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This paper presents a model of recurrent multinomial sequences. Though there exists a quite considerable literature on modeling autocorrelation in numerical data and sequences of categorical outcomes, there is currently no systematic method of modeling patterns of recurrence in categorical sequences. This paper develops a means of discovering recurrent patterns by employing a more restrictive Markov assumption. The resulting model, which I call the recurrent multinomial model, provides a parsimonious representation of recurrent sequences, enabling the investigation of recurrences on longer time scales than existing models. The utility of recurrent multinomial models is demonstrated by applying them to the case of conversational turn-taking in meetings of the Federal Open Market Committee (FOMC). Analyses are effectively able to discover norms around turn-reclaiming, participation, and suppression and to evaluate how these norms vary throughout the course of the meeting. more...

Abstract Background The objective of this research was the development and evaluation of 203Pb-labelled panitumumab (203Pb-PSC-panitumumab) as an immuno-SPECT radioligand for the detection of EGFR + head and neck squamous cell carcinoma (HNSCC) in a patient-derived xenograft (PDX) mouse model. The 51.9 h physical half-life and favourable γ-emission (279 keV; 81%) of 203Pb offer an excellent opportunity for developing immuno-SPECT radioligands. Moreover, 203Pb has a complementary therapeutic radionuclide (212Pb), making 203Pb and 212Pb an ideal matched radiotheranostic pair. Results Radiolabeling of panitumumab was performed at a pH of 5.0 and room temperature for 5–10 min with [203Pb]Pb(OAc)2, and the incorporation efficiency was determined using radio-TLC. 203Pb-PSC-panitumumab (~ 10 MBq, 140 μl of saline) was injected into the tail vein of NRG mice bearing subcutaneous (s.c.) HNSCC patient-derived xenografts (PDX). SPECT/CT images were acquired at 48 and 120 h post-injection. For biodistribution studies, mice were euthanized five days after 203Pb-panitumumab injection. The tumour and normal tissues were collected and weighed, and uptake of 203Pb was measured in a γ-counter. The uptake was calculated as the percent injected dose per gram of each tissue (ID%/g). Blocking experiments were performed by pretreating a group of mice (n = 5) with 1 mg of panitumumab 1 h before administering 203Pb-PSC-panitumumab. 4–5 chelators of a new lead-specific chelator (PSC) were attached per antibody; radiolabeling efficiency was 99.2 ± 0.7%. The isolated radiochemical yield of 203Pb-PSC-panitumumab was 41.4 ± 8% (n = 5), and the molar activity was 1.2 ± 0.35 GB/mg. SPECT imaging and biodistribution confirmed high accumulation and retention of 203Pb-PSC-panitumumab in the tumour (26% ID/g) at 120 h post-injection (p.i.), which could be reduced to 6.2%ID/g at 120 h p.i. by predosing with panitumumab (1 mg) confirming EGFR specificity of 203Pb-PSC-panitumumab uptake. Conclusions Panitumumab was successfully and reproducibly labelled with 203Pb in high radiochemical purity using the chelator PSC-NCS. 203Pb-PSC-panitumumab was specifically accumulated and retained in EGFR + tumours in NRG mice with s.c. HNSCC PDX. 203Pb-PSC-panitumumab is a suitable immuno-SPECT radioligand for imaging EGFR + tumours and has great potential for combining with 212Pb-PSC-panitumumab in a radiotheranostic strategy for imaging and treating HNSCC. more...

Investigating the historical patterns of urban growth and their drivers is crucial to informing sustainable urban planning policies, especially in cities of the Global South. In Vietnam, most studies focus primarily on city extents, offering little insight into urban growth across various provinces. This study, therefore, combined categorical land use and land cover change detection, Random Forest classification and expert interviews to quantify the urban growth between 2000 and 2020, assess urban encroachment upon other land uses, and identify key drivers shaping this growth in Thua Thien Hue province. Findings show that the urban land areas were 27.94 km2, 82.97 km2, and 209.80 km2 in 2000, 2010, and 2020, respectively. Urban encroachment upon other land use types, especially cropland, barren land, rice paddies, shrubs, and forests, was observed in these periods. Additionally, accessibility to built-up areas, DEM, proximity to rice paddies, slope, proximity to street roads, accessibility to social areas, and proximity to cropland are the major spatial drivers of urban growth in the province. The study concludes that rapid urban expansion is evident in the province at the expense of other land use types, especially agricultural land use types, which may impact food security and livelihoods in the province. more...

Forest fires diminish forests’ ecological services, including carbon sequestration, water retention, air cooling, and recreation, while polluting the environment and endangering habitats. Despite considerable economic advancements, firefighting strategies remain less than optimal. This paper introduces the Bi-layer Predictive Ensemble (BIPE), an innovative machine learning model designed to enhance the accuracy and generalization of forest fire susceptibility mapping. BIPE integrates model-centric and data-driven strategies, employing automated methods such as 10-fold cross-validation and meta-learning to improve stability and generalization. During its 10-fold cross-validation, BIPE demonstrated excellent performance, with the Area Under the Curve (AUC) values ranging from 0.990 to 0.996 and accuracy levels consistently high, around 97%, underscoring its robust class separation ability and strong generalization across different datasets. Our results confirm that BIPE outperforms traditional high-performance models like Support Vector Machine (SVM), Multilayer Perceptron (MLP), Extreme Gradient Boosting (XGBoost), Deep Neural Network (DNN), and Convolutional Neural Network (CNN), showcasing its practical effectiveness and reliability on the data of nonlinear, high-dimensional, and complex interactions. Additionally, our forest fire susceptibility maps offer valuable complementary information for German forest fire management authorities, enhancing their ability to assess and manage fire risks more effectively. more...

Magnetic levitation (maglev) offers unique opportunities for guided transport; however, only a few existing maglev systems have demonstrated their potential benefits. This paper explores the potential of maglev-derived systems (MDS) in conventional rail, focusing on the use of linear motors to enhance freight operations. Such traction boosters provide additional propulsion capabilities by reducing the train consist’s dependence on wheel–rail adhesion and improving performance without needing an additional locomotive. The study analyses the Gothenburg–Borås railway in Sweden, a single-track, mixed-traffic line with limited capacity and slow speeds, where installing linear motors on uphill sections would allow freight trains to match the performance of passenger trains, even under challenging adhesion conditions. Target speed profiles were precomputed using dynamic programming, while a model predictive control algorithm determined the optimal train state and control trajectories. The results show that freight trains can achieve desired speeds but at the cost of increased energy consumption. A system-level cost–benefit analysis reveals a positive impact with a positive benefit-to-cost ratio. Although energy consumption increases, the time savings and reduced CO2 emissions from shifting goods from road to rail demonstrate substantial economic and environmental benefits, improving the efficiency and sustainability of rail freight traffic. more...

Abstract For the first time, the severed right hands of 12 individuals have been analysed osteologically. The hands were deposited in three pits within a courtyard in front of the throne room of a 15th Dynasty (c.1640–1530 BC) Hyksos palace at Avaris/Tell el-Dab‘a in north-eastern Egypt. Although this kind of practice is known from tomb or temple inscriptions and reliefs from the New Kingdom onwards, this is the first time that physical evidence has been used to learn more about the procedure and the individuals whose hands were taken. Here, we show that the right hands belonged to at least 12 adults, 11 males, and possibly one female. It is unclear if the hands were taken from dead or living individuals. After removing any attached parts of the forearm, the hands were placed in the ground with wide-splayed fingers, mainly on their palmar sides. The osteological analysis not only supports the archaeological interpretation of this evidence but also adds more detail regarding trophy-taking practices in Ancient Egypt. more...

Thousands of industrial sites were found to be correlated with contaminated sites in the Arctic. Between 13,000 and 20,000 contaminated sites are likely to exist in the permafrost region, 26% of which will be affected by permafrost thaw before 2100. more...

Background: A careful, often life-long, medication regimen is central to therapy for Inflammatory Bowel Disease (IBD) - a chronic gut disorder. Hence, medication adherence (MA) – patients taking medications in line with prescription – is important. Previous research indicates that a third of patients with IBD in southern New Zealand have poor medication adherence (MA). Objective: This study investigated these patients' experiences to determine factors that influence their MA, for the first time. Methods: Two focus group discussions (FGDs) were held with IBD patients in Otago, New Zealand. Reflexive thematic analysis from a ‘direct realist’ viewpoint was used to analyse the data. Results: Data were analysed in three segments: perceptions, experiences and support. Participants perceived MA as a “duty” that was very important to their wellbeing. The participants' MA was centred around a routine requiring proactivity to maintain. MA was negatively impacted by side effects and regimen factors including (high) pill numbers/dose frequency, and getting refills was framed as challenging; whilst healthcare professionals were presented as major MA facilitators. Lastly, the support structures identified included family, friends and colleagues as well as targeted health system factors e.g. medication subsidies. Conclusions: Factors spanning those related to the patients, their socioeconomic status, the disease, IBD therapy and the health system were presented as influencing IBD patients' MA in southern NZ. Thus, multifaceted interventions are needed across the health system to overcome the inhibiting and promote the facilitating elements. more...

For microscopic investigation, archaeological bone samples are often embedded in Biodur® epoxy resin. This study wants to test whether it is possible to extract DNA suitable for PCR amplification from this sample type. For eight individuals a set of samples – each consisting of a Biodur-embedded femur sample, a native femur sample and a control sample of different anatomical origin – were submitted to organic DNA extraction. The extraction success was tested by autosomal short tandem repeat amplification. Seven out of eight Biodur-embedded femur samples revealed successful amplification results. If Biodur-embedded bone material exists from earlier microscopic investigations, our results encourage the use of this sample type as a source for genetic research. more...

Abstract Background The amplitude-integrated EEG (aEEG) is a widely used monitoring tool in neonatology / pediatric intensive care. It takes into account the amplitudes, but not the frequency composition, of the EEG. Advantages of the aEEG are clear criteria for interpretation and time compression. During the first year of life, the electroencephalogram (EEG) during sedation / anesthesia changes from a low-differentiated to a differentiated EEG; higher-frequency waves develop increasingly. There are few studies on the use of aEEG during pediatric anesthesia. A systematic evaluation of the aEEG in defined EEG stages during anesthesia / sedation is not yet available. Parameters of pediatric EEGs (power, median frequency, spectral edge frequency) recorded during anesthesia and of the corresponding aEEGs (upper and lower value of the aEEG trace) should be examined for age-related changes. Furthermore, it should be examined whether the aEEG can distinguish EEG stages of sedation / anesthesia in differentiated EEGs. Methods In a secondary analysis of a prospective observational study EEGs and aEEGs (1-channel recordings, electrode positions on forehead) of 50 children (age: 0–18 months) were evaluated. EEG stages: A (awake), Slow EEG, E2, F0, and F1 in low-differentiated EEGs and A (awake), B0–2, C0–2, D0–2, E0–2, F0–1 in differentiated EEGs. Results Median and spectral edge frequency increased significantly with age (p more...

The increasing need for dynamic in-flight adjustments of a trajectory allows the airport, air traffic control and the airline a high degree of flexibility in terms of in-flight execution. This concept enables numerous optimisation options to jointly meet the requirements of sustainable air transport to increase economic and ecological efficiency, as well as safety. One promising measure is to control the aircraft arrival rate to prevent over-demand in the approach sector around the airport. In so-called Long-Range Air Traffic Management, the arrival time of long-haul flights, in particular, is already controlled many hours before arrival. However, the control options and their effects on arrival time and fuel burn are heavily dependent on flight performance and the (hardly predictable) influence of the weather. In this study, we optimize the arrival time of 26 long-haul flights in the Asia-Pacific region with arrival at Changi Airport within a peak hour considering the arrival rate of medium-haul and short-haul flights. This control is done by speed adjustments and by choosing alternative routes. For the first time, we model each long-haul flight and its control options individually in real weather conditions. We found that speed adjustments should start three to four hours before arriving at the approach sector to maximize the fuel-saving potential of small deviations from the optimal cruising speed, considering the predictability of the arrival time under real weather conditions. Allowing the aircraft to additionally choose an alternative lateral route, different from the filed flight plan, both maximizes the potential for harmonization of the number of aircraft in the approach sector and minimizes the total fuel burn. Unlike speed adjustments, alternative routes changes are effective even during the last hour of the cruise phase. more...

Abstract Objective Human intestinal organoids (hIOs) have potential as a model for investigating intestinal diseases. The hIO system faces logistic challenges including limited access to biopsies or low expression of epithelial cell types. Previous research identified the feasibility of tissue from the transverse (TC) or sigmoid colon (SC), or from cryopreserved biopsies from regions of the gastrointestinal tract. We aimed to create a protocol for robust hIO generation that could be implemented across multiple centres, allowing for development of a consistent biobank of hIOs from diverse patients. Results TC and SC hIOs were expanded from fresh or frozen biopsies with standard or refined media. The expression of epithelial cells was evaluated via PCR. Growth of TC and SC hIO from healthy donors was reproducible from freshly acquired and frozen biopsies. A refined media including insulin-like growth factor (IGF)-1 and fibroblast growth factor (FGF)-2 enabled the expression of epithelial cells, including higher expression of goblet cells and enterocytes compared to standard organoid media. We identified a consistent time point where hIOs generated from frozen biopsies reflect similar hIO composition from freshly acquired samples. Feasibility of hIOs as a tool for research and clinical use, including the use of frozen biopsies, was demonstrated. more...

Free route airspace allows airspace users to freely plan a route in en-route airspaces within certain restrictions. It is anticipated to offer the benefit of fuel saving and operational flexibility. Regarding its efficient implementation into the ASEAN airspace, the key challenge would be reducing hotspots with clusters of potential conflicts. This paper designed a time-varying queuing network model, which contributed to untangle trajectory complexity in the most congested hotspot area. A series of fast-time simulation experiments were conducted to identify hotspots in en-route airspace in Singapore FIR. The application of departure time control using time-varying queuing networks successfully reduced up to 45% of potential conflicts. This was achieved within an average delay of 30 min by controlling time of less than 60% of candidate flights. The original contribution of this paper is to develop a novel modeling and simulation framework for composing ideal air traffic patterns. Lastly, we discussed the extension of this study toward a generalized application of the proposed approach in future air traffic management. more...

In the face of growing 21st-century urban challenges, this study emphasizes the role of remote sensing data in objectively defining urban structure types (USTs) based on morphology. While numerous UST delineation approaches exist, few are universally applicable due to data constraints or impractical class schemes. This article attempts to tackle this challenge by summarizing important approaches dealing with the computation of USTs and to condense their contributions to the field of research within a single comprehensive framework. Hereby, this framework not only serves as a conjunctive reference for currently existing implementations, but is also independent regarding the input data, spatial scale, or targeted purpose of the mapping. It consists of four major steps: (1) the collection of suitable data sources to describe the building morphology as a key input, (2) the definition of a spatial mapping unit, (3) the parameterization of the mapping units, and (4) the final classification of the mapping units into urban structure types. We outline how these tasks can lead to a UST classification which fits the users’ needs based on their available input data. At the same time, the framework can serve as a protocol for future studies where USTs are mapped, or new approaches are presented. This article closes with an application example for three different cities to underline the flexibility and applicability of the proposed framework while maintaining maximized objectivity and comparability. We recommend this framework as a guideline for the use-specific mapping of USTs and hope to contribute to past and future research on this topic by fostering the implementation of this concept for the spatial analysis and a better understanding of complex urban environments. more...

Abstract This paper presents the earliest evidence for the exploitation of lignite (brown coal) in Europe and sheds new light on the use of combustion fuel sources in the 2nd millennium BCE Eastern Mediterranean. We applied Thermal Desorption/Pyrolysis–Gas Chromatography-Mass Spectrometry and Polarizing Microscopy to the dental calculus of 67 individuals and we identified clear evidence for combustion markers embedded within this calculus. In contrast to the scant evidence for combustion markers within the calculus samples from Egypt, all other individuals show the inhalation of smoke from fires burning wood identified as Pinaceae, in addition to hardwood, such as oak and olive, and/or dung. Importantly, individuals from the Palatial Period at the Mycenaean citadel of Tiryns and the Cretan harbour site of Chania also show the inhalation of fire-smoke from lignite, consistent with the chemical signature of sources in the northwestern Peloponnese and Western Crete respectively. This first evidence for lignite exploitation was likely connected to and at the same time enabled Late Bronze Age Aegean metal and pottery production, significantly by both male and female individuals. more...

Introduction and Objective: Despite the known benefits of physical activity in the management of chronic diseases, the use of exercise as a treatment is relatively underemployed, with many patients reporting their disease to be a barrier. This study aimed to assess physical activity levels, attitudes, and barriers towards exercise in a cohort of patients with inflammatory bowel disease (IBD). In addition, this study aimed to assess possible relationships between physical well-being, psychological well-being, and sociodemographic factors. Methods: 306 patients >18 years with diagnosed IBD in Dunedin, New Zealand, were approached to participate in this study. Participants who consented completed questionnaires regarding exercise preferences and attitudes, physical activity levels, and psychological well-being. Results: Seventy-seven patients participated in the study (77/308 = 25%). Sixty-six percent of participants met physical activity guidelines and the median metabolic equivalent minutes/week of 1,027.5 (505.5–2,339.5). Walking was the most preferred activity (30%) followed by water-based exercise (20%). Two-thirds of participants reported their disease limited the amount of physical activity undertaken. Common barriers to participating in physical activity included fatigue (34%) and abdominal pain (20%). Patients with active disease reported higher levels of barriers than those in remission (80 vs. 54%, p = 0.018). Higher physical activity levels were correlated with lower levels of fatigue (p = 0.022–0.046). Conclusions: While patients with IBD in Dunedin, New Zealand, are physically active, reducing real and perceived barriers is crucial to further increase physical activity in patients with IBD who are in remission or with active disease. more...

Abstract A multitude of recent studies have detailed microplastic concentrations in aquatic and terrestrial environments, although questions remain over their ultimate fate. At present, few studies have detailed microplastic characteristics and abundance along a freshwater–marine interface, and considerable uncertainties remain over the modelled contribution of terrestrial and riverine microplastic to the world’s oceans. In this article, for the first time, we detail sedimentary microplastic concentrations along a River–Sea transect from the lower reaches of a major continental river, the River Danube, through the Danube Delta, the Black Sea coast to the Romanian and Bulgarian inner shelf of the Black Sea. Our results indicate that isolated areas of the Danube Delta are still relatively pristine, with few microplastic particles in some of the sediments sampled. more...

Abstract Background and Aim Ostomy is a radical treatment that is sometimes required due to severe inflammatory bowel disease (IBD), colorectal cancer (CRC), and so on. Around 8000 people in New Zealand live with stoma bags. We studied factors associated with poor quality of life (QoL) in ostomy patients to improve patient care. Methods Eligible adult patients identified through the Southern District Health Board database were invited to participate. The survey consisted of the general stoma QoL, IBD, CRC QoL, and dietary and lifestyle questionnaires. Results Response rate was 54.5% (n = 241/448). Study participants were a mean (SD) 70.9 (14.2) years old, 60.6% were male, and 89.5% were New Zealand European; 52.5% of the study participants had a colostomy, and 56.4 and 22.4% received their stoma due to CRC and IBD, respectively. Median (first–third interquartile range) duration since ostomy for overall study sample was 6.9 (3.3–15.1) years. Mean (SD) Stoma‐QoL score for all the patients was 60.3 (10.8) points (scale 20–80). Stoma‐underlying disease (P = 0.28) and type of stoma (P = 0.60) were not associated with Stoma‐QoL scores. Older adults had higher Stoma‐QoL, IBD questionnaire and QLQ‐C30 quality‐of‐life scores; 73.1% received dietary recommendations for the stoma, And 56.4% changed their diet, 51.4% found it easy to adhere to dietary recommendations, and 9.2% found it quite/very difficult. Conclusion This study found high‐quality life scores in postostomy patients and no significant association between the underlying disease, time since ostomy, level of comorbidities, and how the appliance worked, which highlight the multifactorial nature of the quality of life concept and difficulties measuring it. more...

Background and Aim Breath testing (BT) is used to identify carbohydrate malabsorption and small intestine bacterial overgrowth. Measuring methane alongside hydrogen is advocated to reduce false‐negative studies, but the variability of methane production is unknown. The aim of this study is to examine the effect of high methane production on hydrogen excretion after ingesting lactulose, fructose, or lactose. Methods A retrospective audit was performed of patients with gastrointestinal symptoms who underwent BT. Following a low fermentable carbohydrate diet for 24‐h, a fasting BT before consuming 35 ml lactulose, 35 g fructose, or lactose in 200 ml water, followed by BT every 10–15 min for up to 3‐h, was performed. A positive test was defined as a ≥20 ppm rise of hydrogen or methane from baseline. A high methane producer had an initial reading of ≥5 ppm. Breath hydrogen and methane production were measured as area under the curve. Chi‐squared tests were used to compare proportions of those meeting the cut‐off criteria. Results Of patients, 26% (28/106) were high methane producers at their initial lactulose test. The test–retest repeatability of methane production was high, with the same methane production status before ingesting lactose in all (70/70) and before ingesting fructose in most (71/73). Methane production was highly variable during testing, with 38% (10/26) having ≥1 reading lower than baseline. Hydrogen produced by high or low methane producers did not differ (1528 [960–3645] ppm min vs 2375 [1810–3195] ppm min [P = 0.11]). Symptoms and breath test results were not positively related. Conclusion The validity of including an increase of ≥20 ppm methane to identify carbohydrate malabsorption or small intestine bacterial overgrowth should be questioned due to the variability of readings during testing. more...

Humans rely on clean water for their health, well-being, and various socio-economic activities. During the past few years, the COVID-19 pandemic has been a constant reminder of about the importance of hygiene and sanitation for public health. The most common approach to securing clean water supplies for this purpose is via wastewater treatment. To date, an effective method of detecting wastewater treatment plants (WWTP) accurately and automatically via remote sensing is unavailable. In this paper, we provide a solution to this task by proposing a novel joint deep learning (JDL) method that consists of a fine-tuned object detection network and a multi-task residual attention network (RAN). By leveraging OpenStreetMap (OSM) and multimodal remote sensing (RS) data, our JDL method is able to simultaneously tackle two different tasks: land use land cover (LULC) and WWTP classification. Moreover, JDL exploits the complementary effects between these tasks for a performance gain. We train JDL using 4,187 WWTP features and 4,200 LULC samples and validate the performance of the proposed method over a selected area around Stuttgart with 723 WWTP features and 1,200 LULC samples to generate an LULC classification map and a WWTP detection map. Extensive experiments conducted with different comparative methods demonstrate the effectiveness and efficiency of our JDL method in automatic WWTP detection in comparison with single-modality/single-task or traditional survey methods. Moreover, lessons learned pave the way for future works to simultaneously and effectively address multiple large-scale mapping tasks (e.g., both mapping LULC and detecting WWTP) from multimodal RS data via deep learning. more...

Background and study aims Mallory Weiss tears (MWTs) are relatively uncommon causes of upper gastrointestinal bleeding (UGIB), and patients are generally considered at low risk of poor outcome, although data are limited. There is uncertainty about use of endoscopic therapy. We aimed to describe and compare an international cohort of patients presenting with UGIB secondary to MWT and peptic ulcer bleeding (PUB). Patients and methods From an international dataset of patients undergoing endoscopy for acute UGIB at seven hospitals, we assessed patients with MWT bleeding, including the endoscopic stigmata and endoscopic therapy applied. We compared baseline parameters, rebleeding rate, and 30-day mortality between patients with MWT and PUB. Results A total of 3648 patients presented with UGIB, 125 of whom (3.4 %) had bleeding from a MWT. Those patients were younger (61 vs 69 years, P more...

Abstract Objectives Crohn's disease (CD) initiation and pathogenesis are believed to involve an environmental trigger in a genetically susceptible person that results in an immune response against commensal gut bacteria, leading to a compromised intestinal epithelial barrier and a cycle of inflammation. However, it has been difficult to study the contribution of all factors together in a physiologically relevant model and in a heterogenous patient population. Methods We developed an autologous colonic monolayer model that incorporated the immune response from the same donor and a commensal bacteria, Faecalibacterium prausnitzii. Two‐dimensional monolayers were grown from three‐dimensional organoids generated from intestinal biopsies, and the epithelial integrity of the epithelium was measured using transepithelial electrical resistance. We determined the effect of immune cells alone, bacteria alone and the co‐culture of immune cells and bacteria on integrity. Results Monolayers derived from CD donors had impaired epithelial integrity compared to those from non‐inflammatory bowel disease (IBD) donors. This integrity was further impaired by culture with bacteria, but not immune cells, despite a higher frequency of inflammatory phenotype peripheral T cells in CD donors. Variability in epithelial integrity was higher in CD donors than in non‐IBD donors. Conclusion We have developed a new autologous model to study the complexity of CD, which allows for the comparison of the barrier properties of the colonic epithelium and the ability to study how autologous immune cells directly affect the colonic barrier and whether this is modified by luminal bacteria. This new model allows for the study of individual patients and could inform treatment decisions. more...

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Large-scale mapping activities can benefit from the vastly increasing availability of earth observation (EO) data, especially when combined with volunteered geographical information (VGI) using machine learning (ML). High-resolution maps of inland surface water bodies are important for water supply and natural disaster mitigation as well as for monitoring, managing, and preserving landscapes and ecosystems. In this paper, we propose an automatic surface water mapping workflow by training a deep residual neural network (ResNet) based on OpenStreetMap (OSM) data and Sentinel-2 multispectral data, where the Simple Non-Iterative Clustering (SNIC) superpixel algorithm was employed for generating object-based training samples. As a case study, we produced an open surface water layer for Germany using a national ResNet model at a 10 m spatial resolution, which was then harmonized with OSM data for final surface water products. Moreover, we evaluated the mapping accuracy of our open water products via conducting expert validation campaigns, and comparing to existing water products, namely the WasserBLIcK and Global Surface Water Layer (GSWL). Using 4,600 validation samples in Germany, the proposed model (ResNet+SNIC) achieved an overall accuracy of 86.32% and competitive detection rates over the WasserBLIcK (87.47%) and GSWL (98.61%). This study provides comprehensive insights into how to best explore the synergy of VGI and ML of EO data in a large-scale surface water mapping task. more...

Objective: To analyze continuous 1- or 2-channel electroencephalograms (EEGs) of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) with regard to occurrence of epileptiform potentials.Design: Single-center retrospective analysis.Setting: Intensive care unit of Hannover Medical School, Hannover, Germany.Patients: Critically ill COVID-19 patients who underwent continuous routine EEG monitoring (EEG monitor: Narcotrend-Compact M) during sedation.Measurements and Main Results: Data from 15 COVID-19 patients (11 men, four women; age: 19–75 years) were evaluated. Epileptiform potentials occurred in 10 of 15 patients (66.7%).Conclusions: The results of the evaluation regarding the occurrence of epileptiform potentials show that there is an unusually high percentage of cerebral involvement in patients with severe COVID-19. EEG monitoring can be used in COVID-19 patients to detect epileptiform potentials. more...

Abnormally pronounced digital impressions (APDIs) on the endocranial surface develop secondary to a prolonged rise in the intracranial pressure. This can result from a number of pathological conditions, including hydrocephalus due to tuberculous meningitis (TBM). APDIs have been described with relation to TBM not only in the modern medical literature but also in several paleopathological studies. However, APDIs are not pathognomonic for TBM and their diagnostic value for identifying TBM in past human populations has not been evaluated in identified pre-antibiotic era skeletons. To assess the diagnostic value of APDIs for the first time, a macroscopic investigation was performed on skeletons from the Terry Collection (Smithsonian Institution, Washington, DC, USA). Our material consisted of 234 skeletons with tuberculosis (TB) as the cause of death (TB group) and 193 skeletons with non-tuberculous (NTB) causes of death (NTB group). The macroscopic examination focused on the stage of the prominence and frequency of APDIs in the TB group and NTB group. To determine the significance of difference (if any) in the frequency of APDIs between the two groups, χ2 testing of our data was conducted. We found that APDIs were twice as common in the TB group than in the NTB group. The χ2 comparison of the frequencies of APDIs revealed a statistically significant difference between the two groups. In addition, APDIs with more pronounced stages were recorded more frequently in the TB group. Our results indicate that APDIs can be considered as diagnostic criteria for TBM in the paleopathological practice. With suitable circumspection, their utilization provides paleopathologists with a stronger basis for identifying TB and consequently, with a more sensitive means of assessing TB frequency in past human populations. more...

Objective To explore how adults living with inflammatory bowel disease (IBD) in rural New Zealand manage their condition and engage with healthcare providers.Design Qualitative exploratory design with semi-structured interviews analysed thematically.Setting and participants Interviews were conducted with 18 people living with IBD in the Otago region of the South Island.Results Five important constructs were identified: (1) journey to confirming and accepting diagnosis; (2) importance of the relationship with the healthcare team; (3) support from others; (4) learning how to manage IBD and (5) care at a distance—experiences of rurality. Pathways to confirming diagnosis involved two contrasting journeys: a long and slow process where diagnosis remained unclear for a prolonged period, and a more acute process where diagnosis typically came as a shock. Central to the acceptance process was acknowledging the chronicity of the condition, which involved feelings of grief but also the fear of judgement and stigma. Building a strong relationship with the specialist was central to medical management, particularly in the initial stage following diagnosis. Support from others was critical, enabling participants to progress through acceptance of the disease and developing confidence in its everyday management. Participants shared different strategies on how to manage IBD, describing a ‘trial and error’ process of ‘finding what is right’ at different stages of the condition. Managing IBD rurally involved challenges of access to specialist care, with perceptions of delayed referrals and concerns about disparities in specialist access compared with urban counterparts. Rural living also had financial implications—cost of time and cost of mobilising resources for long travels to the urban centre for treatments.Conclusions Findings from this study provide a rich understanding of the complex health journeys of people living with IBD and the challenges of managing the condition rurally. more...

Abstract Epithelial-to-mesenchymal transition (EMT) is implicated in cancer metastasis and drug resistance. Specifically targeting cancer cells in an EMT-like state may have therapeutic value. In this study, we developed a cell imaging-based high-content screening protocol to identify EMT-selective cytotoxic compounds. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. The mechanism of action of monensin was further evaluated. Monensin (10 nM) induced apoptosis, cell cycle arrest, and an increase in reactive oxygen species (ROS) production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus and perturbed mitochondrial function. These are previously known effects of monensin, albeit occurring at much higher concentrations in the micromolar range. The cytotoxic effect of monensin was not blocked by inhibitors of ferroptosis. To explore the generality of our findings, we evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC50 cutoff of 100 nM. Gene Set Enrichment Analysis identified EMT as the top enriched gene set in the sensitive group. Importantly, increased monensin sensitivity in EMT-like cells is associated with elevated uptake of 3H-monensin compared to resistant cells. more...