bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of machine learning models to prognosticate chronic shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage
Authors: Muscas Giovanni , Matteuzzi Tommaso , Becattini Eleonora , Orlandini Simone , Battista Francesca , Laiso Antonio , Nappini Sergio , Limbucci Nicola , Renieri Leonardo , Carangelo Biagio R. , Mangiafico Salvatore , Della Puppa Alessandro
Published: July 2020

Background

Shunt-dependent hydrocephalus significantly complicates subarachnoid hemorrhage (SAH), and reliable prognosis methods have been sought in recent years to reduce morbidity and costs associated with delayed treatment or neglected onset. Machine learning (ML) defines modern data analysis techniques allowing accurate subject-based risk stratifications. We aimed at developing and testing different ML models to predict shunt-dependent hydrocephalus after aneurysmal SAH.

Methods

We consulted electronic records of patients with aneurysmal SAH treated at our institution between January 2013 and March 2019. We selected variables for the models according to the results of the previous works on this topic. We trained and tested four ML algorithms on three datasets: one containing binary variables, one considering variables associated with shunt-dependency after an explorative analysis, and one including all variables. For each model, we calculated AUROC, specificity, sensitivity, accuracy, PPV, and also, on the validation set, the NPV and the Matthews correlation coefficient (ϕ).

Results

Three hundred eighty-six patients were included. Fifty patients (12.9%) developed shunt-dependency after a mean follow-up of 19.7 (± 12.6) months. Complete information was retrieved for 32 variables, used to train the models. The best models were selected based on the performances on the validation set and were achieved with a distributed random forest model considering 21 variables, with a ϕ = 0.59, AUC = 0.88; sensitivity and specificity of 0.73 (C.I.: 0.39–0.94) and 0.92 (C.I.: 0.84–0.97), respectively; PPV = 0.59 (0.38–0.77); and NPV = 0.96 (0.90–0.98). Accuracy was 0.90 (0.82–0.95).

Conclusions

Machine learning prognostic models allow accurate predictions with a large number of variables and a more subject-oriented prognosis. We identified a single best distributed random forest model, with an excellent prognostic capacity (ϕ = 0.58), which could be especially helpful in identifying low-risk patients for shunt-dependency.
Prevalence of respiratory viruses and antiviral MxA responses in children with febrile urinary tract infection
Authors: Piri Ruut , Ivaska Lauri , Yahya Mohamed , Toivonen Laura , Lempainen Johanna , Kataja Janne , Nuolivirta Kirsi , Tripathi Lav , Waris Matti , Peltola Ville
Published: July 2020

Blood myxovirus resistance protein A (MxA) has broad antiviral activity, and it is a potential biomarker for symptomatic virus infections. Limited data is available of MxA in coinciding viral and bacterial infections. We investigated blood MxA levels in children hospitalized with a febrile urinary tract infection (UTI) with or without simultaneous respiratory virus infection. We conducted a prospective observational study of 43 children hospitalized with febrile UTI. Nasopharyngeal swab samples were collected at admission and tested for 16 respiratory viruses by nucleic acid detection methods. Respiratory symptoms were recorded, and blood MxA levels were determined. The median age of study children was 4 months (interquartile range, 2–14 months). A respiratory virus was detected in 17 (40%) children with febrile UTI. Of the virus-positive children with febrile UTI, 7 (41%) had simultaneous respiratory symptoms. Blood MxA levels were higher in virus-positive children with respiratory symptoms (median, 778 [interquartile range, 535–2538] μg/L) compared to either virus-negative (155 [94–301] μg/L,P < 0.001) or virus-positive (171 [112–331] μg/L,P = 0.006) children without respiratory symptoms at presentation with febrile UTI. MxA differentiated virus-positive children with respiratory symptoms from virus-negative without symptoms by an area under the receiver operating characteristic curve of 0.96. Respiratory viruses were frequently detected in children with febrile UTI. In UTI with simultaneous respiratory symptoms, host antiviral immune response was demonstrated by elevated blood MxA protein levels. MxA protein could be a robust biomarker of symptomatic viral infection in children with febrile UTI.
Workflow optimization for syndromic diarrhea diagnosis using the molecular Seegene Allplex™ GI-Bacteria(I) assay
Authors: Zimmermann Stefan , Horner Susanne , Altwegg Martin , Dalpke Alexander H.
Published: July 2020

Syndromic panel-based molecular testing has been suggested to improve and accelerate microbiological diagnosis. We aimed to analyze workflow improvements when using the multiplex Seegene Allplex™ GI-Bacteria(I) assay as a first-line assay for bacterial diarrhea. Technical assay evaluation was done using spiked stool samples and stored patient samples. After implementation of the assay in the routine clinical workflow, an analysis of 5032 clinical samples analyzed by the Seegene assay and 4173 control samples examined by culture in a similar time period 1 year earlier was performed. Sensitivity of the assay was shown to be between 0.4 and 95.9 genome equivalents/PCR. For 159 positive patient samples with a composite reference of culture and/or a molecular assay, the sensitivity of the assay was 100% forCampylobacter, 92% forSalmonella, 89% forAeromonas, and 83% forShigella. Sensitivity forC. difficiletoxin B detection was 93.9%. The comparison of clinical samples obtained in two 8-month periods showed increased detection rates forAeromonas(2.90%vs. 0.34%),Campylobacterspp. (2.25% vs. 1.34%),Shigellaspp. (0.42% vs. 0.05%) whereas detection ofSalmonellawas slightly decreased (0.46% vs. 0.67%) when using the Seegene assay. An analysis of the time-to-result showed that the median dropped from 52.7 to 26.4 h when using the molecular panel testing. The Seegene Allplex™ GI-Bacteria(I) assay allows accelerated, reliable detection of major gastrointestinal bacteria roughly within 1 day. Workload is reduced, specifically in a low-prevalence setting.
Activity of temocillin against ESBL-, AmpC-, and/or KPC-producing Enterobacterales isolated in Poland
Authors: Kuch Alicja , Zieniuk Bartłomiej , Żabicka Dorota , Van de Velde Sebastien , Literacka Elżbieta , Skoczyńska Anna , Hryniewicz Waleria
Published: July 2020

We evaluated the in vitro effectiveness of temocillin and several commonly used antimicrobials against Enterobacterales bacteria in isolates from Polish patients. We tested 400 isolates: 260 extended-spectrum β-lactamase (ESBL)- and/or ampC β-lactamase (AmpC)-producing isolates; 40 Klebsiella pneumoniae carbapenemase (KPC)-producing isolates; and 100 ESBL-, AmpC-, and KPC-negative isolates. The minimal inhibitory concentrations (MICs) of temocillin and 16 other antimicrobials were determined by reference microdilution. We also determined the activities of fosfomycin and ceftazidime/avibactam in KPC-producing isolates. The antibiotic sensitivities were interpreted according to EUCAST, BSAC, and CLSI criteria. Overall, 91% of the isolates were susceptible to temocillin using the urinary tract infection breakpoint (≤ 32 mg/L), and 61.8% were susceptible using the systemic infection breakpoint (≤ 8 mg/L). Meropenem and imipenem were the most active drugs (MIC50 values of 0.06 and 0.5 mg/L, respectively). Colistin and ertapenem (both MIC50 = 0.12 mg/L) were less active than meropenem or imipenem, but some strains were 77% susceptible to each of them. Among the KPC-producing isolates, 42.5% had MIC values of ≤ 32 mg/L (urinary tract infection breakpoint), but 100% were resistant to temocillin (systemic infection breakpoint). Ceftazidime/avibactam was active against 100% of the KPC-producing isolates, and fosfomycin was active against 40%. The empirical susceptibility rate observed among the urinary isolates suggests that temocillin may be considered as an alternative to carbapenems in the absence of KPC-producing bacteria. With regard to isolates from other sources, temocillin might be useful as a documented therapy agent or an empirical treatment in hospitals with a low prevalence of ESBL/AmpC-producing strains.
Performance and ease of use of a molecular point-of-care test for influenza A/B and RSV in patients presenting to primary care
Authors: Verbakel Jan Y , Matheeussen Veerle , Loens Katherine , Kuijstermans Mandy , Goossens Herman , Ieven Margareta , Butler Christopher C
Published: July 2020

Annual influenza epidemics cause substantial morbidity and mortality, and the majority of patients with influenza-like illness present to primary care. Point-of-care influenza tests could support treatment decisions. It is critical to establish analytic performance of these platforms in real-life patient samples before uptake can be considered. We aimed to assess the analytical performance and ease of use of the cobas® Liat® PCR POCT in detecting influenza A/B and RSV in samples collected from patients with influenza-like illness in primary care. Sensitivity and specificity of the cobas® Liat® POCT are calculated in comparison with a commercial laboratory-based PCR test (Fast-Track Respiratory Pathogens 21 Plus kit (Fast-Track Diagnostics)). Samples with discordant results were analysed additionally by the RespiFinder 2Smart (PathoFinder) using an Extended Gold Standard (EGS). Acceptability was scored on a five-point Likert scale as well as a failure mode analysis of the cobas® Liat® POCT was performed. Nasal and oropharyngeal swabs were obtained from 140 children and nasopharyngeal swabs from 604 adults (744 patients). The cobas® Liat® POCT had a sensitivity and specificity of 100% (95% CI 99–100%) and 98.1% (95%CI 96.3–99%) for influenza A, 100% (95% CI 97.7–100%) and 99.7% (95%CI 98.7–99.9%) for influenza B and 100% (95% CI 87.1–100%) and 99.4% (95%CI 98.6–99.8%) for RSV, respectively. According to trained lab technicians, the cobas® Liat® POCT was considered easy-to-use, with a fast turn-around-time. Cobas® Liat® POCT is a promising decentralised test platform for influenza A/B and RSV in primary care as it provides fairly rapid results with excellent analytic performance. Point-of-care influenza tests could support treatment decisions in primary care. Cobas® Liat® POCT is a promising decentralised test platform for influenza A/B and RSV in primary care as it provides fairly rapid results with excellent analytic performance.
A comparison of GenomEra® GBS PCR and GeneXpert ® GBS PCR assays with culture of GBS performed with and without broth pre-enrichment
Authors: Nielsen S. Y. , Møller J. K. , Khalil M. R.
Published: July 2020

This study was designed to compare the performance of GeneXpert® and GenomEra® group B streptococcus (GBS) PCR assays, held up against standard culture of GBS performed with and without broth pre-enrichment. In Denmark, the strategy for preventing early onset GBS infection (EOGBS) is risk factor based. Three hundred and sixty six women fulfilling one or more of the criteria for presence of risk factors for EOGBS were prospectively included. Rectovaginal swab samples were taken intrapartum and tested bed-site by the GenomEra® and the GeneXpert® GBS PCR assays and cultured at the microbiology laboratory using Granada agar plates with and without prior growth of sampling material in selective enrichment broth. Among 366 participants tested intrapartum, 99 were GBS-positive by culture, 95 by GenomEra, and 95 by GeneXpert. Compared with culture, the GenomEra and the GeneXpert performed with a sensitivity of 91.8% and 91.7% and a specificity of 98.1% and 97.3%, respectively. A combined reference standard was established by defining true positives as either culture-positive samples or culture-negative samples where both the GeneXpert and the GenomEra GBS PCR assays were positive. Using this, the sensitivity increased to 92.2% and the specificity to 99.6% for GenomEra and to 92.0% and 96.8% for GeneXpert. The use of selective broth enrichment found only three additional GBS culture-positive samples. The performance of the two PCR methods examined was very similar and close to the findings by culture, and both PCR assays are thus applicable as rapid intrapartum bed-site tests.
Diagnostic parameters of modified two-tier testing in European patients with early Lyme disease
Authors: Baarsma ME , Schellekens JFP , Meijer BC , Brandenburg AH , Souilljee T. , Hofhuis A , Hovius JW , van Dam AP
Published: July 2020

Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing (STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7–82.9; specificity 96.1%, 95% CI 92.7–98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (p < 0.001), while maintaining comparable specificity (population controlsp = 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.
Long-term cognitive outcome in adult survivors of an early childhood posterior fossa brain tumour
Authors: Wagner Adam P. , Carroll Cliodhna , White Simon R. , Watson Peter , Spoudeas Helen A. , Hawkins Michael M. , Walker David A. , Clare Isabel C. H. , Holland Anthony J. , Ring Howard
Published: July 2020

Purpose

Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT.

Methods

62 adult survivors of a PFT, ascertained from a national register, diagnosed before 5 years of age, and a sibling control, received a single IQ assessment an average of 32 years (range 18–53) after initial diagnosis, using the Weschler Abbreviated Scale of Intelligence. Regression models were fitted to survivor–sibling pair differences on verbal and performance IQ (VIQ and PIQ) scores to investigate whether increasing time between PFT diagnosis and follow-up IQ assessment contributed to survivor–sibling IQ differences.

Results

At follow-up, survivors had, on average, VIQ 15 points and PIQ 19 points lower than their siblings. There was no significant effect of time since diagnosis on survivor–sibling VIQ difference. Survivors who received radiotherapy showed no significant effect of time since diagnosis on survivor–sibling PIQ difference. Survivors who did not receive radiotherapy demonstrated a trend for it to reduce.

Conclusions

VIQ and PIQ deficits persist in adulthood, suggesting the effect of a fixed injury imposing on cognitive development, rather than an ongoing pathological process.

Implications for cancer survivors

The findings will help parents and others supporting survivors of an early life PFT to identify and plan for possible cognitive outcomes, and highlight the importance of early interventions to optimize cognitive function during the developmental period.
The Structural Integrity of Composite Materials and Long-Life Implementation of Composite Structures
Authors: Beaumont Peter W. R.
Published: July 2020

Empirical or semi-empirical design methodologies at the macroscopic scale (structural level) can be supported and justified only by a fundamental understanding at the lower (microscopic) size scale through the physical model. Today structural integrity (SI) is thought as the optimisation of microstructure by controlling processing coupled with intelligent manufacturing of the material: to maximise mechanical performance and ensure reliability of the large scale structure; and to avoid calamity and misfortune. SI analysis provides quantitative input to the formulation of an appropriately balanced response to the problem. This article demonstrates that at the heart of the matter are those mechanisms of crack nucleation and growth that affect the structural integrity of the material: microscopic cracking events that are usually too small to observe and viewed only by microscopy.
Induction: A Logical Analysis
Authors: Saint-Mont Uwe
Published: July 2020

The aim of this contribution is to provide a rather general answer to Hume’s problem. To this end, induction is treated within a straightforward formal paradigm, i.e., several connected levels of abstraction. Within this setting, many concrete models are discussed. On the one hand, models from mathematics, statistics and information science demonstrate how induction might succeed. On the other hand, standard examples from philosophy highlight fundamental difficulties. Thus it transpires that the difference between unbounded and bounded inductive steps is crucial: while unbounded leaps of faith are never justified, there may well be reasonable bounded inductive steps. In this endeavour, the twin concepts of information and probability prove to be indispensable, pinning down the crucial arguments, and, at times, reducing them to calculations. Essentially, a precise study of boundedness settles Goodman’s challenge. Hume’s more profound claim of seemingly inevitable circularity is answered by obviously non-circular hierarchical structures.
Distinct topographic-anatomical patterns in primary and secondary brain tumors and their therapeutic potential
Authors: Akeret Kevin , Staartjes Victor E. , Vasella Flavio , Serra Carlo , Fierstra Jorn , Neidert Marian Christoph , Regli Luca , Krayenbühl Niklaus
Published: July 2020

Purpose

Understanding the topographic-anatomical patterns of brain tumors has the potential to improve our pathophysiological understanding and may allow for anatomical tailoring of surgery and radiotherapy. This study analyzed topographic-anatomical patterns underlying neuroepithelial tumors, primary CNS lymphoma and metastases.

Methods

Any histologically confirmed supra- or infratentorial parenchymal neoplasia of one institution over a 4-year period was included. Using high-resolution magnetic resonance imaging data, a detailed analysis of the topographic-anatomical tumor features was performed. Differences between neuroepithelial tumors, primary central nervous system lymphoma (PCNSL) and metastases were assessed using pairwise comparisons adjusted for multiple testing, upon significance of the omnibus test.

Results

Based on image analysis of 648 patients—419 (65%) neuroepithelial tumors, 28 (5%) PCNSL and 201 (31%) metastases—entity-specific topographic-anatomical patterns were identified. Neuroepithelial tumors showed a radial ventriculo-cortical orientation, inconsistent with the current belief of a growth along white matter tracts, whereas the pattern in PCNSL corresponded to a growth along such. Metastases preferentially affected the cortex and subcortical white matter of large arteries’ terminal supply areas. This study provides a comprehensive anatomical description of the topography of NT, PCNSL and metastases intended to serve as a topographic reference for clinicians and neuroscientists.

Conclusions

The identified distinct anatomical patterns provide evidence for a specific interaction between tumor and anatomical structures, following a pathoclitic concept. Understanding differences in their anatomical behavior has the potential to improve our pathophysiological understanding and to tailor therapy of brain tumors.
Taxing the People, Not Trade: the International Monetary Fund and the Structure of Taxation in Developing Countries
Authors: Reinsberg Bernhard , Stubbs Thomas , Kentikelenis Alexander
Published: July 2020

Strengthening fiscal capacity in low- and middle-income countries is essential for achieving sustainable development. The International Monetary Fund—the world’s premier agent of fiscal policy reform—has taken a front-stage role in this process, promoting a model of tax policy that favors broad-based consumption taxes and discourages trade taxes. This article investigates the links between IMF-mandated tax reforms and the evolution of tax revenues. Using novel measures of tax-related conditionality and disaggregated data on revenues, our analysis shows that IMF interventions are significantly related to changes in tax structure. In particular, IMF programs increase revenues derived from goods and services taxes, but decrease revenues collected from trade taxes. Results for personal and corporate income taxes are inconclusive. These findings have important implications for debates on the role of the IMF in developing countries.
Abnormal Cerebellar Volume in Patients with Remitted Major Depression with Persistent Cognitive Deficits
Authors: Depping Malte S. , Schmitgen Mike M. , Bach Claudia , Listunova Lena , Kienzle Johanna , Kubera Katharina M. , Roesch-Ely Daniela , Wolf R. Christian
Published: July 2020

Cerebellar involvement in major depressive disorder (MDD) has been demonstrated by a growing number of studies, but it is unknown whether cognitive functioning in depressed individuals is related to cerebellar gray matter volume (GMV) abnormalities. Impaired attention and executive dysfunction are characteristic cognitive deficits in MDD, and critically, they often persist despite remission of mood symptoms. In this study, we investigated cerebellar GMV in patients with remitted MDD (rMDD) that showed persistent cognitive impairment. We applied cerebellum-optimized voxel-based morphometry in 37 patients with rMDD and with cognitive deficits, in 12 patients with rMDD and without cognitive deficits, and in 36 healthy controls (HC). Compared with HC, rMDD patients with cognitive deficits had lower GMV in left area VIIA, crus II, and in vermal area VIIB. In patients with rMDD, regression analyses demonstrated significant associations between GMV reductions in both regions and impaired attention and executive dysfunction. Compared with HC, patients without cognitive deficits showed increased GMV in bilateral area VIIIB. This study supports cerebellar contributions to the cognitive dimension of MDD. The data also point towards cerebellar area VII as a potential target for non-invasive brain stimulation to treat cognitive deficits related to MDD.
Public attitude towards cow-calf separation and other common practices of calf rearing in dairy farming—a review
Authors: Placzek M. , Christoph-Schulz I. , Barth K.
Published: July 2020

Public demand for food produced in systems with high animal welfare standards is rising. In terms of animal welfare, the dairy industry has a positive reputation in European countries. However, there are many practices in the dairy industry of which the public is unaware, e.g.,zero-grazing, tethering, dehorning, disposal of male calves, and early cow-calf separation. We focused on the latter and reviewed studies addressing public opinions about dealing with calves in dairy farming. We show that most respondents in studies are unaware or reject these practices. During the last years, more and more attention was paid to cow-calf separation. This practice is mainly rejected because it is considered to be unnatural and associated with stress for the animals. However, there is a lack of scientific surveys that explore the public opinion about how much stress is tolerable in animals that have been allowed to live up to their needs for a period of time. On the other hand, the economic aspects of management practices enabling the animals to express their natural behavior to a greater extent than in the current husbandry systems should be investigated comprehensively. The amount of sales and the willingness to pay a higher price for milk and meat produced in such systems might be the key factors to a wider acceptance of such systems by dairy farmers, who will expect to be compensated for their increased efforts.
Carbonate reservoir characterization: an integrated approach
Authors: Kargarpour Mohammad Ali
Published: July 2020

Estimation of fluid and rock properties of a hydrocarbon reservoir is always a challenging matter; especially, it is true for heterogeneous carbonate reservoirs. Petrophysical logs and laboratory activities are common methods for characterizing a hydrocarbon reservoir. This method in conjunction with geostatistical methods is applied to relatively homogeneous sandstone reservoirs or matrix media of dual-porosity heterogeneous carbonate reservoirs. To estimate properties of fracture system of a dual-media carbonate reservoir, outcrop properties, electrical borehole scans, fractal discrete fracture network and analogy with other reservoirs are common methods. Results which obtained from these methods describe the reservoir in a static way and could be relied on them for very small portion of the reservoir. In this paper, a dynamic procedure for describing reservoir features is proposed in order to enhance the conventional reservoir characterization methods. This method utilizes the reported production data for a specific period of time in conjunction with rock and fluid properties to estimate drainage radius of the well and matrix block height, porosity and width of fracture in the estimated drainage radius. The presented method is elaborated through its application in a real case. By this method, one can generate maps of matrix block size and fracture width and porosity throughout the reservoir. Also, it could be a powerful tool for estimation of effectiveness of acid/hydraulic fracturing activity.
Towards Explanatory Interactive Image Captioning Using Top-Down and Bottom-Up Features, Beam Search and Re-ranking
Authors: Biswas Rajarshi , Barz Michael , Sonntag Daniel
Published: July 2020

Image captioning is a challenging multimodal task. Significant improvements could be obtained by deep learning. Yet, captions generated by humans are still considered better, which makes it an interesting application for interactive machine learning and explainable artificial intelligence methods. In this work, we aim at improving the performance and explainability of the state-of-the-art method Show, Attend and Tell by augmenting their attention mechanism using additional bottom-up features. We compute visual attention on the joint embedding space formed by the union of high-level features and the low-level features obtained from the object specific salient regions of the input image. We embed the content of bounding boxes from a pre-trained Mask R-CNN model. This delivers state-of-the-art performance, while it provides explanatory features. Further, we discuss how interactive model improvement can be realized through re-ranking caption candidates using beam search decoders and explanatory features. We show that interactive re-ranking of beam search candidates has the potential to outperform the state-of-the-art in image captioning.
Modelling the Inundation and Morphology of the Seasonally Flooded Mayas Wetlands in the Dinder National Park-Sudan
Authors: Hassaballah Khalid , Mohamed Yasir , Omer Amgad , Uhlenbrook Stefan
Published: July 2020

Understanding the spatiotemporal dynamics of surface water in varied, remote and inaccessible isolated floodplain lakes is difficult. Seasonal inundation patterns of these isolated lakes can be misestimated in a hydrodynamic model due to the short time of connectivity. The seasonal and annual variability of the Dinder River flow has great impact on what is so called Mayas wetlands, and hence, on the habitats and the ecological status of the Dinder National Park. This variability produces large morphological changes due to sediment transported within the river or from the upper catchment, which affects inflows to Mayas wetlands and floodplain inundation in general. In this paper, we investigated the morphological dimension using a quasi-3D modelling approach to support the management of the valuable Mayas wetlands ecosystems, and in particular, assessment of hydrological and morphological regime of the Dinder River as well as the Musa Maya. Six scenarios were developed and tested. The first three scenarios consider three different hydrologic conditions of average, wet and dry years under the existing system with the constructed connection canal. While the other three scenarios consider the same hydrologic conditions but under the natural system without an artificial connection canal. The modelling helps to understand the effect of human intervention (connection canal) on the Musa Maya. The comparison between the simulated scenarios concludes that the hydrodynamics and sedimentology of the Maya are driven by the two main factors: a) the hydrological variability of Dinder River; and b) deposited sediment plugs in the connection canal.
The distribution of parotid gland neoplasms in a veteran population
Authors: Hussaini Adnan S. , Prasad Navin R. , Paal Edina , Tefera Eshetu A. , Malekzadeh Sonya , Maxwell Jessica H.
Published: July 2020

Objective

Salivary gland tumors account for 6%–8% of head and neck neoplasms with the parotid gland as the most common primary site. Pleomorphic adenomas (PA) are considered the most common benign parotid gland neoplasms, followed by Warthin tumors (WT). The goal of this study was to investigate the distribution of parotid gland neoplasms among a United States veteran population.

Design

Retrospective chart review.

Setting

Washington DC Veterans Affairs Medical Center.

Participants

Veterans who underwent fine needle aspiration (FNA) for a parotid gland mass from 2000 to 2018 were included. Medical records were reviewed for gender, age, tobacco use, surgery date, and pathology results.

Main outcome measures

Changes in the distribution of parotid neoplasms and tobacco use over an 18‐year period.

Results

Of 141 patients with parotid gland masses, 86.5% (n = 122) were benign, 9.9% (n = 14) were malignant, and 3.5% (n = 5) were indeterminate. Of benign tumors, WT accounted for the majority at 51.6%, followed by PA at 40.2%. When stratified by decade (2000–2009 and 2010–2018), the proportion of WT compared to all other benign and malignant neoplasms increased from 31.6% to 53.6%, whereas the proportion of PA decreased from 36.8% to 33.3%. The rate of tobacco use was unchanged at approximately 32.0% among our cohort from 2000 to 2018.

Conclusion

Among our cohort of veteran patients, WT was the most common benign parotid tumor and has increased in incidence over the last two decades despite an unchanged smoking rate.
Resistance is Futile? Ceramic Technology and Social Change in Later Iron Age and Early Roman Britain: Silchester Ware as a Case Study
Authors: Sutton Adam
Published: July 2020

While the basic sequence of innovations that characterise ceramic production in southern Britain during the first centuriesb.c. anda.d. is well-established, our understanding of resistance to these innovations remains in its infancy. Led by the theoretical principles of social constructionism, this paper presents a detailed technological characterisation of Silchester ware, a hand-built ceramic type common in late Iron Age and early Roman Berkshire and northern Hampshire, and a conspicuous example of technological and stylistic anachronism when compared to contemporary wheel-made pottery. Multi-period analyses using radiography, petrography and typology indicate that Silchester ware was not merely a technological ‘hangover’, but a traditional form of material culture with its own role in changing socio-economic structures. Contextualisation of the findings within the local archaeological background further suggests that Silchester ware may have been instrumental in the maintenance of local community and identity at a time when these aspects of social life were under threat. Supplementary material available online (https://doi.org/10.1017/S0068113X20000355) comprises a characterisation of thechaînes opératoiresof Silchester ware and its middle Iron Age antecedents, and a summarised version of the data, interpretations and the original radiographs.
The Myth of the “Civilization State”: Rising Powers and the Cultural Challenge to World Order
Authors: Acharya Amitav
Published: July 2020

“Civilization” is back at the forefront of global policy debates. The leaders of rising powers such as China, India, Turkey, and Russia have stressed their civilizational identity in framing their domestic and foreign policy platforms. An emphasis on civilizational identity is also evident in U.S. president Donald Trump's domestic and foreign policy. Some analysts argue that the twenty-first century might belong to the civilization state, just as the past few centuries were dominated by the nation-state. But is the rise of civilization state inevitable? Will it further undermine the liberal international order and fuel a clash of civilizations, as predicted by the late Samuel Huntington? Or might ideas from East Asian and other non-Western civilizations contribute to greater pluralism in our thinking about world order and the study of international relations?
Nilpotent types and fracture squares in homotopy type theory
Authors: Scoccola Luis
Published: July 2020

We develop the basic theory of nilpotent types and their localizations away from sets of numbers in Homotopy Type Theory. For this, general results about the classifying spaces of fibrations with fiber an Eilenberg–Mac Lane space are proven. We also construct fracture squares for localizations away from sets of numbers. All of our proofs are constructive.
The Fontan outcomes network: first steps towards building a lifespan registry for individuals with Fontan circulation in the United States
Authors: Alsaied Tarek , Allen Kiona Y. , Anderson Jeffrey B. , Anixt Julia S. , Brown David W. , Cetta Frank , Cordina Rachael , D’udekem Yves , Didier Meghan , Ginde Salil , Di Maria Michael V. , Eversole Michelle , Goldberg David , Goldstein Bryan H. , Hoffmann Erin , Kovacs Adrienne H. , Lannon Carole , Lihn Stacey , Lubert Adam M. , Marino Bradley S. , Mullen Emily , Pickles Diane , Rathod Rahul H. , Rychik Jack , Tweddell James S. , Wooton Sharyl , Wright Gail , Younoszai Adel , Glenn Tom , Wilmoth Alicia , Schumacher Kurt
Published: July 2020

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
Analysis of the Man-Made Causes of Shiraz Flash Flood: Iran, 2019
Authors: Heidari Mohammad , Sayfouri Nasrin , Miresmaeeli Seyedeh Samaneh , Nasiri Ali
Published: July 2020

Flood is the most common natural hazard in Iran, which annually affects the environment and human lives. On March 25, 2019 in Shiraz-Iran, following a heavy rainfall, the occurrence of a flash flood caused an extensive number of deaths, injuries, and vehicle demolitions in a short time. Evidence suggests that man-made causes of the incident, including unsustainable urban development and lack of early warning services, have played a more influential role compared with its natural causes. This study has attempted to substantiate that understanding disaster risks, as the first priority of Sendai Framework for Disaster Risk Reduction (SFDRR) 2015-2030, directly impacts the decisions and actions of policymakers, local authorities, and the public. To provide more safety, mitigation, and disaster risk reduction, attention should primarily be paid on making a cultural paradigm shift through providing sufficient training in developing appropriate disaster risk perception in the community at large.
Vitamin D levels are not associated with non-alcoholic fatty liver	disease severity in a Brazilian population
Authors: Dutra Jeniffer Danielle M. , Lisboa Quelson Coelho , Ferolla Silvia Marinho , Carvalho Carolina Martinelli M. L. , Mendes Camila Costa M. , Ferrari Teresa Cristina A. , Couto Cláudia Alves
Published: July 2020

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.
CME: Äthyltoxische Steatohepatitis, der «leise Killer» – vom entzündeten Fett bis zum Multiorganversagen
Authors: Kucsora Natàlia , Becker Björn
Published: July 2020

Zusammenfassung. Das Spektrum der alkoholassoziierten Lebererkrankung (ALD) umfasst die potenziell reversible einfache Verfettung der Leber (AFLD), die äthyltoxische Steatohepatitis (ASH) und die äthyltoxisch bedingte Leberzirrhose. Die alkoholassoziierte Steatohepatitis (ASH), klinisch gekennzeichnet durch Ikterus und Systemic Inflammatory Response Syndrome (SIRS), kann bei fulminantem Verlauf und limitierten Therapieoptionen trotz interdisziplinärer und intensivmedizinischer Behandlung eine Mortalität von bis zu 40 % aufweisen. In hochselektionierten Fällen kann bei Therapieversagen der Standardtherapie mit Kortikosteroiden kombiniert mit N-Acetylcystein eine Lebertransplantation diskutiert werden, deren Langzeitverlauf zum Teil erfreulich ist. Durch den vorliegenden Fall möchten wir bezüglich der Grunderkrankung sensibilisieren, die Prävention hervorheben sowie für die klinische Praxis die wichtigsten Fakten zusammentragen.
Changes to the Madden‐Julian Oscillation in Coupled and Uncoupled Aquaplanet Simulations With 4xCO2
Authors: Bui Hien X. , Maloney Eric D.
Published: July 2020

The impacts of rising carbon dioxide (CO2) concentration and ocean feedbacks on the Madden‐Julian Oscillation (MJO) are investigated with the Community Atmospheric Model Version 5 (CAM5) in an idealized aquaplanet configuration. The climate response associated with quadrupled CO2 concentrations and sea surface temperature (SST) warming are examined in both the uncoupled CAM5 and a version coupled to a slab ocean model. Increasing CO2 concentrations while holding SST fixed produces only small impacts to MJO characteristics, while the SST change resulting from increased CO2 concentrations produces a significant increase in MJO precipitation anomaly amplitude but smaller increase in MJO circulation anomaly amplitude, consistent with previous studies. MJO propagation speed increases in both coupled simulations with quadrupling of CO2 and uncoupled simulations with the same climatological surface temperature warming imposed, although propagation speed is increased more with coupling. While climatological SST changes are identical between coupled and uncoupled runs, other aspects of the basic state such as zonal winds do not change identically. For example, climate warming produces stronger superrotation and weaker mean lower tropospheric easterlies in the coupled run, which contributes to greater increases in MJO eastward propagation speed with warming through its effect on moisture advection. The column process, representing the sum of vertical moist static energy (MSE) advection and radiative heating anomalies, also supports faster eastward propagation with warming in the coupled run. How differing basic states between coupled and uncoupled runs contribute to this behavior is discussed in more detail.
Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model
Authors: Philippou Yiannis , Sjoberg Hanna T. , Murphy Emma , Alyacoubi Said , Jones Keaton I. , Gordon-Weeks Alex N. , Phyu Su , Parkes Eileen E. , Gillies McKenna W. , Lamb Alastair D. , Gileadi Uzi , Cerundolo Vincenzo , Scheiblin David A. , Lockett Stephen J. , Wink David A. , Mills Ian G. , Hamdy Freddie C. , Muschel Ruth J. , Bryant Richard J.
Published: July 2020

Background

Radiotherapy enhances innate and adaptive anti-tumour immunity. It is unclear whether this effect may be harnessed by combining immunotherapy with radiotherapy fractions used to treat prostate cancer. We investigated tumour immune microenvironment responses of pre-clinical prostate cancer models to radiotherapy. Having defined this landscape, we tested whether radiotherapy-induced tumour growth delay could be enhanced with anti-PD-L1.

Methods

Hypofractionated radiotherapy was delivered to TRAMP-C1 and MyC-CaP flank allografts. Tumour growth delay, tumour immune microenvironment flow-cytometry, and immune gene expression were analysed. TRAMP-C1 allografts were then treated with 3 × 5 Gy ± anti-PD-L1.

Results

3 × 5 Gy caused tumour growth delay in TRAMP-C1 and MyC-CaP. Tumour immune microenvironment changes in TRAMP-C1 at 7 days post-radiotherapy included increased tumour-associated macrophages and dendritic cells and upregulation of PD-1/PD-L1, CD8+T-cell, dendritic cell, and regulatory T-cell genes. At tumour regrowth post-3 × 5 Gy the tumour immune microenvironment flow-cytometry was similar to control tumours, however CD8+, natural killer and dendritic cell gene transcripts were reduced. PD-L1 inhibition plus 3 × 5 Gy in TRAMP-C1 did not enhance tumour growth delay versus monotherapy.

Conclusion

3 × 5 Gy hypofractionated radiotherapy can result in tumour growth delay and immune cell changes in allograft prostate cancer models. Adjuncts beyond immunomodulation may be necessary to improve the radiotherapy-induced anti-tumour response.
Impact of mammographic screening and advanced cancer definition on the percentage of advanced-stage cancers in a steady-state breast screening programme in the Netherlands
Authors: de Munck Linda , Siesling Sabine , Fracheboud Jacques , den Heeten Gerard J. , Broeders Mireille J. M. , de Bock Geertruida H.
Published: July 2020

Background

To estimate the percentages of advanced-stage breast cancers (BCs) detected during the course of a steady-state screening programme when using different definitions of advanced BC.

Methods

Data of women aged 49–74 years, diagnosed with BC in 2006–2015, were selected from the Netherlands Cancer Registry and linked to the screening registry. BCs were classified as screen-detected, interval or non-screened. Three definitions of advanced BC were used for comparison: TNM stage (III–IV), NM stage (N+ and/or M+) and T size (invasive tumour ≥15 mm). Analyses were performed assuming a 10% overdiagnosis rate. In sensitivity analyses, this assumption varied from 0 to 30%.

Results

We included 46,734 screen-detected, 17,362 interval and 24,189 non-screened BCs. By TNM stage, 4.9% of screen-detected BCs were advanced, compared with 19.4% and 22.8% of interval and non-screened BCs, respectively (p < 0.001). Applying the other definitions led to higher percentages of advanced BC being detected. Depending on the definition interval, non-screened BCs had a 2–5-times risk of being advanced.

Conclusion

Irrespective of the definition, screen-detected BCs were less frequently in the advanced stage. These findings provide evidence of a stage shift to early detection and support the potential of mammographic screening to reduce treatment-related burdens and the mortality associated with BC.
EPS8 phosphorylation by Src modulates its oncogenic functions
Authors: Shahoumi Linah A. , Khodadadi Hesam , Bensreti Husam , Baban Babak , Yeudall W. Andrew
Published: July 2020

Background

EPS8 is a scaffolding protein that regulates proliferation, actin dynamics and receptor trafficking. Its expression is increased in cancer, enhancing mitogenesis, migration and tumorigenesis. Src phosphorylates EPS8 at four tyrosine residues, although the function is unknown. Here we investigated the pro-oncogenic role of EPS8 tyrosine phosphorylation at Src target sites in HNSCC.

Methods

Plasmids expressing EPS8 Src-mediated phosphorylation site mutants (Y485F, Y525F, Y602F, Y774F and all four combined [FFFF]) were expressed in cells containing a normal endogenous level of EPS8. In addition, cells were treated with dasatinib to inhibit Src activity. EPS8 downstream targets were evaluated by western blotting. Wound closure, proliferation, immunofluorescence and tumorgenicity assays were used to investigate the impact of phenylalanine mutations on EPS8 biological functions.

Results

FOXM1, AURKA, and AURKB were decreased in cells expressing FFFF- and Y602F-EPS8 mutants, while cells harbouring the Y485F-, Y525F- and Y774F-EPS8 mutants showed no differences compared to controls. Consistent with this, dasatinib decreased the expression of EPS8 targets. Moreover, Y602F- and FFFF-EPS8 mutants reduced mitogenesis and motility. Strikingly though, FFFF- or Y602F-EPS8 mutants actually promoted tumorigenicity compared with control cells.

Conclusions

Phosphorylation of EPS8 at Y602 is crucial for signalling to the cell cycle and may provide insight to explain reduced efficacy of dasatinib treatment.
Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability
Authors: Bertan Fabio , Wischhof Lena , Sosulina Liudmila , Mittag Manuel , Dalügge Dennis , Fornarelli Alessandra , Gardoni Fabrizio , Marcello Elena , Di Luca Monica , Fuhrmann Martin , Remy Stefan , Bano Daniele , Nicotera Pierluigi
Published: July 2020

Dendritic spines are postsynaptic domains that shape structural and functional properties of neurons. Upon neuronal activity, Ca2+ transients trigger signaling cascades that determine the plastic remodeling of dendritic spines, which modulate learning and memory. Here, we study in mice the role of the intracellular Ca2+ channel Ryanodine Receptor 2 (RyR2) in synaptic plasticity and memory formation. We demonstrate that loss of RyR2 in pyramidal neurons of the hippocampus impairs maintenance and activity-evoked structural plasticity of dendritic spines during memory acquisition. Furthermore, post-developmental deletion of RyR2 causes loss of excitatory synapses, dendritic sparsification, overcompensatory excitability, network hyperactivity and disruption of spatially tuned place cells. Altogether, our data underpin RyR2 as a link between spine remodeling, circuitry dysfunction and memory acquisition, which closely resemble pathological mechanisms observed in neurodegenerative disorders.