiles, while heavy long‐duration events tend towards centred profile shapes. Finally, manual, automatic and mixed methods of deriving new design profiles for use in the UK were trialled, with consistent results. These could be used to derive new design profiles to supersede the FSR profiles. Notably, peak intensities in observed profiles and trialled summary profiles often exceeded those found in both FSR profiles. We conclude that current design profile guidance for the UK fails to account for the observed variability in event profile shapes and peak intensities and may lead to significant under‐ or over‐design of flood risk management solutions.

The absence of an accessible and quality-assured national flow dataset is a limiting factor in sub-daily hydrological modelling in Great Britain. The recent development of measuring authority APIs and projects such as the Floods and Droughts Research Infrastructure (FDRI) programme aim to facilitate access to such data. Basic quality-control (QC) of 15-minute data is performed by the data collection authorities and the National River Flow Archive (NRFA). Still, there is a need for a comprehensible and verifiable quality control methodology. This paper presents an initial assessment of the available data and examines what needs to be done for applicability of the data at national scale. The 15-minute flow series has many inconsistencies, and there are also inconsistencies with the NRFA Annual Maximum values. When producing a QCed dataset, decisions regarding the retention of data values need to be taken and recorded. Furthermore, QC should remove and rectify erroneous values, such as negative and above world record flows; and an assessment of homogeneity and truncated values in the stations could be beneficial to flag suspect data. The complex chain for production and changeability of flow and level data makes data curation and governance imperative to assure the longevity of the dataset. HIGHLIGHTS Sub-daily flow and level datasets are a step towards cutting-edge hydrological modelling in the UK.; Currently available data have no consistent quality-control checks at a national level.; Currently available data does not have traceable data versions.; There are a lot of inconsistencies in the available dataset.; A framework aiming to tackle these problems and produce a national product is presented.;

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and represents a significant global health burden with rising incidence rates, despite a more thorough understanding of the etiology and biology of HCC, as well as advancements in diagnosis and treatment modalities. According to emerging evidence, imaging features related to tumor aggressiveness can offer relevant prognostic information, hence validation of imaging prognostic features may allow for better noninvasive outcomes prediction and inform the selection of tailored therapies, ultimately improving survival outcomes for patients with HCC.

Abstract The Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/c charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1 $$\pm 0.6$$ ± 0.6 % and 84.1 $$\pm 0.6$$ ± 0.6 %, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation.

Abstract Precipitation indices based on daily gauge observations are well established, openly available and widely used to detect and understand climate change. However, in many areas of climate science and risk management, it has become increasingly important to understand precipitation characteristics, variability and extremes at shorter (sub-daily) durations. Yet, no unified dataset of sub-daily indices has previously been available, due in large part to the lesser availability of suitable observations. Following extensive efforts in data collection and quality control, this study presents a new global dataset of sub-daily precipitation indices calculated from a unique database of 18,591 gauge time series. Developed together with prospective users, the indices describe sub-daily precipitation variability and extremes in terms of intensity, duration and frequency properties. The indices are published for each gauge where possible, alongside a gridded data product based on all gauges. The dataset will be useful in many fields concerned with variability and extremes in the climate system, as well as in climate model evaluation and management of floods and other risks.

Abstract This opinion addresses the re‐evaluation of erythritol (E 968) as food additive and an application for its exemption from the laxative warning label requirement as established under Regulation (EU) No 1169/2011. Erythritol is a polyol obtained by fermentation with Moniliella pollinis BC or Moniliella megachiliensis KW3‐6, followed by purifications and drying. Erythritol is readily and dose‐dependently absorbed in humans and can be metabolised to erythronate to a small extent. Erythritol is then excreted unchanged in the urine. It does not raise concerns regarding genotoxicity. The dataset evaluated consisted of human interventional studies. The Panel considered that erythritol has the potential to cause diarrhoea in humans, which was considered adverse because its potential association with electrolyte and water imbalance. The lower bound of the range of no observed adverse effect levels (NOAELs) for diarrhoea of 0.5 g/kg body weight (bw) was identified as reference point. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) at the level of the reference point. An ADI of 0.5 g/kg bw per day was considered by the Panel to be protective for the immediate laxative effect as well as potential chronic effects, secondary to diarrhoea. The highest mean and 95th percentile chronic exposure was in children (742 mg/kg bw per day) and adolescents (1532 mg/kg bw per day). Acute exposure was maximally 3531 mg/kg bw per meal for children at the 99th percentile. Overall, the Panel considered both dietary exposure assessments an overestimation. The Panel concluded that the exposure estimates for both acute and chronic dietary exposure to erythritol (E 968) were above the ADI, indicating that individuals with high intake may be at risk of experiencing adverse effects after single and repeated exposure. Concerning the new application, the Panel concluded that the available data do not support the proposal for exemption.

This paper demonstrates the potential for crowdsourced rainfall data to infill gaps in the official rain gauge network and to provide new datasets for use in research. We use data from the Met Office Weather Observation Website (WOW) over 10 years (2011–2020) to generate two open-source datasets for Britain; multi-parameter raw data in an easy-to-use format; and an hourly rainfall dataset. We have compiled and prepared the data and detail here station selection, rain depth calculation, and data resampling to hourly intervals to create a consistent dataset for further processing (including statistical quality control) and application. Mapping the new rainfall dataset establishes that WOW observations fill spatial gaps in the official ground-based rain gauge network over Britain, particularly in urban areas. This could be particularly useful for post-event analysis of rainfall that results in pluvial flash flooding. Here, we focus on Britain but due to agreements with meteorological services in Belgium, the Netherlands, Australia, New Zealand, Sweden, and the Republic of Ireland, plus many citizen scientists globally opting to share data via WOW, there is potential for the development of similar datasets using these methods around the world. HIGHLIGHTS Processing of British citizen science crowdsourced data from the Met Office WOW database from 2011 to the end of 2020.; Distribution of rainfall data from ground-based rain gauges in Britain.; The potential of citizen science weather data.; Dataset access.;

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product SmokEz Enviro‐23 (SF‐006), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. SmokEz Enviro‐23 is obtained by pyrolysis of oak, maple, hickory, ash, birch, beech and cherry woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.01 to 3.2 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 9.5 mg/kg bw per day at the 95th percentile. The Panel concluded that four components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product SmoKEz C‐10 (SF‐005), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. SmoKEz C‐10 is obtained by pyrolysis of maple, oak, hickory, ash, birch, beech and cherry woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.01 to 5.1 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 18.1 mg/kg bw per day at the 95th percentile. The Panel concluded that five components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Smoke Concentrate 809045 (SF‐003), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Product Smoke Concentrate 809045 is obtained by pyrolysis of beech wood. The Panel concluded that the compositional data provided on the Primary Product are adequate. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.1 to 1.5 mg/kg body weight (bw) per day at the mean and from 0.2 to 5.2 mg/kg bw per day at the 95th percentile. The Panel concluded that eleven components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product proFagus Smoke R714 (SF‐001), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. ProFagus Smoke R714 is obtained by pyrolysis of beech and oak woods as main source materials. Based on the compositional data, the Panel noted that the identified and quantified proportion of the solvent‐free fraction amounts to 39 weight (wt)%, thus the applied method does not meet the legal quality criterion that at least 50% of the solvent‐free fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.7 to 10.9 mg/kg body weight (bw) per day at the mean and from 2.2 to 42.5 mg/kg bw per day at the 95th percentile. The Panel concluded that three components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for this component are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Fumokomp (SF‐009), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003 (in the renewal application the Primary Product is reported as ‘Fumokomp Conc.’). This opinion refers to an assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Fumokomp Conc. is produced by pyrolysis of beech and hornbeam woods. Gas chromatography–mass spectrometry (GC–MS) was applied for both identification and quantification of the volatile constituents of the Primary Product. Given the limitations of the method, the Panel cannot judge with confidence whether the applied method meets the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. Moreover, the Panel concluded that the absence of furan‐2(5H)‐one from the Primary Product was not convincingly demonstrated. At the maximum proposed use levels, dietary exposure estimates calculated with FAIM ranged from 0.04 to 0.9 mg/kg body weight (bw) per day at the mean and from 0.1 to 1.5 mg/kg bw per day at the 95th percentile. The information available on the 32 identified components of the Primary Product, although limited, did not indicate a concern for genotoxicity for any of these substances. However, whole mixture testing in an in vitro mouse lymphoma assay gave positive results which would require an adequate in vivo follow‐up study. In addition, the potential for aneugenicity of the Primary Product has not been adequately investigated. Accordingly, the potential safety concern for genotoxicity of the Primary Product cannot be ruled out.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Zesti Smoke Code 10 (SF‐002), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Zesti Smoke Code 10 is obtained by pyrolysis of hickory and oak woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.02 to 4.6 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 13.0 mg/kg bw per day at the 95th percentile. The Panel concluded that four components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Scansmoke SEF7525 (SF‐004), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Scansmoke SEF7525 is obtained from a tar produced from a mixture of red oak, white oak, maple, beech and hickory. Based on the compositional data, the Panel noted that the identified and quantified proportion of the solvent‐free fraction amounts to 32.6 weight (wt)%, thus the applied method does not meet the legal quality criterion that at least 50% of the solvent‐free fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with Food Additive Intake Model (FAIM) ranged from 0.6 to 3.8 mg/kg body weight (bw) per day at the mean and from 1.1 to 10.1 mg/kg bw per day at the 95th percentile. Based on the available information on genotoxicity on 44 identified components, the Panel concluded that two substances in the Primary Product, styrene and benzofuran, raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. Considering that the exposure estimates for styrene and benzofuran are above the threshold of toxicological concern (TTC) value of 0.0025 kg/kg bw per day for DNA‐reactive mutagens and/or carcinogens and since further data are needed to clarify their potential genotoxicity, the Panel concluded that the potential safety concern for genotoxicity of the Primary Product cannot be ruled out.

Rationale Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were

IMPORTANCE:. Most studies on acute respiratory distress syndrome (ARDS) group patients by severity based on their initial degree of hypoxemia. However, this grouping has limitations, including inconsistent hypoxemia trajectories and outcomes. OBJECTIVES:. This study explores the benefits of grouping patients by resolver status based on their hypoxemia progression over the first 7 days. DESIGN, SETTING, AND PARTICIPANTS:. This is an observational study from a large single-center database. Medical Information Mart for Intensive Care (MIMIC)-IV and MIMIC Chest X-ray JPEG databases were used. Mechanically ventilated patients that met the Berlin ARDS criteria were included. MAIN OUTCOMES AND MEASURES:. The primary outcome was the proportion of hypoxemia resolvers vs. nonresolvers in non-COVID-19 ARDS patients. Nonresolvers were defined as those whose hypoxemia worsened or remained moderate or severe over the first 7 days. Secondary outcomes included baseline admission characteristics, initial blood gases and ventilation settings, length of invasive mechanical ventilation, length of ICU stay, and ICU survival rates across resolver groups. RESULTS:. A total of 894 ICU admissions were included in the study. Of these, 33.9% were hypoxemia nonresolvers. The resolver groups showed no significant difference in age, body mass index, comorbidities, or Charlson score. There was no significant difference in the percentage of those with initial severe hypoxemia between the two groups (8.1% vs. 9.2%; p = 0.126). The initial Pao2/Fio2 ratio did not significantly increase the odds ratio (OR) of being a nonresolver (OR, 0.84; 95% CI, 0.65–1.10). Nonresolver mortality was 61.4%, comparable to the survival rates seen in nonresolvers in a previous large COVID-19 ARDS study. CONCLUSIONS AND RELEVANCE:. Our study shows that resolver status is a valuable grouping in ARDS. It has significant advantages over grouping by initial degree of hypoxemia, including better mapping of trajectory and comparable outcomes across other studies. While it may offer insights into disease-specific associations, future studies should include resolver status analysis for more definitive conclusions.

Abstract Understanding climate change impacts on Tropical Storm (TS) activity is crucial for effective adaptation planning and risk assessment, particularly in densely populated low‐lying delta rivers basins like the Ganges and Mekong. The change to TS characteristics with warming is uncertain due to limitations in global climate model resolution and process‐representation and storm tracking algorithms (trackers). Here, we used 13 HighResMIP models and two trackers to estimate the uncertainty in projections of TS characteristics. We found different trackers producing qualitatively similar but quantitatively different results. Our results show a decline (median ∼52%) in the frequency of TS but increase in the strongest TS and Available Cyclone Energy (ACE) of TS over both basins. The higher‐resolution models extract TS with much higher intensity and ACE values compared to the lower‐resolution models. These results have implications for adaptation planning and risk assessment for TS and suggest the need for further high‐resolution modeling studies.

We provide an overview of the assessment and management of inducible laryngeal obstruction and breathing pattern disorder. We highlight the multidisciplinary team members involved and their essential roles within a complex breathlessness service. We discuss treatments initiated by physiotherapy and speech and language therapy, the importance of joint working, and discuss the high incidence of comorbidities and the association with other respiratory disorders. Educational aims Inducible laryngeal obstruction and breathing pattern disorder are common causes of breathlessness. Inducible laryngeal obstruction is an inappropriate, transient, reversible narrowing of the laryngeal area that causes breathlessness and laryngeal symptoms. Breathing pattern disorder is an alteration in the normal biomechanical patterns of breathing that results in intermittent or chronic symptoms, which may be respiratory and/or non-respiratory. People with inducible laryngeal obstruction or breathing pattern disorder often have other comorbidities that will also need addressing. Multidisciplinary assessment and treatment is essential for comprehensive workup and holistic care. Timely assessment and diagnosis can prevent unnecessary medication use and hospital admissions and facilitate effective management of the condition using reassurance, advice, education, breathing retraining and vocal exercises.

Background: Postoperative complications are associated with reduced long-term survival. We characterise healthcare use changes after sentinel postoperative complications. Methods: We linked primary and secondary care records of patients undergoing elective surgery at four East London hospitals (2012–7) with at least 90 days follow-up. Complication codes (wound infection, urinary tract infection, pneumonia, new stroke, and new myocardial infarction) recorded within 90 days of surgery were identified from primary or secondary care. Outcomes were change in healthcare contact days in the 2 yr before and after surgery, and 2 yr mortality. We report rate ratios (RaR) with 95% confidence intervals and adjusted for baseline healthcare use and confounders using negative binomial regression. Results: We included 49 913 patients (median age 49 yr [inter-quartile range {IQR}: 34–64]), 27 958 (56.0%) were female. Amongst 3883 (7.8%) patients with complications (median age 58 [IQR: 43–72]), there were 18.4 days per year in contact with healthcare before surgery and 25.3 days after surgery (RaR: 1.38 [1.37–1.39]). Patients without complications (median age 48 [IQR: 33–63]) had 12.3 days per year in contact with healthcare before surgery and 14.0 days after surgery (RaR: 1.14 [1.14–1.15]). The adjusted incidence rate ratio of days in contact with healthcare associated with complications was 1.67 (1.49–1.87). More patients (391; 10.1%) with complications died within 2 yr than those without (1428; 3.1%). Conclusions: Patients with postoperative complications are older with greater healthcare use before surgery. However, their absolute and relative increases in healthcare use after surgery are greater than patients without complications.

We present here the first climatology of extreme sub-daily rainfall for a large part of western Europe, developed using a newly developed set of sub-daily rainfall indices, derived from a recently created global sub-daily rainfall (GSDR) dataset. The indices describe sub-daily (3-hourly) rainfall extremes in terms of their intensity, frequency and timing. Analysis of the frequency index (number of 3hr periods with >20 mm rain (R3hr20mm)) and a suite of intensity indices including the annual maxima (Rx3hr) and values of the 99.9th percentile at each gauge (R99.9p3hr) indicate a peak in the frequency and intensity of short-duration rainfall extremes in summer across most of western Europe, while areas around the north-west Mediterranean experience the highest intensities and frequencies of 3-hr rainfall in autumn. The index of contribution from 3-h annual maxima to the daily total (Rx3hrP) indicates that these events are often produced by very short-duration or very peaked storms, with a tendency towards a late afternoon or evening peak in the time of occurrence. There are also clear differences in the spatiotemporal occurrence of the sub-daily extremes when compared to extreme daily rainfall indices, which could have repercussions for flood management. Additional analysis of the sub-daily rainfall indices within the context of Köppen-Geiger climate zones indicates Mediterranean-type climate zones experience more intense and more frequent sub-daily extremes, while the intensity of rainfall within cooler climate zones is lower and the most intense events are restricted to summer. The climate zones are found to be a relatively good indicator of the extreme rainfall characteristics that can be expected in a region. Being able to compare sub-daily rainfall characteristics across a wide region in this manner greatly enhances our ability to investigate future variability and change in sub-daily extremes and will aid in high-resolution climate model validation.

Two convection-permitting climate models project similar increases in peak rainfall intensities from mesoscale convective storms across Europe by 2100, but project contrasting changes to storm frequency, size, and speed due to differences in the representation of dynamical responses to global warming.

Antimicrobial resistance is increasing in prevalence and there is a clear need for the development of rapid detection methods in clinical diagnostics. This review explores –omics studies utilising mass spectrometry to investigate the molecular phenotype associated with carbapenem resistance. Whilst the specific mechanisms of carbapenem resistance are well characterised, the resistant phenotype is poorly understood. Understanding how the acquisition of resistance affects cellular physiology and cell metabolism through molecular phenotyping is a necessary step towards detecting resistance by diagnostic means. In addition, this article examines the potential of mass spectrometry for the identification of resistance biomarkers through molecular profiling of bacteria. Developments in mass spectrometry platforms are expanding the biomarker-based diagnostic landscape. Targeted measures, such as high-resolution mass spectrometry coupled with chromatographic separation show considerable promise for the identification of molecular signatures and the development of a rapid diagnostic assay for the detection of carbapenem resistance.

A ‘roadmap’ for the future of UK flood hydrology over the next 25 years has been published, based on a wide-ranging and inclusive co-creation process involving more than 270 individuals and 50 organisations from different sectors and disciplines. This paper highlights key features of the roadmap and its development as a community-owned initiative. The roadmap's relationship with hydrological research and practice is discussed, as is its context within the wider flood risk management innovation landscape, including funding. While the paper has a focus on UK flood hydrology, reflecting the scope of the roadmap, it is also considered in the context of advances in hydrology internationally. HIGHLIGHTS A roadmap for UK flood hydrology over the next 25 years.; The roadmap has been published on behalf of the flood hydrology community.; Over 270 individuals and 50 organisations contributed to the roadmap's development.; The roadmap will inform many flood risk management activities to strengthen community, infrastructure and climate resilience.; The roadmap spans science, practice and the evolution of the professional community.;

Abstract Liquid argon time projection chamber detector technology provides high spatial and calorimetric resolutions on the charged particles traversing liquid argon. As a result, the technology has been used in a number of recent neutrino experiments, and is the technology of choice for the Deep Underground Neutrino Experiment (DUNE). In order to perform high precision measurements of neutrinos in the detector, final state particles need to be effectively identified, and their energy accurately reconstructed. This article proposes an algorithm based on a convolutional neural network to perform the classification of energy deposits and reconstructed particles as track-like or arising from electromagnetic cascades. Results from testing the algorithm on experimental data from ProtoDUNE-SP, a prototype of the DUNE far detector, are presented. The network identifies track- and shower-like particles, as well as Michel electrons, with high efficiency. The performance of the algorithm is consistent between experimental data and simulation.

Abstract Calcium carbonate (E 170) was re‐evaluated in 2011 by the former EFSA Panel on Food Additives and Nutrient sources added to Food (ANS). As a follow‐up to this assessment, the Panel on Food Additives and Flavourings (FAF) was requested to assess the safety of calcium carbonate (E 170) for its uses as a food additive in food for infants below 16 weeks of age belonging to food category 13.1.5.1 (Dietary foods for infants for special medical purposes and special formulae for infants) and as carry over in line with Annex III, Part 5 Section B to Regulation (EC) No 1333/2008. In addition, the FAF Panel was requested to address the issues already identified during the re‐evaluation of the food additive when used in food for the general population. The process involved the publication of a call for data to allow the interested business operators (IBOs) to provide the requested information to complete the risk assessment. The Panel concluded that there is no need for a numerical acceptable daily intake (ADI) for calcium carbonate and that, in principle, there are no safety concern with respect to the exposure to calcium carbonate per se at the currently reported uses and use levels in all age groups of the population, including infants below 16 weeks of age. With respect to the calcium intake resulting from the use of E 170 in food for the general population and infants

The potential compounding behaviour of heatwaves and extreme rainfall have important implications for a range of hazards, including wildfires and flooding, yet remain poorly understood. In this global study, we analyse the likelihood of extreme 1-hr rainfall immediately following a heatwave, and identify climate zones where this phenomenon is most pronounced. We find the strongest compounding heatwave-extreme rainfall relationships in central Europe and Japan, where the likelihood of extreme rainfall after a heatwave is increased by approximately four times compared to climatology. Significant compounding is found mainly in temperate or colder climates, provided these areas receive ample moisture. As both heatwaves and extreme rainfall are expected to become more frequent in the future, our results indicate that the potential impacts from compounding heatwave-extreme rainfall events might significantly increase as well.

Extratropical windstorms can lead to extreme impacts in the UK; however, future changes in windstorm frequency and intensity are uncertain due to natural variability and lack of model consensus. Further uncertainty arises due to unresolved or poorly represented processes which can reduce the validity of traditional coarse resolution climate models. This study demonstrates the added value of higher resolution simulations in their representation of extreme windstorms. It also assesses future changes in windstorms in the first ensemble of convection-permitting model (CPM, 2.2 km grid spacing) projections over the UK, released as part of the UKCP18 project, and compares these to changes in the driving 60 km global climate model (GCM) and 12 km regional climate model (RCM). The representation of wind gusts in the CPM and RCM is improved with respect to ERA-Interim reanalysis data compared to observations. Both models are largely similar except over areas with orographic influences where the CPM provides greater detail and simulates higher wind gusts. In contrast, the GCM simulates lower wind gusts and underestimates windstorm intensity; the improvements from the RCM and CPM are partially linked to better representation of cold conveyor belts and sting jets at km-scale. The CPM projects an increase in the frequency of extreme windstorms. In line with a previous study, a large contribution comes from storms that develop sting jets which now seems to be a robust response of windstorms to a warming climate. Similar projected increases are also found in the coarser resolution models, although differences in projections exist at a regional scale in the CPM compared to the RCM and GCM. Overall, higher resolution simulations improve the representation of windstorms, offering greater detail at the local scale which may provide better information for impact modelling, though large-scale projected changes in the assessed storm severity index are insensitive to the model resolutions in the simulations tested here.

Africa has the largest area of wetlands of international importance, and papyrus constitutes the most dominant species for many of these wetlands. This hydrological modelling study assesses and quantifies the impacts of these papyrus wetlands on historical baseflow and quickflow, as well as future flood and low flows in the Mpologoma catchment in Uganda. Assessment over the historic period shows that wetlands strongly attenuate quickflow while moderately enhancing baseflow. They play a moderating role in most months, except for the first dry season (June and July), due to the reversal of flows between wetlands and rivers that often occur during this period. Annual estimates show that wetlands are four times better at regulating quickflow than baseflow. Examination of changes at 2 and 4 °C global warming levels (GWLs) indicate that wetlands will play critical roles in mitigating flood risks, with a lesser role in supporting low flows. Wetlands are predicted to lower future mean flood magnitude by 5.2 and 7.8% at GWL2 and GWL4, respectively, as well as halving the average number of flood events in a year, irrespective of the warming level. This work shows that papyrus-dominated wetlands strongly influence catchment hydrology, with significant roles on quickflow, including floods, and highlights the need for their conservation and protection.