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Abstract Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition. This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines. Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient’s journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working. Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.

In her late 50 s, a woman with a medical history of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) experienced a relapse of nasal polyps, significantly impacting her breathing and sense of smell. She underwent a multifaceted treatment approach, including oral corticosteroids, functional endoscopic sinus surgery, and omalizumab injections. Digital high-speed videomicroscopy (DHSV) revealed only partial improvement in ciliary beat pattern and ciliary beat frequency with oral corticosteroid treatment, while significant improvement in these ciliary parameters was observed with omalizumab injections. Furthermore, administration of omalizumab resulted in a decrease in her SNOT-22 (Sinonasal Outcome Test 22) score. Notably, this case report represents the first study investigating ciliary function using DHSV in a patient treated with omalizumab.

Background Randomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12 months. Methods Patients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6 months and then every year. Results We found significant reductions in exacerbations (by 92%, p

Field boundaries are at the core of many agricultural applications and are a key enabler for the operational monitoring of agricultural production to support food security. Recent scientific progress in deep learning methods has highlighted the capacity to extract field boundaries from satellite and aerial images with a clear improvement from object-based image analysis (e.g. multiresolution segmentation) or conventional filters (e.g. Sobel filters). However, these methods need labels to be trained on. So far, no standard data set exists to easily and robustly benchmark models and progress the state of the art. The absence of such benchmark data further impedes proper comparison against existing methods. Besides, there is no consensus on which evaluation metrics should be reported (both at the pixel and field levels). As a result, it is currently impossible to compare and benchmark new and existing methods. To fill these gaps, we introduce AI4Boundaries, a data set of images and labels readily usable to train and compare models on field boundary detection. AI4Boundaries includes two specific data sets: (i) a 10 m Sentinel-2 monthly composites for large-scale analyses in retrospect and (ii) a 1 m orthophoto data set for regional-scale analyses, such as the automatic extraction of Geospatial Aid Application (GSAA). All labels have been sourced from GSAA data that have been made openly available (Austria, Catalonia, France, Luxembourg, the Netherlands, Slovenia, and Sweden) for 2019, representing 14.8 M parcels covering 376 K km2. Data were selected following a stratified random sampling drawn based on two landscape fragmentation metrics, the perimeter/area ratio and the area covered by parcels, thus considering the diversity of the agricultural landscapes. The resulting “AI4Boundaries” dataset consists of 7831 samples of 256 by 256 pixels for the 10 m Sentinel-2 dataset and of 512 by 512 pixels for the 1 m aerial orthophoto. Both datasets are provided with the corresponding vector ground-truth parcel delineation (2.5 M parcels covering 47 105 km2), and with a raster version already pre-processed and ready to use. Besides providing this open dataset to foster computer vision developments of parcel delineation methods, we discuss the perspectives and limitations of the dataset for various types of applications in the agriculture domain and consider possible further improvements. The data are available on the JRC Open Data Catalogue: http://data.europa.eu/89h/0e79ce5d-e4c8-4721-8773-59a4acf2c9c9 (European Commission, Joint Research Centre, 2022).

Immune checkpoint inhibitor (ICI) therapy has proven revolutionary in the treatment of some cancers. However, ovarian cancer remains unresponsive to current leading ICIs, such as anti-PD1 or anti-PD-L1. In this article, we explored the potential of an upcoming checkpoint molecule, T-cell immunoglobulin and mucin domain 3 (TIM3), for the treatment of ovarian cancer using a syngeneic orthotopic mouse model (ID8-fLuc). Besides therapeutic efficacy, we focused on exploring immune changes in tumor tissue and peritoneal fluid. Our results showed no improvement in survival in ovarian cancer-bearing mice after anti-TIM3 treatment when used as monotherapy nor when combined with anti-PD1 or standard-of-care chemotherapy (carboplatin/paclitaxel). This was reflected in the unaltered immune infiltration in treated mice compared to control mice. Altering the order of drug administration within the combination treatment altered the survival results, but did not result in a survival benefit over chemotherapy alone. These findings highlight the need for further preclinical studies to find beneficial treatment schemes and combination therapies for ovarian cancer.

Background: Impulsivity is a multifaceted construct that plays a prominent role in substance use disorder (SUD). The UPPS-P model distinguishes five impulsivity components (positive urgency, negative urgency, lack of perseverance, lack of premeditation, and sensation seeking). This study aimed to explore the structure of the UPPS-P in patients hospitalized for SUDs and to investigate the relationship between the dimensions of impulsivity and clinical variables. Method: Inpatients of a residential detoxification service ( n = 125) were recruited. A confirmatory factor analysis was performed, and associations were assessed between the components of impulsivity and clinical indexes. Results: The factor analysis supported a model of impulsivity with five interrelated latent variables. Good internal consistency was found. External validity was supported by relationships with psychological difficulties. Multiple correlations (Kendall) suggested that, except for its sensation-seeking component, impulsivity is a significant risk factor for both the severity of addictive problems and their comorbidities. Conclusion: This study provides further evidence in favor of the 5-dimensional model of impulsivity. It highlights impulsivity as a transdiagnostic risk factor that should be considered in the management of SUD.

Background Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD. Methods We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression. Results 12 centres contributed 384 participants; median age was 16 years (IQR 9–22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23–45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older. Conclusions Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines.

Background and study aims Pancreatoscopy-guided electrohydraulic lithotripsy (EHL) has proven to be an effective first-line therapy in symptomatic chronic pancreatitis (CP) patients with obstructing pancreatic duct (PD) stones 1. However, long-term outcomes of endoscopic EHL remain unknown. The aim of the present study was to evaluate the long-term treatment effects of EHL as first-line therapy and to compare with those obtained in a historical cohort of patients who underwent extracorporeal shockwave lithotripsy (ESWL) as primary treatment. Patients and methods An observational retrospective single-center long-term follow-up study was performed including 19 consecutive patients who previously underwent endoscopic EHL compared to 18 patients who underwent ESWL followed by endoscopic retrograde pancreatography (ERP). The primary endpoint was long-term treatment success after EHL or ESWL defined as no recurrence of symptomatic intraductal stones confirmed on imaging. Secondary endpoints for the EHL-population included long-term clinical success (i. e., a similar or lower Izbicki Pain Score or reduction in opiate usage as compared to 6-month follow-up), quality of life (QoL), pancreatic function and hospital re-admission rate. Results In the EHL group, 37 % of the patients developed recurrent symptomatic PD stones versus 61 % in the ESWL group after a median follow-up of 35.0 and 76.5 months. Of the patients with recurrence, 71 % versus 100 % underwent a reintervention. Median time to recurrence was 12.0 versus 13.0 months. Clinical success sustained in 58 % of the EHL patients. QoL was not significantly different compared with 6-month follow-up and baseline. Conclusions Also at long-term follow-up, endoscopic EHL as first-line treatment is moderately effective for symptomatic CP patients with treatment success rates that seems at least equally effective as ESWL.

Primary ciliary dyskinesia is a heterogeneous, inherited motile ciliopathy in which respiratory cilia beat abnormally, and some ultrastructural ciliary defects and specific genetic mutations have been associated with particular ciliary beating alterations. Ciliary beating can be evaluated using digital high-speed videomicroscopy (DHSV). However, normal reference values, essential to assess ciliary beating in patients referred for a PCD diagnostic, vary between centres, as minor variations in protocols might influence ciliary beating. Consequently, establishment of normal values is essential for each PCD diagnostic centre. We aimed to evaluate whether delay after sampling, and temperature for conservation of respiratory ciliated samples, might modify assessments of ciliary beating. In total, 37 healthy nasal brushing samples of respiratory ciliated epithelia were collected. Video sequences were recorded at 37 °C immediately using DHSV. Then, the samples were divided and conserved at 4 °C or at room temperature (RT). Ciliated beating edges were then recorded at 37 °C, at 3 h and at 9 h post sampling. In six samples, recordings were continued up to 72 h after sampling. Ciliary beating was assessed manually by ciliary beat frequency (CBFM) and ciliary beat pattern (CBP). A semi-automatic software was used for quantitative analysis. Both CBF and CBP evaluated manually and by a semi-automated method were stable 9 h after sampling. CBFM was higher when evaluated using samples stored at RT than at 4 °C. CBP and the semi-automated evaluation of ciliary beating were not affected by storage temperature. When establishing normal references values, ciliary beating can be evaluated at 37 °C up to 9 h after nasal brushing, but the storage temperature modifies ciliary beating and needs to be controlled.

The assessment of working time recording practices and their impacts on the workers’ well-being, work-life balance and health is lacking in the scientific literature with only rare exceptions. Nevertheless, this issue is becoming increasingly important especially in Switzerland. Despite the fact that the Labour Law requires to record all working hours, some categories of workers are released from this legal obligation, in particular those who benefit from more autonomy and flexible working schedules. This paper assesses the potential risk that differentiated working time regimes can have on workers’ health. The analyses are based on a sample from eight companies that apply these legal exemptions. The main outcome is that long working hours represent the main health risk factor for workers that do not record all their working hours.

Time series of optical remote sensing data are instrumental for monitoring vegetation dynamics, but are hampered by missing or noisy observations due to varying atmospheric conditions. Reconstruction methods have been proposed, most of which focus on time series of a single vegetation index. Under the assumption that relatively high vegetation index values can be considered as trustworthy, a successful approach is to adjust the smoothed value to the upper envelope of the time series. However, this assumption does not hold for surface reflectance in general. Clouds and cloud shadows result in, respectively, high and low values in the visible and near infrared part of the electromagnetic spectrum. A novel spectral Reflectance Time Series Reconstruction (RTSR) method is proposed. Smoothed values of surface reflectance values are adjusted to approach the trustworthy observations, using a vegetation index as a proxy for reliability. The Savitzky–Golay filter was used as the smoothing algorithm here, but different filters can be used as well. The RTSR was evaluated on 100 sites in Europe, with a focus on agriculture fields. Its potential was shown using different criteria, including smoothness and the ability to retain trustworthy observations in the original time series with RMSE values in the order of 0.01 to 0.03 in terms of surface reflectance.

DPF3, along with other subunits, is a well-known component of the BAF chromatin remodeling complex, which plays a key role in regulating chromatin remodeling activity and gene expression. Here, we elucidated a non-canonical localization and role for DPF3. We showed that DPF3 dynamically localizes to the centriolar satellites in interphase and to the centrosome, spindle midzone and bridging fiber area, and midbodies during mitosis. Loss of DPF3 causes kinetochore fiber instability, unstable kinetochore-microtubule attachment and defects in chromosome alignment, resulting in altered mitotic progression, cell death and genomic instability. In addition, we also demonstrated that DPF3 localizes to centriolar satellites at the base of primary cilia and is required for ciliogenesis by regulating axoneme extension. Taken together, these findings uncover a moonlighting dual function for DPF3 during mitosis and ciliogenesis. [ABSTRACT FROM AUTHOR]

Background Genetic risk factors can provide insight into susceptibility for acute pancreatitis (AP) and disease progression towards (infected) necrotizing pancreatitis and persistent organ failure. The aim of the study was to undertake a systematic review of the genetic evidence for AP. Methods Online databases (MEDLINE, Embase, BIOSIS, Web of Science, Cochrane Library) were searched to 8 February 2018. Studies that reported on genetic associations with AP susceptibility, severity and/or complications were eligible for inclusion. Meta‐analyses were performed of variants that were reported by at least two data sources. Venice criteria and Bayesian false‐discovery probability were applied to assess credibility. Results Ninety‐six studies reporting on 181 variants in 79 genes were identified. In agreement with previous meta‐analyses, credible associations were established for SPINK1 (odds ratio (OR) 2·87, 95 per cent c.i. 1·89 to 4·34), IL1B (OR 1·23, 1·06 to 1·42) and IL6 (OR 1·64, 1·15 to 2·32) and disease risk. In addition, two novel credible single‐nucleotide polymorphisms were identified in Asian populations: ALDH2 (OR 0·48, 0·36 to 0·64) and IL18 (OR 1·47, 1·18 to 1·82). Associations of variants in TNF, GSTP1 and CXCL8 genes with disease severity were identified, but were of low credibility. Conclusion Genetic risk factors in genes related to trypsin activation and innate immunity appear to be associated with susceptibility to and severity of AP.