Search

Abstract Powdery mildew outbreaks, caused by Podosphaera xanthii, cause reduced watermelon yields as the plants produce fewer and smaller fruits due to premature leaf senescence. The reduced leaf canopy can decrease fruit quality due to sun scalding. Sources of powdery mildew tolerance were previously identified by screening the USDA Citrullus germplasm collection with P. xanthii races 1 W and 2 W. However, not all gene loci associated with tolerance to race 2 W have been identified and markers tightly linked to such loci have not been developed. We employed a bulked segregant analysis approach using historical data from the USDA Germplasm Resource Information Network for an extreme-phenotype genome-wide association study (XP-GWAS) of tolerance to P. xanthii race 2 W in Citrullus accessions (N = 1,147). XP-GWAS identifies variants that segregate between pools of individuals chosen from the extremes of a phenotypic distribution from a diversity panel. Whole-genome resequencing of 45 individuals bulked from tolerant and susceptible extremes resulted in 301,059 high-quality biallelic SNPs. Two adjacent SNPs on chromosome 7 were significantly associated with P. xanthii race 2 W tolerance in the bulks and two additional SNPs had a strong signal in the XP-GWAS analysis. Kompetitive Allele-Specific PCR (KASP) markers were designed for sixteen SNPs across the three genomic regions. The KASP markers were validated by genotyping 186 accessions from the extremes of the disease response distribution of the Citrullus collection. Analysis of variance determined that thirteen of the markers were significantly associated, with the best marker in each region explaining 21–31% of the variation in powdery mildew tolerance.

Network utility maximization (NUM) addresses the problem of allocating resources fairly within a network and explores the ways to achieve optimal allocation in real-world networks. Although extensively studied in classical networks, NUM is an emerging area of research in the context of quantum networks. In this work, we consider the quantum network utility maximization (QNUM) problem in a static setting, where a user's utility takes into account the assigned quantum quality (fidelity) via a generic entanglement measure, as well as the corresponding rate of entanglement generation. Under certain assumptions, we demonstrate that the QNUM problem can be formulated as an optimization problem with the rate allocation vector as the only decision variable. Using a change-of-variable technique known in the field of geometric programming, we then establish sufficient conditions under which this formulation can be reduced to a convex problem: a class of optimization problems that can be solved efficiently and with certainty even in high dimensions. We further show that this technique preserves convexity, enabling us to formulate convex QNUM problems in networks where some routes have certain entanglement measures that do not readily admit convex formulation while others do. This allows us to compute the optimal resource allocation in networks where heterogeneous applications run over different routes.

Hygroscopicity strongly influences aerosol properties and multiphase chemistry, which is essential in several atmospheric processes. Although CCN (cloud condensation nuclei) properties are commonly measured, sub-saturated hygroscopicity measurements remain rare. During the ACROSS campaign (Atmospheric ChemistRy Of the Suburban foreSt, conducted in Paris in summer 2022), particles' hygroscopic growth rates at 90 % relative humidity (RH) and chemical composition were measured at the sub-urban site using a Hygroscopicity Tandem Differential Mobility Analyser (HTDMA, scanning at 100, 150, 200, and 250 nm) and an Aerodyne High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS). Growth factor probability density functions (GF-PDFs) revealed two distinct modes, namely hydrophobic and hygroscopic, suggesting a combination of internal and external particle mixing, with the split at GF 1.2. The prevalence of the hygroscopic mode increased with particle size, with mean hygroscopicity (κ) values of 0.23 and 0.38 for 100 and 200 nm particles, respectively. Using the Zdanovskii–Stokes–Robinson (ZSR) mixing rule, the agreement between measured and chemically derived hygroscopicity was approximately 51% for 100 nm particles, which declined for 200 and 250 nm. These emphasise the large effect of external particle mixing and its influence on predicting hygroscopicity. The ZSR approach proves to be unreliable in predicting the wide growth distribution of externally mixed particles. In this measurement, 80 %–90 % of the particles were externally mixed and influenced by fresh emission, which affected the hygroscopicity prediction by a factor of 2. A cluster analysis based on backward trajectories and meteorological conditions gives valuable insights into the chemical composition and variations in the hygroscopicity of different air masses.

For the past 20 years, reintroduction efforts have been underway to re-establish a migratory population of Northern Bald Ibises (Geronticus eremita) in Central Europe, which now consists of more than 250 birds. They breed both north and south of the Alps and migrate to a common wintering ground in Tuscany. Recently, the start of autumn migration has been increasingly delayed, which correlates with extended warm periods in autumn. Later in the year, however, the birds no longer find sufficient thermals to cross the Alps and remain in the northern Alpine foothills. In order to save their lives, we had to capture the affected birds before the onset of winter, which is not a sustainable solution. A new approach to solving the problem is the establishment of a second migration route to a wintering area in Andalusia, Spain, connecting our population with a sedentary population there. The new migration route bypasses mountain barriers and also allows the birds to reach the wintering grounds later in the year. The modelling of a pan-European population will provide the birds with high ecological and spatial flexibility. Our project exemplifies the consequences of advancing global warming for animal populations and the associated challenges for conservation projects.

Abstract Background Watermelon is a nutritionally and economically significant crop in the US and globally. Gummy Stem Blight (GSB), caused by three cryptic Stagonosporopsis species, is one of the most devastating diseases affecting watermelon in the US, impacting most of the plant’s above-ground parts. This study aimed to identify key Quantitative Trait Variants (QTVs) that include SNPs and In/Dels associated with GSB resistance in selfed derivatives of advanced multicross interspecific derivatives population derived from intercrosses between the most resistant lines of Citrullus amarus and highly susceptible cultivars of Citrullus lanatus. Results Resistant and susceptible bulks were created by combining equimolar DNA concentrations from 30 extremely resistant derivatives and 30 extremely susceptible lines. These bulks underwent whole-genome sequencing, generating over 1 billion reads per bulk to achieve comprehensive genome coverage. The mapping percentage of the bulks to the parental genomes ranged from 92 to 99%. More than 6 million SNPs and 1 million indels were identified from the resistant parental genome, compared to fewer than 2 million SNPs and 0.4 million indels from the susceptible parental genome. QTNs associated with GSB resistance were identified using single-nucleotide polymorphism-index and Gprime methods. Statistically significant variants/loci linked to GSB resistance were found on chromosomes 1, 2, 3, 5, 7, 10, and 11. Notably, the genes Lipase class 3 family protein, Ribosome hibernation promotion factor (CaU02G00010), Ubiquitin-like-specific protease 1D (CaU03G04260), and Zinc finger CCCH domain-containing 15 (CaU03G10970) harbored the highest delta SNPs. Several previously published genes, including Avr9/Cf-9 Rapidly Elicited Protein (CaU07G12990) on chromosome 7, were also identified. Conclusions Identifying significant loci associated with GSB resistance has facilitated the development of PACE assays, which will aid in breeding GSB-resistant watermelon cultivars. These findings provide critical insights into the genetic basis of GSB resistance and represent a significant step towards improving the resilience of watermelon crops against this devastating disease.

Reforestation through agroforestry is a common practice in the tropics but the political structures and processes as well as the ecological factors that define their outcomes need more attention. We employed mixed methods with insights from political ecology to enhance the understanding of agroforestry under the modified taungya system (MTS) in Ghana. The study reveals that the MTS is defined by governmentality and discursive power informed by the broader political economy. Specifically, economic and ecological factors intersect with environmental politics to inform the choice of tree species being used for the agroforestry. Additionally, the power dynamics across scale create differentiated access to degraded forest reserves and push less powerful people to the background. More so, power struggles, inhibiting structures, and politics of the sharing of tree revenue within the system contribute to some farmers devising illegal means to have, and maintain access, to degraded forest reserves which are creating negative consequences to the agroforestry initiative. We recommend that the Forestry Commission should (re)sensitise all forest-fringe communities, provide opportunities for a meaningful participation of all stakeholders of the MTS and sign the agreement on the sharing of tree revenue with participating farmers. It is also important that more women are targeted and assigned degraded forest reserves directly, as they are more compliant with the required practices of the MTS.

Introduction A novel focal cortex stimulation (FCS) device has recently received approval in Europe for patients with focal drug-resistant epilepsy (DRE). After 6 months of stimulation, 17 of 32 patients achieved ≥50% reduction in seizure frequency compared with their prestimulation baseline (responders). Currently, there is no established method for predicting FCS treatment response prior to implantation.Methods and analysis This is an ongoing combined retrospective-prospective non-interventional multicentre study. Clinical data of up to 100 patients treated with FCS are collected across 20 collaborating epilepsy centres in four European countries. The key outcome parameters, seizure frequency and severity, are measured along with metrics on cognition, mood and quality of life, both pre-electrode and postelectrode implantation. The data are complemented by demographics, medical history and information on antiseizure medication and FCS treatment parameters during the stimulation period. In addition to clinical data, MRI and electroencephalography registrations are used to gain insights into spatial and electrophysiological aspects of FCS. Multivariate statistical and machine learning analyses are employed to identify key predictive biomarkers associated with patient outcomes (responders vs non-responders). The primary goal is to improve counselling for DRE patients by identifying promising candidates for FCS treatment.Ethics and dissemination This study has received approval from the ethics committee of the University of Freiburg, Germany (23–1540 S1; 23–1183_1-S1-retro). The same approval is applicable for all participating centres in Germany as part of a multicentre study. Ghent University Hospital, Belgium, has received approval for participation in the retrospective arm from their local ethics committee (ONZ-2024-0168). The final approvals for the participating Swiss and Austrian sites are still pending. The results will be made available to the public through peer-reviewed journals and conference presentations.

Abstract Background The frequency and severity of abiotic stress events, especially drought, are increasing due to climate change. The plant root is the most important organ for water uptake and the first to be affected by water limitation. It is therefore becoming increasingly important to include root traits in studies on drought stress tolerance. However, phenotyping under field conditions remains a challenging task. In this study, plants were grown in a hydroponic system with polyethylene glycol as an osmotic stressor and in sand pots to examine the root system of eleven spring barley genotypes. The root anatomy of two genotypes with different response to drought was investigated microscopically. Results Root diameter increased significantly (p

Global warming is amplified in the Arctic. However, numerical models struggle to represent key processes that determine Arctic weather and climate. To collect data that help to constrain the models, the HALO–(𝒜𝒞)3 aircraft campaign was conducted over the Norwegian and Greenland seas, the Fram Strait, and the central Arctic Ocean in March and April 2022. The campaign focused on one specific challenge posed by the models, namely the reasonable representation of transformations of air masses during their meridional transport into and out of the Arctic via northward moist- and warm-air intrusions (WAIs) and southward marine cold-air outbreaks (CAOs). Observations were made over areas of open ocean, the marginal sea ice zone, and the central Arctic sea ice. Two low-flying and one long-range, high-altitude research aircraft were flown in colocated formation whenever possible. To follow the air mass transformations, a quasi-Lagrangian flight strategy using trajectory calculations was realized, enabling us to sample the same moving-air parcels twice along their trajectories. Seven distinct WAI and 12 CAO cases were probed. From the quasi-Lagrangian measurements, we have quantified the diabatic heating/cooling and moistening/drying of the transported air masses. During CAOs, maximum values of 3 K h−1 warming and 0.3 g kg−1 h−1 moistening were obtained below 1 km altitude. From the observations of WAIs, diabatic cooling rates of up to 0.4 K h−1 and a moisture loss of up to 0.1 g kg−1 h−1 from the ground to about 5.5 km altitude were derived. Furthermore, the development of cloud macrophysical (cloud-top height and horizontal cloud cover) and microphysical (liquid water path, precipitation, and ice index) properties along the southward pathways of the air masses were documented during CAOs, and the moisture budget during a specific WAI event was estimated. In addition, we discuss the statistical frequency of occurrence of the different thermodynamic phases of Arctic low-level clouds, the interaction of Arctic cirrus clouds with sea ice and water vapor, and the characteristics of microphysical and chemical properties of Arctic aerosol particles. Finally, we provide a proof of concept to measure mesoscale divergence and subsidence in the Arctic using data from dropsondes released during the flights.

Abstract Enteric glia have been recently recognized as key components of the colonic tumor microenvironment indicating their potential role in colorectal cancer pathogenesis. Although enteric glia modulate immune responses in other intestinal diseases, their interaction with the colorectal cancer immune cell compartment remains unclear. Through a combination of single-cell and bulk RNA-sequencing, both in murine models and patients, here we find that enteric glia acquire an immunomodulatory phenotype by bi-directional communication with tumor-infiltrating monocytes. The latter direct a reactive enteric glial cell phenotypic and functional switch via glial IL-1R signaling. In turn, tumor glia promote monocyte differentiation towards pro-tumorigenic SPP1+ tumor-associated macrophages by IL-6 release. Enteric glia cell abundancy correlates with worse disease outcomes in preclinical models and colorectal cancer patients. Thereby, our study reveals a neuroimmune interaction between enteric glia and tumor-associated macrophages in the colorectal tumor microenvironment, providing insights into colorectal cancer pathogenesis.

BackgroundCushing’s syndrome (CS) in dogs is mainly caused by pituitary-dependent (PDH) or adrenal-dependent (ADH) hypercortisolism. Result of the low-dose-dexamethasone suppression test (LDDST) with partial suppression (PSP) or escape pattern (EP) are indicative of PDH. No data concerning the ultrasonographic characteristics of the adrenal glands from dogs with these patterns exists.ObjectiveTo describe ultrasonographic appearance of adrenal glands in dogs with CS, with a LDDS test result consistent with PSP or EP.AnimalsForty-nine client owned dogs with a diagnosis CS with a PSP or EP in the LDDST.MethodsRetrospective evaluation of ultrasonographic adrenal gland size, shape and echogenicity. The dorsoventral thickness ratio (DVTR) and dorsoventral thickness difference ratio (DVTDR) was calculated.ResultsPSP and EP occurred in 42.9 and 57.1% of all LDDST. The median maximum width of the left adrenal gland was 0.71 cm (IQR, 0.24 cm) and of the right 0.75 cm (IQR, 0.19 cm) in all dogs and there was no difference between both patterns. There was a significant correlation between adrenal gland width and weight (left adrenal gland p = 0.002, right adrenal gland p = 0.017). In 9/49 dogs (18.4%), an adrenal asymmetry with a DVTDR >0.3 was present. In 7 of these 9 dogs, follow-up was available indicating presence of PDH.Conclusions and clinical importanceBased on follow up, PSP and EP of the LDDST were very supportive of PDH. Bilaterally symmetric adrenomegaly is a characteristic finding in dogs with PDH, however the size of adrenal gland width in this cohort was smaller than previously reported. Adrenal asymmetry was noted in approximately 20%.

The field of extreme event attribution (EEA) has rapidly developed over the last two decades. Various methods have been developed and implemented, physical modelling capabilities have generally improved, the field of impact attribution has emerged, and assessments serve as a popular communication tool for conveying how climate change is influencing weather and climate events in the lived experience. However, a number of non-trivial challenges still remain that must be addressed by the community to secure further advancement of the field whilst ensuring scientific rigour and the appropriate use of attribution findings by stakeholders and associated applications. As part of a concept series commissioned by the World Climate Research Programme, this article discusses contemporary developments and challenges over six key domains relevant to EEA, and provides recommendations of where focus in the EEA field should be concentrated over the coming decade. These six domains are: (1) observations in the context of EEA; (2) extreme event definitions; (3) statistical methods; (4) physical modelling methods; (5) impact attribution; and (6) communication. Broadly, recommendations call for increased EEA assessments and capacity building, particularly for more vulnerable regions; contemporary guidelines for assessing the suitability of physical climate models; establishing best-practice methodologies for EEA on compound and record-shattering extremes; co-ordinated interdisciplinary engagement to develop scaffolding for impact attribution assessments and their suitability for use in broader applications; and increased and ongoing investment in EEA communication. To address these recommendations requires significant developments in multiple fields that either underpin (e.g., observations and monitoring; climate modelling) or are closely related to (e.g., compound and record-shattering events; climate impacts) EEA, as well as working consistently with experts outside of attribution and climate science more generally. However, if approached with investment, dedication, and coordination, tackling these challenges over the next decade will ensure robust EEA analysis, with tangible benefits to the broader global community.

Abstract Objective Self‐management interventions may enhance health‐related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone‐delivered self‐care treatment program for adults with epilepsy. Methods The 12‐week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting‐list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy‐related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE‐31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi‐structured interviews were conducted with a heterogeneous sample of participants to assess user‐friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). Results Ninety‐two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. Significance Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self‐care apps. Feedback loops allow the participatory development of tailored interventions. Plain Language Summary In this study, we investigated the effectiveness of an app‐based self‐help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one‐fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

Systematic, routine, and comprehensive evaluation of Earth system models (ESMs) facilitates benchmarking improvement across model generations and identifying the strengths and weaknesses of different model configurations. By gauging the consistency between models and observations, this endeavor is becoming increasingly necessary to objectively synthesize the thousands of simulations contributed to the Coupled Model Intercomparison Project (CMIP) to date. The Program for Climate Model Diagnosis and Intercomparison (PCMDI) Metrics Package (PMP) is an open-source Python software package that provides quick-look objective comparisons of ESMs with one another and with observations. The comparisons include metrics of large- to global-scale climatologies, tropical inter-annual and intra-seasonal variability modes such as the El Niño–Southern Oscillation (ENSO) and Madden–Julian Oscillation (MJO), extratropical modes of variability, regional monsoons, cloud radiative feedbacks, and high-frequency characteristics of simulated precipitation, including its extremes. The PMP comparison results are produced using all model simulations contributed to CMIP6 and earlier CMIP phases. An important objective of the PMP is to document the performance of ESMs participating in the recent phases of CMIP, together with providing version-controlled information for all datasets, software packages, and analysis codes being used in the evaluation process. Among other purposes, this also enables modeling groups to assess performance changes during the ESM development cycle in the context of the error distribution of the multi-model ensemble. Quantitative model evaluation provided by the PMP can assist modelers in their development priorities. In this paper, we provide an overview of the PMP, including its latest capabilities, and discuss its future direction.

Abstract Extracellular matrix (ECM) deposition after central nervous system (CNS) injury leads to inhibitory scarring in humans and other mammals, whereas it facilitates axon regeneration in the zebrafish. However, the molecular basis of these different fates is not understood. Here, we identify small leucine-rich proteoglycans (SLRPs) as a contributing factor to regeneration failure in mammals. We demonstrate that the SLRPs chondroadherin, fibromodulin, lumican, and prolargin are enriched in rodent and human but not zebrafish CNS lesions. Targeting SLRPs to the zebrafish injury ECM inhibits axon regeneration and functional recovery. Mechanistically, we find that SLRPs confer mechano-structural properties to the lesion environment that are adverse to axon growth. Our study reveals SLRPs as inhibitory ECM factors that impair axon regeneration by modifying tissue mechanics and structure, and identifies their enrichment as a feature of human brain and spinal cord lesions. These findings imply that SLRPs may be targets for therapeutic strategies to promote CNS regeneration.

In this work, we compare the rate of warming of summertime extreme temperatures (summer maximum value of daily maximum temperature; TXx) relative to the local mean (summer mean daily maximum temperature; TXm) over the Northern Hemisphere in observations and one set of large ensemble (LE) simulations. During the 1979–2021 historical period, observations and simulations show robust warming trends in both TXm and TXx almost everywhere in the Northern Hemisphere, except over the eastern U.S. where observations show a slight cooling trend in TXx, which may be a manifestation of internal variability. We find that the observed warming rate in TXx is significantly smaller than in TXm in North Africa, western North America, Siberia, and Eastern Asia, whereas the warming rate in TXx is significantly larger over the Eastern U.S., the U.K., and Northwestern Europe. This observed geographical pattern is successfully reproduced by the vast majority of the LE members over the historical period, and is persistent (although less intense) in future climate projections over the 2051–2100 period. We also find that these relative warming patterns are mostly driven by the local hydroclimate conditions. TXx warms slower than TXm in the hyper-arid, arid, semi-arid and moist regions, where trends in the partitioning of the turbulent surface fluxes between the latent and sensible heat flux are similar during regular and extreme hot days. In contrast, TXx warms faster than TXm in dry-subhumid regions where trends in the partitioning of the surface fluxes are significantly different between regular and extreme hot days, with a larger role of sensible heat flux during the extreme hot days.

Abstract In this paper, we argue that a right-wing populist leader’s support of regional organizations depends on how domestic supporters are affected by populist engagement with them. If the regional organization does not affect groups of the populist project, then the leader enjoys latitude to question the regional institution. However, whenever undermining the regional organization damage a group, the leader does not target the regional organization, and assumes an ambivalent approach. We use the case of Bolsonaro’s Brazil engaging two regional organizations: MERCOSUR and PAHO to test our argument. Our findings reveal that right-wing populist leaders are aware of domestic costs.

In improvisational theatre (improv) dialog, characters, and story are created spontaneously by the actors on stage. Impro trainers posit that compelling stories in improv are the result of social creativity (as opposed to individual creativity), a process of social interaction in which every actor contributes small impulses to commonly create the story without individual intent. Hence, improv techniques which aim to foster this social creative process have gained increasing popularity and spread into fields beyond the performing arts (e.g., business trainings), claiming to improve, among other things, participants’ social interaction skills. However, these claims have barely been investigated empirically. Here, we compare improv-players with matched controls in a controlled adaptation of an improv paradigm to study how they handle expectation violations in a social interaction situation. This paradigm allows to insert experimentally intended expectation violations into a predetermined dialogue measure their response times to these violations. In Experiment 1, we investigated the suitability of the paradigm and in the pre-registered Experiment 2, we compared the performance of improv-players and controls. The results showed that controls seem to have more difficulties in dealing with unexpected than expected utterances than improv-players. Furthermore, we find that improv-players receive higher scores on creativity and tolerance of uncertainty. We conclude that our results present first humble evidence that the successful handling of expectation violations in social interaction situations is indeed pronounced in improv players and might hence contribute to the social creativity observed on the improv stage.

The magnetic dipole and the spectroscopic quadrupole moments of the nuclear ground states in the odd-mass nickel isotopes 59−67Ni have been determined using collinear laser spectroscopy at the CERN-ISOLDE facility. They are compared to ab initio valence-space in-medium similarity renormalization group (VS-IMSRG) calculations including contributions of two-body currents as well as to shell-model calculations. The two-body-current contributions significantly improve the agreement with experimental data, reducing the mean-square deviation from the experimental moments by a factor of 3 to 5, depending on the employed interaction. For all interactions, the largest contributions are obtained for the 52− (72−) isotopes 65Ni (55Ni), which is ascribed to the high angular momentum of the f orbitals. Our results demonstrate that the inclusion of two-body-current contributions to the magnetic moment in an isotopic chain of complex nuclei can be handled by the VS-IMSRG and can outperform phenomenological shell-model calculations using effective g-factors in the nickel region.

We aimed to explore the differences in immune checkpoint inhibitor (ICI) immunotherapy utilization for advanced melanoma by examining patient and neighborhood characteristics. We performed a retrospective cohort study using a deidentified, random sample of SEER-Medicare beneficiaries aged ≥65 years with stage III or stage IV melanoma (2011–2017). Our primary outcome was initiation of ICI immunotherapy (ipilimumab, pembrolizumab, nivolumab, or atezolizumab) after stage III or stage IV melanoma diagnosis. We analyzed ICI usage with multivariable logistic regression. After analyzing the entire 2011–2017 cohort, we conducted a secondary analysis in which we separately analyzed the 2011–2014 and 2015–2017 cohorts to assess possible differences over time. We included 3531 beneficiaries, with mean follow-up of 2.1 (SD = 2.0) years. Higher likelihood of ICI usage was associated with male sex (OR = 1.21, 95% confidence interval = 1.04–1.42) and higher density of medical oncologists (OR = 1.02, 95% confidence interval = 1.01–1.04). Lower likelihood of ICI usage was associated with older age group and Charlson comorbidity score (score ≥2; OR = 0.72, 95% confidence interval = 0.60–0.86). These associations were diminished in more recent years (no association with sex, medical oncologist density, Charlson comorbidity score, and association with only the oldest age group in years 2015–2017). We found significant sex- and age-related differences in initiation among SEER-Medicare beneficiaries with stage III or stage IV melanoma, which appear to be improving over time.

IntroductionEnteric glial cells are important players in the control of motility, intestinal barrier integrity and inflammation. During inflammation, they switch into a reactive phenotype enabling them to release inflammatory mediators, thereby shaping the inflammatory environment. While a plethora of well-established in vivo models exist, cell culture models necessary to decipher the mechanistic pathways of enteric glial reactivity are less well standardized. In particular, the composition of extracellular matrices (ECM) can massively affect the experimental outcome. Considering the growing number of studies involving primary enteric glial cells, a better understanding of their homeostatic and inflammatory in vitro culture conditions is needed.MethodsWe examined the impact of different ECMs on enteric glial culture purity, network morphology and immune responsiveness. Therefore, we used immunofluorescence and brightfield microscopy, as well as 3’ bulk mRNA sequencing. Additionally, we compared cultured cells with in vivo enteric glial transcriptomes isolated from Sox10iCreERT2Rpl22HA/+ mice.ResultsWe identified Matrigel and laminin as superior over other coatings, including poly-L-ornithine, different lysines, collagens, and fibronectin, gaining the highest enteric glial purity and most extended glial networks expressing connexin-43 hemichannels allowing intercellular communication. Transcriptional analysis revealed strong similarities between enteric glia on Matrigel and laminin with enrichment of gene sets supporting neuronal differentiation, while cells on poly-L-ornithine showed enrichment related to cell proliferation. Comparing cultured and in vivo enteric glial transcriptomes revealed a 50% overlap independent of the used coating substrates. Inflammatory activation of enteric glia by IL-1β treatment showed distinct coating-dependent gene expression signatures, with an enrichment of genes related to myeloid and epithelial cell differentiation on Matrigel and laminin coatings, while poly-L-ornithine induced more gene sets related to lymphocyte differentiation.DiscussionTogether, changes in morphology, differentiation and immune activation of primary enteric glial cells proved a strong effect of the ECM. We identified Matrigel and laminin as pre-eminent substrates for murine enteric glial cultures. These new insights will help to standardize and improve enteric glial culture quality and reproducibility between in vitro studies in the future, allowing a better comparison of their functional role in enteric neuroinflammation.

Abstract Objective The aims of the study were to (1) characterize the findings of flexible endoscopic evaluation of swallowing (FEES) in stroke patients undergoing mechanical thrombectomy (MT); (2) analyse the screening performance of the Standardized Swallowing Assessment (SSA); and (3) study the impact of FEES‐defined dysphagia on 3‐month outcomes. Methods This single‐centre study was based on a local registry of consecutive acute ischaemic stroke patients undergoing MT during a 1‐year period. Patients received FEES within 5 days of admission regardless of the result of dysphagia screening. We compared baseline demographic and clinical characteristics of patients with and without FEES‐defined dysphagia. We collected 3‐month modified Rankin Scale (mRS) and individual index values of the European Quality of Life 5 Dimensions (EQ‐5D‐iv). Using univariable and multivariable regression analyses we predicted 3‐month outcomes for presence of dysphagia and for FEES‐defined dysphagia severity. Results We included 137 patients with a median age of 74 years, 43.1% were female, median NIHSS was 12 and successful recanalization was achieved in 92.7%. Stroke‐associated pneumonia occurred in 8% of patients. FEES‐defined dysphagia occurred in 81% of patients. Sensitivity of the SSA as a dysphagia screening was 67%. Presence of dysphagia and increasing severity of dysphagia were independently associated with increasing 3‐month mRS score. Increasing dysphagia severity dysphagia was independently associated with lower EQ‐5D‐iv. Interpretation Early FEES‐defined dysphagia occurs in four in every five patients undergoing MT. SSA has a suboptimal dysphagia screening performance. Presence of dysphagia and increasing dysphagia severity predict worse functional outcome and worse health‐related quality‐of‐life.

We consider the problem of multipath entanglement distribution to a pair of nodes in a quantum network consisting of devices with nondeterministic entanglement swapping capabilities. Multipath entanglement distribution enables a network to establish end-to-end entangled links across any number of available paths with preestablished link-level entanglement. Probabilistic entanglement swapping, on the other hand, limits the amount of entanglement that is shared between the nodes; this is especially the case when, due to practical constraints, swaps must be performed in temporal proximity to each other. Limiting our focus to the case where only bipartite entanglement is generated across the network, we cast the problem as an instance of generalized flow maximization between two quantum end nodes wishing to communicate. We propose a mixed-integer quadratically constrained program (MIQCP) to solve this flow problem for networks with arbitrary topology. We then compute the overall network capacity, defined as the maximum number of Einstein–Podolsky–Rosen (EPR) states distributed to users per time unit, by solving the flow problem for all possible network states generated by probabilistic entangled link presence and absence, and subsequently by averaging over all network state capacities. The MIQCP can also be applied to networks with multiplexed links. While our approach for computing the overall network capacity has the undesirable property that the total number of states grows exponentially with link multiplexing capability, it nevertheless yields an exact solution that serves as an upper bound comparison basis for the throughput performance of more easily implementable yet nonoptimal entanglement routing algorithms.

Machine learning has found many applications in network contexts. These include solving optimisation problems and managing network operations. Conversely, networks are essential for facilitating machine learning training and inference, whether performed centrally or in a distributed fashion. To conduct rigorous research in this area, researchers must have a comprehensive understanding of fundamental techniques, specific frameworks, and access to relevant datasets. Additionally, access to training data can serve as a benchmark or a springboard for further investigation. All these techniques are summarized in this article; serving as a primer paper and hopefully providing an efficient start for anybody doing research regarding machine learning for networks or using networks for machine learning.

Quantum protocols commonly require a certain number of quantum resource states to be available simultaneously. An important class of examples is quantum network protocols that require a certain number of entangled pairs. Here, we consider a setting in which a process generates a quantum resource state with some probability $p$ in each time step and stores it in a quantum memory that is subject to time-dependent noise. To maintain sufficient quality for an application, each resource state is discarded from the memory after $w$ time steps. Let $s$ be the number of desired resource states required by a protocol. We characterize the probability distribution $X_{(w,s)}$ of the ages of the quantum resource states, once $s$ states have been generated in a window $w$. Combined with a time-dependent noise model, knowledge of this distribution allows for the calculation of fidelity statistics of the $s$ quantum resources. We also give exact solutions for the first and second moments of the waiting time $\tau _{(w,s)}$ until $s$ resources are produced within a window $w$, which provides information about the rate of the protocol. Since it is difficult to obtain general closed-form expressions for statistical quantities describing the expected waiting time $\mathbb {E}(\tau _{(w,s)})$ and the distribution $X_{(w,s)}$, we present two novel results that aid their computation in certain parameter regimes. The methods presented in this work can be used to analyze and optimize the execution of quantum protocols. Specifically, with an example of a blind quantum computing protocol, we illustrate how they may be used to infer $w$ and $p$ to optimize the rate of successful protocol execution.