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Nitrogen oxides, emitted from air traffic, are of concern due to their impact on climate by changing atmospheric ozone and methane levels. Using the DLR research aircraft Falcon, total reactive nitrogen (NOy) in-flight measurements were carried out at high altitudes to characterize emissions in the fresh aircraft exhaust from the latest-generation Rolls-Royce Trent XWB-84 engine aboard the long-range Airbus A350-941 aircraft during the ECLIF3 (Emission and CLimate Impact of alternative Fuels 3) experiment. The impact of different engine thrust settings, monitored in terms of combustor inlet temperature, pressure and engine fuel flow, was tested for two different fuel types: Jet A-1 and, for the first time, a 100 % sustainable aviation fuel (SAF) under similar atmospheric conditions. In addition, a range of combustor temperatures and an additional blended SAF were tested during ground-based emission measurements. For the data measured during ECLIF3, we confirm that the NOx emission index increases with increasing combustion temperature, pressure and fuel flow. We find that as expected, the fuel type has no measurable effect on the NOx emission index. These measurements are used to compare to cruise NOx emission index estimates from three engine emission prediction methods. Our measurements thus help to understand the ground to cruise correlation of current engine emission prediction methods while serving as input for climate modelling and extending the extremely sparse data set on in-flight aircraft nitrogen oxide emissions to newer engine generations.

In order to reduce aviation's CO2 emissions and comply with current climate targets, the European Union plans a mandatory quota of 2 % sustainable aviation fuel (SAF) by 2025, rising up to ≥70 % SAF by 2050. In addition to a reduction of life cycle CO2 emissions, the use of SAF can also have a positive impact on particle emissions and contrail properties. In this study we present observations from the ECLIF3 (Emission and CLimate Impact of alternative Fuels) aircraft campaign, which investigated exhaust and contrail characteristics of an Airbus A350-941 equipped with Rolls-Royce Trent XWB-84 engines. For the first time, non-volatile and total particle emissions of 100 % HEFA-SPK (hydroprocessed esters and fatty acids–synthetic paraffinic kerosene) SAF, a blended fuel and a reference Jet A-1 fuel were measured in flight. A maximum reduction in non-volatile particle number emissions of ∼41 % compared to the reference Jet A-1 fuel was measured at low cruise engine power settings when using 100 % HEFA-SPK. The reduction decreases to ∼29 % for typical cruise engine settings and to ∼22 % at high cruise engine power settings. The size of non-volatile particles was slightly smaller for HEFA-SPK compared to Jet A-1. We show a comprehensive analysis of the hydrogen content of globally available fuels. Our results demonstrate the impact of the fuel composition in terms of its aromatic, hydrogen, and sulfur content as well as of the effect of engine power settings on particle emissions. We demonstrate that the use of HEFA-SPK can significantly reduce particle emissions and thus contrail ice particles and therefore can provide an aviation climate benefit.

Abstract Background Merkel cell carcinomas are rare, aggressive skin tumors with high metastatic potential and poor prognosis. Their treatment is classically based on surgery with adjuvant external radiotherapy for localized tumors or on immunotherapy or chemotherapy, sometimes associated with radiotherapy, for metastatic stages. Those tumors are highly radiosensitive due to their neuroendocrine and undifferentiated nature, but they usually fail to rapidly respond to treatment. Case presentation We report the case of a 65-year-old retired female patient of Caucasian (German) origin with locally advanced Merkel cell carcinoma of the buttock, with pancreatic metastases synchronous at diagnosis, treated with local radiotherapy of the right buttock without regional lymph node irradiation followed by a sequential chemotherapy; 1 year later, the patient developed an isolated pancreatic recurrence treated with exclusive radiotherapy. The patient was still alive at 13 years with complete remission. Conclusion External radiotherapy can be an effective alternative to surgery for locally advanced or even oligometastatic Merkel cell carcinomas.

Abstract Background The benefits of comprehensive geriatric assessment (CGA) are well established for hospital care but less so for primary care. Our primary objective was to assess the effect of two multifaceted interventions based on a CGA adapted for primary care on a composite criterion combining all-cause mortality, emergency department visits, unplanned hospital admissions, and institutionalisation. Methods This open-label, pragmatic, three-arm, cluster-randomised controlled trial involved 39 general practices in France. It included 634 patients aged 70 years or over with chronic health conditions and/or an unplanned hospital admission in the past 3 months, between 05/2016 and 08/2018. Interventions were in arm 1: a systematic nurse-led CGA; arm 2: a GP-led CGA, at the GP’s discretion; arm 3: standard care. The primary composite endpoint was assessed at 12 months. The secondary endpoints included: components of the composite endpoint, health-related quality of life (Duke Health Profile), functional status (Katz Activities of Daily Living Index) and medications (number) at 12 months. Pairwise comparisons between the experimental groups and the control were tested. The main analysis was performed on the intention-to-treat (ITT) population, after imputing missing information and adjusting for baseline imbalances by mixed effects regressions. Results For the primary composite outcome, no statistically significant difference was found between arm 1 and the control (adjusted odds ratio [aOR] = 0.81 [95%CI 0.54–1.21], P = 0.31), whereas arm 2 and the control differed significantly (aOR = 0.60 [0.39–0.93], P = 0.022). A statistically lower risk of unplanned hospital admission in arm 2 vs control (aOR = 0.57 [0.36–0.92], P = 0.020)) was observed, while no statistically significant differences were found for the other components and between arm 1 and the control. None of the other secondary endpoints differed between arms. Conclusions Our study led in community-dwelling older patients with chronic conditions found no significant effect of a CGA adapted for primary care on mortality, functional independence and quality of life, but suggests that a GP-led CGA may reduce the risk of unplanned hospital admission. Our study demonstrates the feasibility of incorporating CGA into clinical practice and highlights its potential benefits when applied on a case-by-case basis, guided by the GPs who develop the resulting PCP. Trial registration NCT02664454.

Abstract Background To describe French general practioners’ (GPs) adaptation strategies to ensure follow-up care of nursing home patients during the first wave of COVID-19 (May 2020) and to identify factors associated with each strategy. Methods A national cross-sectional study was conducted with online questionnaires in May 2020 among GPs practicing in France (metropolitan and overseas) and usually providing nursing home visits before pandemic. The outcome was defined as the GPs’ adaptation strategies for managing nursing home patients and was categorized into four groups: Maintenance of Nursing Home Visits NHV (reference), Stopping NHV, Numeric adaptation (teleconsultations only), Mixed adaptation (NHV and teleconsultations). The probability of adaptation strategies was analyzed by multilevel logistic models in which the GPs represented level 1 and the counties level 2. We applied three random-intercept multilevel logistic models with the county of GP’s practice as random effect. Results This analysis included 2,146 responses by GPs coming from 98 French counties. Overall, 40.4% of GPs maintained NHV, while other strategies were: Stopping visits (24.1%), Numeric adaptation (15.4%), Mixed adaptation (20.1%). Several individual (age, training GP, perceived status of being at high risk of severe COVID, compliance with temporary delegation of the patient’s management) and territorial factors (excess mortality rate due to COVID-19, GPs’ density, proportion of over-75s, presence of reinforcement measures for nursing home patients) were identified as associated with each strategy. Conclusions This study highlights a rapid adaptation of general practice to keep supporting nursing home patients. Heterogeneity of adaptation strategies could reflect both the lack of national guidelines and the heterogeneity among GPs’ usual practices. Policymakers should take actions at a territorial level (subnational) to strengthen support to nursing home patients considering adaptations to the local context of the pandemic outbreak and perspective of local actors.

Transparency in the reporting of empirical studies is foundational to a credible knowledge base. Higher levels of transparency, in addition to clarity in writing, also make research more accessible to a diverse readership. Previous research reviewed how transparently reported qualitative, interview-based, studies were in contemporary technology education research (Buckley et al. in Int J Technol Des Educ, 2021a. https://doi.org/10.1007/s10798-021-09695-1). The results illustrated that no article was fully transparent and that authors tended to be less transparent in some areas, such as the management of power imbalances and a saturation point, than in others, such as the methodology adopted and research setting. This article presents a similar study, however the focus of the investigation was on contemporary quantitative technology education research. An analysis of 46 articles revealed again that no article was fully transparent and that authors tended to be more transparent in some areas than others. Interestingly, the areas where authors or quantitative research tended to be more or less transparent were similar to the areas in which authors of qualitative research tended to be more or less transparent. These results have use in supporting researchers in the clear and transparent reporting of the empirical work and could be useful in the development of guides or support material for academic writing.

Abstract Background Fungi play a key role in several important ecological functions, ranging from organic matter decomposition to symbiotic associations with plants. Moreover, fungi naturally inhabit the human body and can be beneficial when administered as probiotics. In mycology, the internal transcribed spacer (ITS) region was adopted as the universal marker for classifying fungi. Hence, an accurate and robust method for ITS classification is not only desired for the purpose of better diversity estimation, but it can also help us gain a deeper insight into the dynamics of environmental communities and ultimately comprehend whether the abundance of certain species correlate with health and disease. Although many methods have been proposed for taxonomic classification, to the best of our knowledge, none of them fully explore the taxonomic tree hierarchy when building their models. This in turn, leads to lower generalization power and higher risk of committing classification errors. Results Here we introduce HiTaC, a robust hierarchical machine learning model for accurate ITS classification, which requires a small amount of data for training and can handle imbalanced datasets. HiTaC was thoroughly evaluated with the established TAXXI benchmark and could correctly classify fungal ITS sequences of varying lengths and a range of identity differences between the training and test data. HiTaC outperforms state-of-the-art methods when trained over noisy data, consistently achieving higher F1-score and sensitivity across different taxonomic ranks, improving sensitivity by 6.9 percentage points over top methods in the most noisy dataset available on TAXXI. Conclusions HiTaC is publicly available at the Python package index, BIOCONDA and Docker Hub. It is released under the new BSD license, allowing free use in academia and industry. Source code and documentation, which includes installation and usage instructions, are available at https://gitlab.com/dacs-hpi/hitac .

The flow of glaciers is largely controlled by changes at the ice–bed interface, where basal slip and sediment deformation drive basal glacier motion. Determining subglacial conditions and their responses to hydraulic forcing remains challenging due to the difficulty of accessing the glacier bed. Here, we monitor the interplay between surface runoff and hydro-mechanical conditions at the base of the Kongsvegen glacier in Svalbard. From July 2021 to August 2022, we measured both subglacial water pressure and till strength. Additionally, we derived median values of subglacial hydraulic gradient and radius of channelized subglacial drainage system from seismic power, recorded at the glacier surface. To characterize the variations in the subglacial conditions caused by changes in surface runoff, we investigate the variations of the following hydro-mechanical properties: measured water pressure, measured sediment ploughing forces, and derived hydraulic gradient and radius, over seasonal, multi-day, and diurnal timescales. We discuss our results in light of existing theories of subglacial hydrology and till mechanics to describe subglacial conditions. We find that during the short, low-melt-rate season in 2021, the subglacial drainage system evolved at equilibrium with runoff, increasing its capacity as the melt season progressed. In contrast, during the long and high-melt-rate season in 2022, the subglacial drainage system evolved transiently to respond to the abrupt and large water supply. We suggest that in the latter configuration, the drainage capacity of the preferential drainage axis was exceeded, promoting the expansion of hydraulically connected regions and local weakening of ice–bed coupling and, hence, enhanced sliding.

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Abstract Background Childhood cancer survivors face high risks of adverse late health effects. Long‐term follow‐up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high‐quality long‐term follow‐up care, we explored expected barriers and facilitators for establishing this follow‐up care among healthcare providers from four European clinics. Methods A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi‐structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. Results Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long‐term follow‐up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long‐term follow‐up care results to convince hospital managers. Conclusion This study identified several factors for successful implementation of long‐term follow‐up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors.

IntroductionThe Stratigraphic Pile (SP) is one of the foundation of most geological studies. It represents, in a compact and practical way, a vertical succession of depositional events over geological time. Accurate definition of the SP is crucial for geological modeling, yet challenges arise when relying on borehole data in the absence of clear biostratigraphic indicators or chronostratigraphical data.MethodsThis manuscript introduces an algorithm designed to automatically determine the SP using borehole unit sequences. The algorithm also addresses the complexities associated with incomplete sedimentological records and subjective geological interpretations. The algorithm was tested on various datasets, taking into account differences in the number of boreholes and available information.Results and DiscussionThe efficiency of the algorithm was demonstrated through real-world applications, providing a basis for a comprehensive discussion of its advantages, limitations, and potential applications. The proposed methodology assumes that each borehole contains a single occurrence of a stratigraphic unit, taking into account possible interpretation errors and inconsistencies. The algorithm is capable of: automatically determining one or an ensemble of plausible stratigraphic sequences, identifying potential misinterpreted wells, quantifying the vertical relationships of the stratigraphic units, and assisting in the data preprocessing step and in building the geologic concept of the modeling area. In particular, this ensemble of SPs and identified inconsistencies provide valuable insights into the geological history and concepts for a particular area.ConclusionThis research contributes to the refinement of geological modeling workflows and provides a valuable tool for automatic refinement of SP selection.

Geostatistical cascade modeling of Mineral Resources is challenging in vein-type gold deposits. The narrow shape and long-range features of these auriferous veins, coupled with the paucity of drill-hole data, can complicate the modeling process and make the use of two-point geostatistical algorithms impractical. Instead, multiple-point geostatistics techniques can be a suitable alternative. However, the most challenging part in implementing the MPS is to use a suitable training data set or training image (TI). In this paper, we suggest using the radial basis function algorithm to build a training image and the DeeSse algorithm, one of the multiple-point statistics (MPS) methods, to model two long-range veins in a gold deposit. It is demonstrated that DeeSse can replicate long-range vein features better than plurigaussian simulation techniques when there is a lack of conditioning data. This is shown by several validation processes, such as comparing simulation results with an interpretive geological block model and replicating geological proportions.

Abstract The 2019 German Digital Healthcare Act introduced the Digital Health Application program, known in German as ‘Digitale Gesundheitsanwendungen’ (DiGA). The program has established a pioneering model for integrating Digital Therapeutics (DTx) into a healthcare system with scalable and effective reimbursement strategies. To date, the continuous upward trend enabled by this framework has resulted in more than 374,000 DiGA prescriptions, increasingly cementing its role in the German healthcare system. This perspective provides a synthesis of the DiGA program’s evolution since its inception three years ago, highlighting trends regarding prescriptions and pricing as well as criticisms and identified shortcomings. It further discusses forthcoming legislative amendments, including the anticipated integration of higher-risk medical devices, which have the potential to significantly transform the program. Despite encountering challenges related to effectiveness, evidence requirements, and integration within the healthcare system, the DiGA program continues to evolve and serves as a seminal example for the integration of DTx, offering valuable insights for healthcare systems globally.

Abstract Background Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures. Preterm infants and neonatal mice were stratified into four groups: antibiotics only, probiotics only, antibiotics followed by probiotics, and none of these interventions. Stool samples from both preterm infants and neonatal mice were collected at varying time points and analyzed by 16 S rRNA amplicon sequencing, ITS amplicon sequencing and whole genome shotgun sequencing. Results The human infant microbiomes showed an unexpectedly high degree of heterogeneity. Little impact from medical exposure (antibiotics/probiotics) was observed on the strain patterns, however, Bifidobacterium bifidum was found more abundant after exposure to probiotics, regardless of prior antibiotic administration. Twenty-seven antibiotic resistant genes were identified in the resistome. High intra-variability was evident within the different treatment groups. Lastly, we found significant effects of antibiotics and probiotics on the mycobiome but not on the microbiome and resistome of preterm infants. Conclusions Although our analyses showed transient effects, these results provide positive motivation to continue the research on the effects of medical interventions on the microbiome, resistome and mycobiome of preterm infants.

Abstract Introduction Even though the local tolerance of prostaglandin (PG) analogues has improved drastically since the introduction of preservative-free (PF) eye drops, prescription patterns still vary widely among practitioners and between countries and could have an impact on the ocular surface of treated patients and, in consequence, their adherence. The aim of this study is to explore the prescribing patterns of PG analogues monotherapy in France and to evaluate their impact on ocular surface status. Methods This was a national multicenter cross-sectional observational study that was conducted by 18 glaucoma experts in France. Patients over 18 years of age and receiving monotherapy with topical PG analogues for the treatment of ocular hypertension and/or glaucoma, with no history of prior glaucoma surgery, were consecutively selected from the glaucoma outpatient clinics of participating physicians and underwent an ocular surface examination. Results A total of 344 eyes of 344 patients were enrolled between November 2022 and November 2023. Prescribed PG monotherapy was PF in 271 (78.7%) patients. Clinical history and ocular surface evaluation indicated that 79.4% of the study population (n = 273) presented with at least one symptom or clinical sign of dry eye and that three patients out of four had an unstable tear film. Subgroup analysis comparing preserved and PF PG analogues showed a higher prevalence of conjunctival hyperemia and corneal staining in the preserved group. Multivariate analysis identified conjunctival hyperemia as consistently associated with preservative use (odds ratio = 7.654; p = 0.003 for moderate conjunctival hyperemia). Conclusions This study highlights the growing trend toward PF PG analogue prescriptions by specialists in France. However, ocular surface issues remain prevalent, impacting patient adherence and treatment efficacy. Comprehensive ocular surface examinations are crucial in glaucoma management to enhance long-term tolerance, compliance, and overall treatment success.