bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidance for Developing Amphibian Population Models for Ecological Risk Assessment
Authors: Awkerman Jill , Raimondo Sandy , Schmolke Amelie , Galic Nika , Rueda-Cediel Pamela , Kapo Katherine , Accolla Chiara , Vaugeois Maxime , Forbes Valery
Published: September 2019

Despite widespread acceptance of the utility of population modeling and advocacy of this approach for a more ecologically relevant perspective, it is not routinely incorporated in ecological risk assessments (ERA). A systematic framework for situation-specific model development is one of the major challenges to broadly adopting population models in ERA. As risk assessors confront the multitude of species and chemicals requiring evaluation, an adaptable stepwise guide for model parameterization would facilitate this process. Additional guidance on interpretation of model output and evaluating uncertainty would further contribute to establishing consensus on good modeling practices. We build on previous work that created a framework and decision guide for developing population models for ERA by focusing on data types, model structure, and extrinsic stressors relevant to anuran amphibians. Anurans have a unique life cycle with varying habitat requirements and high phenotypic plasticity. These species belong to the amphibian class, which is facing global population decline in large part due to anthropogenic stressors, including chemicals. We synthesize information from databases and literature relevant to amphibian risks to identify traits that influence exposure likelihood, inherent sensitivity, population vulnerability, and environmental constraints. We link these concerns with relevant population modeling methods and structure in order to evaluate pesticide effects with appropriate scale and parameterization. A standardized population modeling approach, with additional guidance for anuran ERA, offers an example method for quantifying population risks and evaluating long-term impacts of chemical stressors to populations. Integr Environ Assess Manag 2020;16:223–233. © 2019 SETAC
Loss of interleukin‐10 exacerbates early Type‐1 diabetes‐induced bone loss
Authors: Rios‐Arce Naiomy D. , Dagenais Andrew , Feenstra Derrick , Coughlin Brandon , Kang Ho Jun , Mohr Susanne , McCabe Laura R. , Parameswaran Narayanan
Published: September 2019

Type‐1 diabetes (T1D) increases systemic inflammation, bone loss, and risk for bone fractures. Levels of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) are decreased in T1D, however their role in T1D‐induced osteoporosis is unknown. To address this, diabetes was induced in male IL‐10 knockout (KO) and wild‐type (WT) mice. Analyses of femur and vertebral trabecular bone volume fraction identified bone loss in T1D‐WT mice at 4 and 12 weeks, which in T1D‐IL‐10‐KO mice was further reduced at 4 weeks but not 12 weeks. IL‐10 deficiency also increased the negative effects of T1D on cortical bone. Osteoblast marker osterix was decreased, while osteoclast markers were unchanged, suggesting that IL‐10 promotes anabolic processes. MC3T3‐E1 osteoblasts cultured under high glucose conditions displayed a decrease in osterix which was prevented by addition of IL‐10. Taken together, our results suggest that IL‐10 is important for promoting osteoblast maturation and reducing bone loss during early stages of T1D.
Identification of a six‐gene prognostic signature for oral squamous cell carcinoma
Authors: Wang Jiaying , Wang Yuanyong , Kong Fanzhi , Han Rui , Song Wenbin , Chen Di , Bu Lingxue , Wang Shuangyi , Yue Jin , Ma Lei
Published: September 2019

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies worldwide, and its morbidity and mortality have increased in the near term. Consequently, the purpose of the present study was to identify the notable differentially expressed genes (DEGs) involved in their pathogenesis to obtain new biomarkers or potential therapeutic targets for OSCC. The gene expression profiles of the microarray datasets GSE85195, GSE23558, and GSE10121 were obtained from the Gene Expression Omnibus (GEO) database. After screening the DEGs in each GEO dataset, 249 DEGs in OSCC tissues were obtained. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway enrichment analysis was employed to explore the biological functions and pathways of the above DEGs. A protein–protein interaction network was constructed to obtain a central gene. The corresponding total survival information was analyzed in patients with oral cancer from The Cancer Genome Atlas (TCGA). A total of six candidate genes (CXCL10, OAS2, IFIT1, CCL5, LRRK2, and PLAUR) closely related to the survival rate of patients with oral cancer were identified, and expression verification and overall survival analysis of six genes were performed based on TCGA database. Time‐dependent receiver operating characteristic curve analysis yields predictive accuracy of the patient's overall survival. At the same time, the six genes were further verified by quantitative real‐time polymerase chain reaction using samples obtained from the patients recruited to the present study. In conclusion, the present study identified the prognostic signature of six genes in OSCC for the first time via comprehensive bioinformatics analysis, which could become potential prognostic markers for OCSS and may provide potential therapeutic targets for tumors.
Supervision in genetic counselor training in North America: A systematic review
Authors: Siskind Carly E. , Atzinger Carrie L.
Published: September 2019

Genetic counseling has been a profession for over 40 years, and training programs accredited by the Accreditation Council for Genetic Counseling are required to have students supervised in at least 50 patient‐facing cases prior to graduation. However, there is no standardized information or training for supervisors of genetic counseling students. As a first step toward creating formal and standardized supervision training, we undertook a systematic review of the genetic counseling student supervision literature. A formal systematic review was conducted including establishing a research question with inclusion and exclusion criteria, establishing search terms, searching databases, reading/screening abstracts, examining full texts for inclusion, assessing for quality, and finally extracting data with a standardized form to provide the basis of the review. In all, 151 papers were screened, of which 19 and two erratum were found to meet inclusion criteria and pass quality measures. Main themes from these papers were as follows: Training Model, Competencies, Investigation of Techniques, Difficulties in Supervision, and Barriers. In total, 19 papers provided evidence for the way that supervision is currently being performed and suggestions for what needs further investigation to direct supervision training. Recommendations for genetic counseling student supervision include the following: provide a review of training models to supervisors; provide a copy of the supervision competencies to supervisors; use competencies with lowest self‐efficacy to inform future supervision trainings; and find ways to support genetic counselors in becoming student supervisors.
Prevalence of fatigue among postgraduate trainees in the United States and Japan
Authors: Kato Hirotaka , Burger Alfred P. , Emoto Ken , Sakama Reiko , Uehara Yuki , Segon Ankur , Lin Jenny J.
Published: September 2019

Background

The difference in prevalence of fatigue among postgraduate trainees between the United States and Japan is unknown.

Methods

A cross‐sectional survey using Iowa Fatigue Scale was administered on postgraduate trainees in two internal medicine residency programs in New York and five postgraduate residency programs in Japan.

Results

Of the 393 trainees, 135 (34%) completed the survey. Seventy‐seven (57%) were US trainees. Both fatigue (42% vs 81%) and severe fatigue (4% vs 19%) were more prevalent in Japan (P < .01). US trainees felt more productive during work hours but less fatigued.

Conclusions

Fatigue was more prevalent among postgraduate trainees in Japan.
The impact, cost and cost‐effectiveness of oral pre‐exposure prophylaxis in sub‐Saharan Africa: a scoping review of modelling contributions and way forward
Authors: Case Kelsey K , Gomez Gabriela B , Hallett Timothy B
Published: September 2019

Introduction

Oral pre‐exposure prophylaxis (PrEP) is a new form of HIV prevention being considered for inclusion in national prevention portfolios. Many mathematical modelling studies have been undertaken that speak to the impact, cost and cost‐effectiveness of PrEP programmes. We assess the available evidence from mathematical modelling studies to inform programme planning and policy decision making for PrEP and further research directions.

Methods

We conducted a scoping review of the published modelling literature. Articles published in English which modelled oral PrEP in sub‐Saharan Africa, or non‐specific settings with relevance to generalized HIV epidemic settings, were included. Data were extracted for the strategies of PrEP use modelled, and the impact, cost and cost‐effectiveness of PrEP for each strategy. We define an algorithm to assess the quality and relevance of studies included, summarize the available evidence and identify the current gaps in modelling. Recommendations are generated for future modelling applications and data collection.

Results and Discussion

We reviewed 1924 abstracts and included 44 studies spanning 2007 to 2017. Modelling has reported that PrEP can be a cost‐effective addition to HIV prevention portfolios for some use cases, but also that it would not be cost‐effective to fund PrEP before other prevention interventions are expanded. However, our assessment of the quality of the modelling indicates cost‐effectiveness analyses failed to comply with standards of reporting for economic evaluations and the assessment of relevance highlighted that both key parameters and scenarios are now outdated. Current evidence gaps include modelling to inform service development using updated programmatic information and ex post modelling to evaluate and inform efficient deployment of resources in support of PrEP, especially among key populations, using direct evidence of cost, adherence and uptake patterns.

Conclusions

Updated modelling which more appropriately captures PrEP programme delivery, uses current intervention scenarios, and is parameterized with data from demonstration and implementation projects is needed in support of more conclusive findings and actionable recommendations for programmes and policy. Future analyses should address these issues, aligning with countries to support the needs of programme planners and decision makers for models to more directly inform programme planning and policy.
Separation and indirect ultraviolet detection of ferrous and trivalent iron ions by using ionic liquids in ion chromatography
Authors: Wen Xin‐zhu , Yu Hong , Ma Ya‐jie
Published: September 2019

A method of simultaneous separation and indirect ultraviolet detection of different valence iron ions Fe2+ and Fe3+ by using ionic liquids as mobile phase additives and ultraviolet absorption reagents on a cation exchange column functionalized with carboxylic acid group was developed. The effects of ionic liquids, organic acids, detection wavelength, etc. on separation and detection of Fe2+ and Fe3+ were investigated and the mechanism was discussed. The pyridinium and imidazolium ionic liquids were not only ultraviolet absorption reagents of indirect ultraviolet detection but also effective components for separating Fe2+ and Fe3+. The separation and detection of Fe2+ and Fe3+ can be achieved using 0.5 mmol/L pyridinium ionic liquid−1.2 mmol/L methanesulfonic acid as the mobile phase. The determination of Fe2+ and Fe3+ had a good linear relationship in the concentration range of 1−100 mg/L. The limits of detection of Fe2+ and Fe3+ were 0.12 and 0.09 mg/L, respectively. This method was applied to the actual sample detection in the field of medical analysis. The spiked recoveries were between 97.3 and 99.5%, and the relative standard deviations were less than 0.6%. The method is simple, accurate, and reliable, and is an analytical method with universal and practical value.
Microwave‐Assisted Reversible Coordination‐Mediated Polymerization for Self‐Healing Hybrid Materials: RGO@PDA Simultaneous as Catalyst and Nanocomposites in One‐Pot
Authors: Jiang Xinyan , Wang Wenxiang , Bai Liangjiu , Yang Lixia , Chen Hou , Yang Huawei , Wei Donglei , Cheng Zhenping
Published: September 2019

In this article, polydopamine (PDA) is efficiently adhered on the surface of graphene oxide (GO) by mussel‐inspired chemistry. The obtained reduced GO/PDA (RGO@PDA) nanocomposites are used for catalyzing reversible coordination‐mediated polymerization under microwave radiation. Well‐defined and iodine‐terminated polyacrylonitrile‐co‐poly(n‐butyl acrylate) (PAN‐co‐PnBA) is successfully fabricated by using RGO@PDA nanocomposites as catalysts. Importantly, green and novel strategy of PAN‐co‐PnBA‐type self‐healing nanocomposite materials is further fabricated with RGO@PDA as additive after polymerization as catalyst in one‐pot. As a reinforcement agent, RGO@PDA can also improve the mechanical and self‐healing properties of hybrid materials, which opens up a novel and green methodology for the preparation of self‐healing hybrid materials.
Traveling wave solutions in delayed higher dimensional lattice differential systems with partial monotonicity
Authors: Li Kun , He Yanli
Published: September 2019

In this paper, we consider the existence of traveling wave solutions in delayed higher dimensional lattice differential systems with partial monotonicity. By relaxing the monotonicity of the upper solutions and allowing it greater than positive equilibrium point, we establish the existence of traveling wave solutions by means of Schauder's fixed point theorem. And then, we apply our results to delayed competition‐cooperation systems on higher dimensional lattices.
Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota‐Bile Acid‐FXR Axis in Type 2 Diabetic db/db Mice
Authors: Hui Suocheng , Liu Yang , Chen Mengting , Wang Xiaolan , Lang Hedong , Zhou Min , Yi Long , Mi Mantian
Published: September 2019

Scope

Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear.

Methods and results

Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow‐fed mice, thereby leading to the accumulation of tauro‐β‐muricholic acid (TβMCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP‐induced suppression of enterohepatic FXR‐fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7α‐hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis.

Conclusions

CAP‐induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota‐BA‐enterohepatic FXR axis in db/db mice.
Low‐temperature plasma‐activated medium inhibited invasion and metastasis of melanoma cells via suppressing the Wnt/β‐catenin pathway
Authors: Liu Jin‐Ren , Gao Ling‐Ge , Wu Yue‐Ming , Xu Gui‐Min , Ma Yan , Hao Yue , Shi Xing‐Min , Zhang Guan‐Jun
Published: September 2019

Low‐temperature plasma (LTP) has shown promising and potential applications in the field of biomedicine. The effects of the plasma‐activated medium (PAM) inhibiting tumor cell invasion and metastasis have been verified, but the associated molecular mechanisms are poorly understood. The aim of this study was to identify the anti‐invasion and antimetastasis effects and mechanism induced by PAM on B16 melanoma cells cultured in vitro. For this purpose, an atmospheric pressure plasma jet in helium was applied to generate PAM to treat B16 cells. Cell invasion and migration assays showed that PAM exerted an inhibitory effect on B16 cell invasion and migration in a time‐dependent manner. Then, detection of the invasion‐ and metastasis‐related proteins, including matrix metalloproteinase (MMP)‐2, MMP‐9, CD44, and E‐cadherin, showed that their changes accorded with the invasion and metastasis of the PAM‐treated B16 cells. Furthermore, the Wnt/β‐catenin pathway‐related proteins in PAM‐treated cells were measured, and the pathway was found to be suppressed by PAM. Finally, numerous specific reactive oxygen species (ROS) scavengers were applied to eliminate LTP‐induced ROS in PAM, and it was revealed that H2O2 played a critical role in these processes. These findings demonstrated that PAM exerted anti‐invasion and antimetastasis effects on B16 cells mainly by suppressing the Wnt/β‐catenin pathway, which consequently decreased the expressions of MMP‐9, MMP‐2, and CD44 via H2O2.
Tailoring the Electrochemical Production of H2O2: Strategies for the Rational Design of High‐Performance Electrocatalysts
Authors: Zhang Jiayi , Zhang Haochen , Cheng Mu‐Jeng , Lu Qi
Published: September 2019

The production of H2O2 via the electrochemical oxygen reduction reaction (ORR) presents an attractive decentralized alternative to the current industry‐dominant anthraquinone process. However, in order to achieve viable commercialization of this process, a state‐of‐the‐art electrocatalyst exhibiting high activity, selectivity, and long‐term stability is imperative for industrial applications. Herein, an in‐depth discussion on the current frontiers in electrocatalyst design is provided, emphasizing the influences of electronic and geometric effects, surface structure, and the effects of heteroatom functionalization on the catalytic performance of commonly studied materials (metals, alloys, carbons). The limitations on the performance of the current catalyst materials are also discussed, together with alternative strategies to overcome the impediments. Finally, directions of future research efforts for the discovery of next‐generation ORR electrocatalysts are highlighted.
The utility of infographics in L2 writing classes: A practical strategy to scaffold writing development
Authors: Maamuujav Undarmaa , Krishnan Jenell , Collins Penelope
Published: September 2019

For second language (L2) learners, developing proficiency in academic writing is a cognitively demanding process that requires domain knowledge, in‐depth understanding of rhetoric and genre conventions, and mastery of linguistic principles. Teaching writing to students with diverse cultural and linguistic backgrounds in a way that fosters competence and confidence is equally challenging. However, carefully devised integration of digital tools into L2 writing curriculum can support developing writers. Considering the complexity of writing from students' and instructors' standpoints, this article proposes an integration of infographics into the L2 writing curriculum as a means of (1) supporting the writing development of multilingual students and (2) scaffolding the cognitive demands L2 writers face while composing. It also calls attention to communicative and rhetorical functions of writing. The curricular integration of infographics in second language writing courses is grounded in the process‐based writing approach that involves careful and iterative planning, writing, and revision. Arguing that infographics is an effective digital tool that holds tremendous potential to support both L2 students and instructors in writing intensive classes, the authors explore how infographics can be integrated in process‐based writing curriculum to support the writing development of multilingual students.
The Amsterdam Wrist Rules to reduce the need for radiography after a suspected distal radius fracture: an implementation study
Authors: Mulders Marjolein A. M. , Walenkamp Monique M. J. , Sosef Nico L. , Ouwehand Frank , van Velde Romuald , Goslings Carel , Schep Niels W. L.
Published: September 2019

Purpose

While most patients with wrist trauma are routinely referred for radiography, around 50% of these radiographs show no fracture. To avoid unnecessary radiographs, the Amsterdam Wrist Rules (AWR) have previously been developed and validated. The aim of the current study was to evaluate the effect of the implementation of the AWR at the Emergency Department (ED).

Methods

In a before-and-after comparative prospective cohort study, all consecutive adult patients with acute wrist trauma presenting at the ED of four hospitals were included. Primary outcome was the number of wrist radiographs before and after implementation of the AWR. Secondary outcomes were the number of clinically relevant missed fractures, the overall length of stay in the ED, physician compliance regarding the AWR, and patient satisfaction and experience with the care received at the ED.

Results

A total of 402 patients were included. The absolute reduction in wrist radiographs after implementation was 15% (p < 0.001). One clinically irrelevant fracture was missed. Non-fracture patients without wrist radiography due to the AWR spent 34 min less time in the ED compared with non-fracture patients who had a wrist radiograph (p = 0.015). The physicians adhered to the AWR in 36% of patients. Of all patients who did not receive a radiographic examination of the wrist, 87% were satisfied.

Conclusion

Implementation of the AWR safely reduces the amount of wrist radiographs in selected patients and consequently reducing the length of stay in the ED.
Limited positive effects on jump-landing technique in girls but not in boys after 8 weeks of injury prevention exercise training in youth football
Authors: Lindblom Hanna , Waldén Markus , Carlfjord Siw , Hägglund Martin
Published: September 2019

Purpose

To evaluate changes in jump-landing technique in football-playing boys and girls after 8 weeks of injury prevention training.

Methods

Four boys’ and four girls’ teams (mean age 14.1 ± 0.8 years) were instructed to use either the original Knee Control injury prevention exercise programme (IPEP) or a further developed IPEP, Knee Control + , at every training session for 8 weeks. Baseline and follow-up testing of jump-landing technique included drop vertical jumps (DVJ), assessed subjectively and with two-dimensional movement analysis, and tuck jump assessment (TJA).

Results

Only minor differences in intervention effects were seen between the two IPEPs, and results are therefore presented for both intervention groups combined. At baseline 30% of the boys showed good knee control during the DVJ, normalised knee separation distances of 77–96% (versus hip) and a median of 3 flaws during the TJA. Among girls, 22% showed good knee control, normalised knee separation distances of 67–86% and a median of 4 flaws during the TJA. At follow-up, boys and girls performed significantly more jumps during TJA. No changes in jump-landing technique were seen in boys, whereas girls improved their knee flexion angle at initial contact in the DVJ (mean change + 4.7°, p < 0.001, 95% CI 2.36–6.99, d = 0.7) and their TJA total score (− 1 point, p = 0.045, r = − 0.4).

Conclusion

The study showed small positive effects on jump-landing technique in girls, but not in boys, after 8 weeks of injury prevention training.

Level of evidence

Level II.

Trial registration

Clinical Trials gov identifier: NCT03251404
The relationship among probabilistic, deterministic and potential skills in predicting the ENSO for the past 161 years
Authors: Liu Ting , Tang Youmin , Yang Dejian , Cheng Yanjie , Song Xunshu , Hou Zhaolu , Shen Zheqi , Gao Yanqiu , Wu Yanling , Li Xiaojing , Zhang Banglin
Published: September 2019

Here, we explored in depth the relationship among the deterministic prediction skill, the probabilistic prediction skill and the potential predictability. This was achieved by theoretical analyses and, in particular, by an analysis of long-term ensemble ENSO hindcast over 161 years from 1856 to 2016. First, a nonlinear monotonic relationship between the deterministic prediction skill and the probabilistic prediction skill, derived by theoretical analysis, was examined and validated using the ensemble hindcast. Further, the co-variability between the potential predictability and the deterministic prediction skill was explored in both perfect model assumption and actual model scenario. On these bases, we investigated the relationship between the potential predictability and probabilistic prediction skill from both the practice of ENSO forecast and theoretical perspective. The results of the study indicate that there are nonlinear monotonic relationships among these three kinds of measures. The potential predictability is considered to be a good indicator for the actual prediction skill in terms of both the deterministic measures and the probabilistic framework. The relationships identified here exhibit considerable significant practical sense to conduct predictability researches, which provide an inexpensive and moderate approach for inquiring prediction uncertainties without the requirement of costly ensemble experiments.
Equivalence of Continuous, Local and Infinitesimal Rigidity in Normed Spaces
Authors: Dewar Sean
Published: September 2019

We present a rigorous study of framework rigidity in general finite dimensional normed spaces from the perspective of Lie group actions on smooth manifolds. As an application, we prove an extension of Asimow and Roth’s 1978/1979 result establishing the equivalence of local, continuous and infinitesimal rigidity for regular bar-and-joint frameworks in a d-dimensional Euclidean space. Further, we obtain upper bounds for the dimension of the space of trivial motions for a framework and establish the flexibility of small frameworks in general non-Euclidean normed spaces.
From critical behavior to catastrophic runaways: comparing sheared granular materials with bulk metallic glasses
Authors: Long Alan A. , Denisov Dmitry V. , Schall Peter , Hufnagel Todd C. , Gu Xiaojun , Wright Wendelin J. , Dahmen Karin A.
Published: September 2019

The flow of granular materials and metallic glasses is governed by strongly correlated, avalanche-like deformation. Recent comparisons focused on the scaling regimes of the small avalanches, where strong similarities were found in the two systems. Here, we investigate the regime of large avalanches by computing the temporal profile or “shape” of each one, i.e., the time derivative of the stress-time series during each avalanche. We then compare the experimental statistics and dynamics of these shapes in granular media and bulk metallic glasses. We complement the experiments with a mean-field model that predicts a critical size beyond which avalanches turn into large runaway events. We find that this transition is reflected in a characteristic change of the peak width of the avalanche profile from broad to narrow, and we introduce a new metric for characterizing this dynamic change. The comparison of the two systems points to the same deformation mechanism in both metallic glasses and granular materials.
Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations
Authors: Holleman Marscha S. , Al Maiwenn J. , Zaim Remziye , Groen Harry J. M. , Uyl-de Groot Carin A.
Published: September 2019

Objectives

To compare the cost-effectiveness of first-line gefitinib, erlotinib, afatinib, and osimertinib in patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations.

Methods

A systematic review and network meta-analysis (NMA) were conducted to compare the relative efficacy of gefitinib, erlotinib, afatinib, and osimertinib in EGFR-mutated NSCLC. To assess the cost-effectiveness of these treatments, a Markov model was developed from Dutch societal perspective. The model was based on the clinical studies included in the NMA. Incremental costs per life-year (LY) and per quality-adjusted life-year (QALY) gained were estimated. Deterministic and probabilistic sensitivity analyses (PSA) were conducted.

Results

Total discounted per patient costs for gefitinib, erlotinib, afatinib, and osimertinib were €65,889, €64,035, €69,418, and €131,997, and mean QALYs were 1.36, 1.39, 1.52, and 2.01 per patient, respectively. Erlotinib dominated gefitinib. Afatinib versus erlotinib yielded incremental costs of €27,058/LY and €41,504/QALY gained. Osimertinib resulted in €91,726/LY and €128,343/QALY gained compared to afatinib. PSA showed that gefitinib, erlotinib, afatinib, and osimertinib had 13%, 19%, 43%, and 26% probability to be cost-effective at a threshold of €80,000/QALY. A price reduction of osimertinib of 30% is required for osimertinib to be cost-effective at a threshold of €80,000/QALY.

Conclusions

Osimertinib has a better effectiveness compared to all other TKIs. However, at a Dutch threshold of €80,000/QALY, osimertinib appears not to be cost-effective.
Identification and characterization of the ZRT, IRT-like protein (ZIP) family genes reveal their involvement in growth and kojic acid production in Aspergillus oryzae
Authors: Zhang Zhe , Fan Junxia , Long Chuannan , He Bin , Hu Zhihong , Jiang Chunmiao , Li Yongkai , Ma Long , Wen Jingshang , Zou Xiaojin , Chen Yuan , Ge Zhenxiang , Zeng Bin
Published: September 2019

The ZRT, IRT-like protein (ZIP) family exists in many species and plays an important role in many biological processes, but little is known about ZIP genes in Aspergillus oryzae. Here, 10 ZIP genes in A. oryzae were identified and these were classified into four groups based on phylogenetic analysis. The structures of these AoZip genes were determined, which indicated a great divergence of AoZip members from different groups. Synteny analysis revealed that AoZip7, AoZip8, and AoZip10 are conserved among Aspergillus species. We also found that the promoter regions of AoZip2, AoZip7, AoZip8, and AoZip10 contain multiple conserved response elements. Expression analysis revealed that AoZips exhibited different expression patterns in response to different metal treatments. Moreover, overexpression and RNA-interference (RNAi) of AoZip2 led to a decrease in mycelium growth diameter and inhibited conidia formation. AoZip2 overexpression and RNAi strains showed distinct sensitivity to severely Zn/Mn-depleted stress. In addition, kojic acid production was markedly lower in AoZip2 overexpression and RNAi strains than in the control strains, and the expression of kojA, kojR, and kojT was down-regulated in AoZip2 overexpression and RNAi strains. This study provides new insights into our understanding of ZIP genes and lays a foundation for further investigation of their roles in Aspergillus oryzae.
TRUTH AND FEASIBLE REDUCIBILITY
Authors: ENAYAT ALI , ŁEŁYK MATEUSZ , WCISŁO BARTOSZ
Published: September 2019

Let ${\cal T}$ be any of the three canonical truth theories CT− (compositional truth without extra induction), FS− (Friedman–Sheard truth without extra induction), or KF− (Kripke–Feferman truth without extra induction), where the base theory of ${\cal T}$ is PA (Peano arithmetic). We establish the following theorem, which implies that ${\cal T}$ has no more than polynomial speed-up over PA.

Theorem.${\cal T}$is feasibly reducible to PA, in the sense that there is a polynomial time computable function f such that for every${\cal T}$-proof π of an arithmetical sentence ϕ, f (π) is a PA-proof of ϕ.
THEDĒMOSINDĒMOKRATIA
Authors: Cammack Daniela
Published: September 2019

The meaning ofdēmokratiais widely agreed: ‘rule by the people’ (less often ‘people-power’), wheredēmos, ‘people’, implies ‘entire citizen body’, synonymous withpolis, ‘city-state’, or πάντες πολίται, ‘all citizens’.Dēmos, on this understanding, comprised rich and poor, leaders and followers, mass and elite alike. As such,dēmokratiais interpreted as constituting a sharp rupture from previous political regimes. Rule by one man or by a few had meant the domination of one part of the community over the rest, butdēmokratia, it is said, implied self-rule, and with it the dissolution of the very distinction between ruler and ruled. Its governing principle was the formal political equality of all citizens. In the words of W.G. Forrest, between 750 and 450b.c.there had developed ‘the idea of individual human autonomy … the idea that all members of a political society are free and equal, that everyone had the right to an equal say in determining the structure and the activities of his society’.
Surrogate rearing a keystone species to enhance population and ecosystem restoration
Authors: Mayer Karl A. , Tinker M. Tim , Nicholson Teri E. , Murray Michael J. , Johnson Andrew B. , Staedler Michelle M. , Fujii Jessica A. , Van Houtan Kyle S.
Published: September 2019

Translocation and rehabilitation programmes are critical tools for wildlife conservation. These methods achieve greater impact when integrated in a combined strategy for enhancing population or ecosystem restoration. During 2002–2016 we reared 37 orphaned southern sea otter Enhydra lutris nereis pups, using captive sea otters as surrogate mothers, then released them into a degraded coastal estuary. As a keystone species, observed increases in the local sea otter population unsurprisingly brought many ecosystem benefits. The role that surrogate-reared otters played in this success story, however, remained uncertain. To resolve this, we developed an individual-based model of the local population using surveyed individual fates (survival and reproduction) of surrogate-reared and wild-captured otters, and modelled estimates of immigration. Estimates derived from a decade of population monitoring indicated that surrogate-reared and wild sea otters had similar reproductive and survival rates. This was true for males and females, across all ages (1–13 years) and locations evaluated. The model simulations indicated that reconstructed counts of the wild population are best explained by surrogate-reared otters combined with low levels of unassisted immigration. In addition, the model shows that 55% of observed population growth over this period is attributable to surrogate-reared otters and their wild progeny. Together, our results indicate that the integration of surrogacy methods and reintroduction of juvenile sea otters helped establish a biologically successful population and restore a once-impaired ecosystem.
Greek Declamation Beyond Philostratus’ Second Sophistic
Authors: Guast William
Published: September 2019

This article examines the surviving Greek declamations of the first to third century AD. They are found to be at odds with Philostratus’ familiar picture of the genre in respect of their brevity and stylistic simplicity. Explanations in terms of forgery/misattribution, textual adulteration of some form or the youth of the declaimers at the time of composition are rejected, and it is concluded rather that Philostratus’ picture of the genre is significantly distorted. Specifically, the Vitae sophistarum (1) omit declamations composed for didactic ends in favour of show declamations and (2) even among show declamations focus almost exclusively on the more florid end of the stylistic spectrum.
Social networking sites and the experience of older adult users: a systematic review
Authors: Newman Loveday , Stoner Charlotte , Spector Aimee
Published: September 2019

This study aimed to systematically review the use of social networking sites (SNSs) from an older adult perspective (all papers had an average sample age of 65+ and samples ranged in age from 50 to 98). Characteristics of older adult SNS users, incentives and disincentives for use, and the relationship between SNS use, wellbeing and cognitive function were explored. From a systematic search, 21 papers met inclusion criteria and were subjected to a quality review. Paper quality was often low or medium, as rated by a standard quality assessment framework. Results indicated that older adult SNS users were more likely to have particular characteristics, including being female and younger. The main incentive for use was to maintain contact with family and friends. Disincentives included privacy concerns and lack of perceived usefulness. The relationship between SNS use, wellbeing and cognitive function was inconclusive. SNS use is a multi-dimensional phenomenon that needs to be understood in the context of broader communication practices, individuals’ social relationships, and individual preferences and characteristics.
Law of Nations Theory and the Native Sovereignty Debates in Colonial India
Authors: Leonard Zak
Published: September 2019

Beginning in the 1840s, high-ranking officials within the East India Company began a concerted effort to confiscate and annex princely states, citing misrule or a default of blood heirs. In response, metropolitan reformers and their Indian allies orchestrated a sustained legalistic defense of native sovereignty in the public sphere and emerged as vocal opponents of colonial expansionism. Adapting concepts put forth by both law of nations theorists and contemporary jurists, they sought to preserve longstanding treaties and defend the princes' exercise of internal sovereignty. The colonial government's failure to adequately define the basis of its modern “paramountcy” invited such creative maneuvering. Reformist opposition to the annexation of Awadh, the dispossession of the Nawab of the Carnatic, and the confiscation of Mysore demonstrates that international law did not simply function as a Eurocentric tool of subordination, but could also provide a bulwark against colonial depredations.
Twenty-five years of information extraction
Authors: Grishman Ralph
Published: September 2019

Information extraction is the process of converting unstructured text into a structured data base containing selected information from the text. It is an essential step in making the information content of the text usable for further processing. In this paper, we describe how information extraction has changed over the past 25 years, moving from hand-coded rules to neural networks, with a few stops on the way. We connect these changes to research advances in NLP and to the evaluations organized by the US Government.
Exploring food preparation practices in families with and without school-aged childhood cancer survivors
Authors: Raber Margaret , Crawford Karla , Baranowski Tom , Sharma Shreela V , Schick Vanessa , Markham Christine , Roth Michael , Chandra Joya
Published: September 2019

Objective:

Survival rates for paediatric cancers have increased dramatically since the 1970s, but childhood cancer survivors (CCS) are at increased risk for several chronic diseases throughout life. Nutrition interventions promoting healthy family meals may support wellness for survivors, but little research has explored CCS family food preparation habits. The goal of the present study was to describe and compare food preparation practices of CCS and non-CCS families.

Design:

Observational.

Setting:

Typical evening meal preparation events were observed and recorded in participant homes. Recordings and notes were analysed using the Healthy Cooking Index (HCI), a measure of nutrition-optimizing food preparation practices relevant to survivor wellness. Demographics, BMI and nutrient composition of prepared meals were also collected.

Participants:

Forty parents with a CCS or non-CCS child aged 5–17 years were recruited.

Results:

There were no major differences between the CCS and non-CCS families with regard to summative HCI score or specific food preparation behaviours. Meals prepared by CCS and non-CCS families had similar nutrient compositions.

Conclusions:

The study revealed areas for practical nutrition intervention in CCS and non-CCS families. Future studies should consider adopting and tailoring nutrition intervention methods that have been successful in non-CCS communities.
Resource Analysis driven by (Conditional) Termination Proofs
Authors: ALBERT ELVIRA , BOFILL MIQUEL , BORRALLERAS CRISTINA , MARTIN-MARTIN ENRIQUE , RUBIO ALBERT
Published: September 2019

When programs feature a complex control flow, existing techniques for resource analysis produce cost relation systems (CRS) whose cost functions retain the complex flow of the program and, consequently, might not be solvable into closed-form upper bounds. This paper presents a novel approach to resource analysis that is driven by the result of a termination analysis. The fundamental idea is that the termination proof encapsulates the flows of the program which are relevant for the cost computation so that, by driving the generation of the CRS using the termination proof, we produce a linearly-bounded CRS (LB-CRS). A LB-CRS is composed of cost functions that are guaranteed to be locally bounded by linear ranking functions and thus greatly simplify the process of CRS solving. We have built a new resource analysis tool, named MaxCore, that is guided by the VeryMax termination analyzer and uses CoFloCo and PUBS as CRS solvers. Our experimental results on the set of benchmarks from the Complexity and Termination Competition 2019 for C Integer programs show that MaxCore outperforms all other resource analysis tools.
Better Paracoherent Answer Sets with Less Resources
Authors: AMENDOLA GIOVANNI , DODARO CARMINE , RICCA FRANCESCO
Published: September 2019

Answer Set Programming (ASP) is a well-established formalism for logic programming. Problem solving in ASP requires to write an ASP program whose answers sets correspond to solutions. Albeit the non-existence of answer sets for some ASP programs can be considered as a modeling feature, it turns out to be a weakness in many other cases, and especially for query answering. Paracoherent answer set semantics extend the classical semantics of ASP to draw meaningful conclusions also from incoherent programs, with the result of increasing the range of applications of ASP. State of the art implementations of paracoherent ASP adopt the semi-equilibrium semantics, but cannot be lifted straightforwardly to compute efficiently the (better) split semi-equilibrium semantics that discards undesirable semi-equilibrium models. In this paper an efficient evaluation technique for computing a split semi-equilibrium model is presented. An experiment on hard benchmarks shows that better paracoherent answer sets can be computed consuming less computational resources than existing methods.
Anti-unification in Constraint Logic Programming
Authors: YERNAUX GONZAGUE , VANHOOF WIM
Published: September 2019

Anti-unification refers to the process of generalizing two (or more) goals into a single, more general, goal that captures some of the structure that is common to all initial goals. In general one is typically interested in computing what is often called a most specific generalization, that is a generalization that captures a maximal amount of shared structure. In this work we address the problem of anti-unification in CLP, where goals can be seen as unordered sets of atoms and/or constraints. We show that while the concept of a most specific generalization can easily be defined in this context, computing it becomes an NP-complete problem. We subsequently introduce a generalization algorithm that computes a well-defined abstraction whose computation can be bound to a polynomial execution time. Initial experiments show that even a naive implementation of our algorithm produces acceptable generalizations in an efficient way.
A Distributed Approach to LARS Stream Reasoning (System paper)
Authors: EITER THOMAS , OGRIS PAUL , SCHEKOTIHIN KONSTANTIN
Published: September 2019

Stream reasoning systems are designed for complex decision-making from possibly infinite, dynamic streams of data. Modern approaches to stream reasoning are usually performing their computations using stand-alone solvers, which incrementally update their internal state and return results as the new portions of data streams are pushed. However, the performance of such approaches degrades quickly as the rates of the input data and the complexity of decision problems are growing. This problem was already recognized in the area of stream processing, where systems became distributed in order to allocate vast computing resources provided by clouds. In this paper we propose a distributed approach to stream reasoning that can efficiently split computations among different solvers communicating their results over data streams. Moreover, in order to increase the throughput of the distributed system, we suggest an interval-based semantics for the LARS language, which enables significant reductions of network traffic. Performed evaluations indicate that the distributed stream reasoning significantly outperforms existing stand-alone LARS solvers when the complexity of decision problems and the rate of incoming data are increasing.
Control-Flow Refinement by Partial Evaluation, and its Application to Termination and Cost Analysis
Authors: DOMÉNECH JESÚS J. , GALLAGHER JOHN P. , GENAIM SAMIR
Published: September 2019

Control-flow refinement refers to program transformations whose purpose is to make implicit control-flow explicit, and is used in the context of program analysis to increase precision. Several techniques have been suggested for different programming models, typically tailored to improving precision for a particular analysis. In this paper we explore the use of partial evaluation of Horn clauses as a general-purpose technique for control-flow refinement for integer transitions systems. These are control-flow graphs where edges are annotated with linear constraints describing transitions between corresponding nodes, and they are used in many program analysis tools. Using partial evaluation for control-flow refinement has the clear advantage over other approaches in that soundness follows from the general properties of partial evaluation; in particular, properties such as termination and complexity are preserved. We use a partial evaluation algorithm incorporating property-based abstraction, and show how the right choice of properties allows us to prove termination and to infer complexity of challenging programs that cannot be handled by state-of-the-art tools. We report on the integration of the technique in a termination analyzer, and its use as a preprocessing step for several cost analyzers.
A Syntactic Operator for Forgetting that Satisfies Strong Persistence
Authors: BERTHOLD MATTI , GONÇALVES RICARDO , KNORR MATTHIAS , LEITE JOÃO
Published: September 2019

Whereas the operation of forgetting has recently seen a considerable amount of attention in the context of Answer Set Programming (ASP), most of it has focused on theoretical aspects, leaving the practical issues largely untouched. Recent studies include results about what sets of properties operators should satisfy, as well as the abstract characterization of several operators and their theoretical limits. However, no concrete operators have been investigated.

In this paper, we address this issue by presenting the first concrete operator that satisfies strong persistence – a property that seems to best capture the essence of forgetting in the context of ASP – whenever this is possible, and many other important properties. The operator is syntactic, limiting the computation of the forgetting result to manipulating the rules in which the atoms to be forgotten occur, naturally yielding a forgetting result that is close to the original program.