bluuebunny/crossref_metadata_2025 huggingface dataset:
Ein treuer Freund und guter Verbündeter
Authors: Fuchs Irmgard
Published: April 2019

Am Anfang der europäischen Tierepik steht der Roman de Renart, eine Sammlung altfranzösischer Erzählungen. Ausgehend von ihm verbreitet sich der Erzählstoff in einer deutschen und einer niederländischen Erzähltradition über Europa. Auch wenn die Fassungen auf derselben stofflichen Vorlage basieren, zeigen bereits die je unterschiedlichen Erzählstrukturen, dass die Dichter beim Wiedererzählen jeweils eigene Akzente gesetzt haben. Dies hat auch Folgen für den Umgang mit Themen wie 'Treue', einem Schlüsselbegriff der höfischen Kultur. Der vorliegende Beitrag untersucht Le Roman de Renart, Van den vos Reynaerde und Reinhart Fuchs anhand einer ihnen gemeinsamen Szene, nämlich der ersten Vorladung des Fuchses durch den Bären. Nach Erläuterungen zum Bedeutungsspektrum von 'Treue' werden die drei Fassungen miteinander verglichen. Dabei ist zu fragen, wie der niederländische Dichter und der deutsche Dichter den gegebenen Erzählstoff umgestaltet haben und wie in ihren Erzählungen 'Treue' auf narrativer und semantischer Ebene präsentiert wird.
A selective survey of visual representations of Reynardian Literature and fox lore in the last fifty years
Authors: Varty Kenneth , Wackers Paul
Published: April 2019

This article offers a survey of fifty years research into Reynardian iconography. It analyses secondary and primary sources: it discusses a number of book length studies, it shows trends in articles, makes suggestions for further research, describes the properties of and the main research on the major illustration cycles of Reynardian literature and ends with an annotated bibliography.
Somatic autophagy of axonal mitochondria in ischemic neurons
Authors: Zheng Yanrong , Zhang Xiangnan , Wu Xiaoli , Jiang Lei , Ahsan Anil , Ma Shijia , Xiao Ziyu , Han Feng , Qin Zheng-Hong , Hu Weiwei , Chen Zhong
Published: April 2019

Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in Atg7fl/fl;nes-Cre neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.
Report on the comparison of the calibration of noble metal thermocouples from 419 ºC up to 1100 ºC (EURAMET.T-S5)
Authors: Campo Dolores del , García Izquierdo Carmen , Petrusova Olgica , Soto Juan Carlos
Published: April 2019

An International Comparison on the calibration of noble metal thermocouples from 419 °C up to 1100 °C has been carried out among the National Metrology Institutes (NMIs) of Spain, FYR Macedonia and Chile. Measurements were performed from March 2016 to June 2017. One type R thermocouple circulated between the participants that was calibrated by using fixed points or by comparison, depending of the capabilities of the laboratories. The Centro Español de Metrología (Spanish NMI), CEM, acted as the pilot laboratory providing the reference value of the comparison.

The thermocouple shown an acceptable behavior throughout the comparison, with no critical deterioration of its homogeneity and a maximum drift lower than 2 μV in the worst case. The results of the comparison were quite satisfactory. The three institutes are compatible with a coverage factor k= 2 in all the calibration points and in the case of aluminum and zinc they are even compatible for a coverage factor k = 1.

This report presents the results of this comparison and provides detailed information of the measurements performed by the participating laboratories.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Thermodynamic Stability, Half-Metallic and Optical Properties of Sc2CoSi [001] Film: a DFT Study
Authors: Amiri Maliheh , Akbari Hossein , Nedaee-shakarab Bashir , Boochani Arash , Aminian Amin , Zangeneh Yousof , Naderi Sirvan
Published: April 2019

The electronic and optical characteristics of the Sc
2
CoSi Heusler with L21 structure and also the surface effect on electronic and optical properties, and the films thermodynamic stability of the [001] direction in four cases including: Sc-Sc, Sc-Co, Sc-Si and Co-Si terminations are studied using the first principles calculations (FPLAPW) within the framework of the density functional theory (DFT). The band structure calculations represent the ferromagnetic half-metallic properties with 100% spin polarization and 0.54 eV indirect gap in spin down for Sc
2
CoSi bulk with optimized lattice parameters of 6.25 Å. The total magnetic moment obtained for this compound is −1.0 μB, which is in accordance with Slater-Pauling rule. The half-metallic (HM) behavior by 100% spin polarization at Fermi level is occurred in the Sc-Si termination with a 0.32 eV gap in down spin. The optical responses have been calculated for the bulk and Sc-Si termination by a red shift in these parameters and the metallic treatments have been increased. According to the thermodynamic phase diagrams, it is shown the Sc-Si and Sc-Sc terminations are more stable than other terminations.
Cross-sectional Association Between Blood Pressure Status and Atrial Fibrillation in an Elderly Chinese Population
Authors: Chen Yi , Huang Qi-Fang , Sheng Chang-Sheng , Lei Lei , Xu Shao-Kun , Zhang Wei , Shao Shuai , Wang Dian , Cheng Yi-Bang , Wang Ying , Guo Qian-Hui , Zhang Dong-Yan , Li Yan , Li Yong , Freedman S Ben , Wang Ji-Guang
Published: April 2019

OBJECTIVE

Atrial fibrillation (AF) and hypertension are prevalent chronic disease conditions in the elderly population. In the present cross-sectional study, we investigated the association between blood pressure (BP) and AF in an elderly Chinese population.

METHOD

Our elderly (≥65 years) subjects were residents recruited from 6 communities in Shanghai from 2006 to 2017. Atrial fibrillation was systematically screened by rest 12-lead electrocardiogram (ECG) or by a handheld single-lead ECG. BP status was defined according to the European hypertension guidelines as optimal, normal, or high-normal BP, and stage 1, 2, or 3 hypertension.

RESULT

In the 6,966 participants (women 56.0%, mean age: 72.3 years), the prevalence of AF was 3.3%, and the prevalence of hypertension was 58.7% (83.7% treated). In all participants, the association with prevalent AF was negative for systolic BP (odds ratio [OR] per 10-mm Hg increase 0.79, 95% confidence interval [CI]: 0.71–0.88, P < 0.0001) but positive for diastolic BP (OR per 5-mm Hg increase 1.11, 95% CI: 1.02–1.22, P = 0.02). In untreated participants (n = 3,544), the association with prevalent AF was U-shaped for both systolic and diastolic BP, with the nadir at high-normal BP and a significantly higher risk of prevalent AF in optimal systolic BP (OR: 3.11, 95% CI: 1.65–5.85, P = 0.004) and stage 2 or 3 diastolic hypertension relative to the nadir (OR: 8.04, 95% CI: 2.28–28.3, P = 0.001).

CONCLUSION

In the elderly population, BP shows a complicated relationship with prevalent AF, with high-normal BP at the lowest risk and optimal systolic BP and stage 2 or 3 diastolic hypertension at increased risks.
MethylSeqDesign: a framework for Methyl-Seq genome-wide power calculation and study design issues
Authors: Liu Peng , Lin Chien-Wei , Park Yongseok , Tseng George
Published: April 2019

Bisulfite DNA methylation sequencing (Methyl-Seq) becomes one of the most important technologies to study methylation level difference at a genome-wide scale. Due to the complexity and large scale of methyl-Seq data, power calculation and study design method have not been developed. Here, we propose a “MethylSeqDesign” framework for power calculation and study design of Methyl-Seq experiments by utilizing information from pilot data. Differential methylation analysis is based on a beta-binomial model. Power calculation is achieved using mixture model fitting of p-values from pilot data and a parametric bootstrap procedure. To circumvent the issue of existing tens of millions of methylation sites, we focus on the inference of pre-specified targeted regions. The performance of the method was evaluated with simulations. Two real examples are analyzed to illustrate our method. An R package “MethylSeqDesign” to implement this method is publicly available.
The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations
Authors: Rodríguez Cruz Pedro M. , Cossins Judith , de Paula Estephan Eduardo , Munell Francina , Selby Kathryn , Hirano Michio , Maroofin Reza , Mehrjardi Mohammad Yahya Vahidi , Chow Gabriel , Carr Aisling , Manzur Adnan , Robb Stephanie , Munot Pinki , Wei Liu Wei , Banka Siddharth , Fraser Harry , De Goede Christian , Zanoteli Edmar , Conti Reed Umbertina , Sage Abigail , Gratacos Margarida , Macaya Alfons , Dusl Marina , Senderek Jan , Töpf Ana , Hofer Monika , Knight Ravi , Ramdas Sithara , Jayawant Sandeep , Lochmüller Hans , Palace Jacqueline , Beeson David
Published: April 2019

Next generation sequencing techniques were recently used to show mutations in COL13A1 cause synaptic basal lamina-associated congenital myasthenic syndrome type 19. Animal studies showed COL13A1, a synaptic extracellular-matrix protein, is involved in the formation and maintenance of the neuromuscular synapse that appears independent of the Agrin-LRP4-MuSK-DOK7 acetylcholine receptor clustering pathway. Here, we report the phenotypic spectrum of 16 patients from 11 kinships harbouring homozygous or heteroallelic mutations in COL13A1. Clinical presentation was mostly at birth with hypotonia and breathing and feeding difficulties often requiring ventilation and artificial feeding. Respiratory crisis related to recurrent apnoeas, sometimes triggered by chest infections, were common early in life but resolved over time. The predominant pattern of muscle weakness included bilateral ptosis (non-fatigable in adulthood), myopathic facies and marked axial weakness, especially of neck flexion, while limb muscles were less involved. Other features included facial dysmorphism, skeletal abnormalities and mild learning difficulties. All patients tested had results consistent with abnormal neuromuscular transmission. Muscle biopsies were within normal limits or showed non-specific changes. Muscle MRI and serum creatine kinase levels were normal. In keeping with COL13A1 mutations affecting both synaptic structure and presynaptic function, treatment with 3,4-diaminopyridine and salbutamol resulted in motor and respiratory function improvement. In non-treated cases, disease severity and muscle strength improved gradually over time and several adults recovered normal muscle strength in the limbs. In summary, patients with COL13A1 mutations present mostly with severe early-onset myasthenic syndrome with feeding and breathing difficulties. Axial weakness is greater than limb weakness. Disease course improves gradually over time, which could be consistent with the less prominent role of COL13A1 once the neuromuscular junction is mature. This report emphasizes the role of collagens at the human muscle endplate and should facilitate the recognition of this disorder, which can benefit from pharmacological treatment.
Integration of transthoracic focused cardiac ultrasound in the diagnostic algorithm for suspected acute aortic syndromes
Authors: Nazerian Peiman , Mueller Christian , Vanni Simone , Soeiro Alexandre de Matos , Leidel Bernd A , Cerini Gabriele , Lupia Enrico , Palazzo Andrea , Grifoni Stefano , Morello Fulvio
Published: April 2019

Aims

The diagnosis of acute aortic syndromes (AASs) is challenging and requires integrated strategies. Transthoracic focused cardiac ultrasound (FoCUS) is endorsed by guidelines as a first-line/triage tool allowing rapid bedside assessment of the aorta. However, the performance of FoCUS in the European Society of Cardiology-recommended workup of AASs awaits validation.

Methods and results

This was a prespecified subanalysis of the ADvISED multicentre prospective study. Patients with suspected AAS underwent FoCUS for detection of direct/indirect signs of AAS. Clinical probability assessment was performed with the aortic dissection detection risk score (ADD-RS). Case adjudication was based on advanced imaging, surgery, autopsy, or 14-day follow-up. An AAS was diagnosed in 146 (17.4%) of 839 patients. Presence of direct FoCUS signs had a sensitivity and specificity of 45.2% [95% confidence interval (CI) 37–53.6%] and 97.4% (95% CI 95.9–98.4%), while presence of any FoCUS sign had a sensitivity and specificity of 89% (95% CI 82.8–93.6%) and 74.5% (95% CI 71–77.7%) for AAS. The additive value of FoCUS was most evident within low clinical probability (ADD-RS ≤1). Herein, direct FoCUS signs were identified in 40 (4.8%) patients (P < 0.001), including 29 with AAS. ADD-RS ≤1 plus negative FoCUS for AAS rule-out had a sensitivity of 93.8% (95% CI 88.6–97.1%) and a failure rate of 1.9% (95% CI 0.9–3.6%). Addition of negative D-dimer led to a failure rate of 0% (95% CI 0–1.2%).

Conclusion

FoCUS has additive value in the workup of AASs. Direct FoCUS signs can rapidly identify patients requiring advanced imaging despite low clinical probability. In integrated bundles, negative FoCUS is useful for rule-out of AASs.
Non-paroxysmal atrial fibrillation mapping: characterization of the electrophysiological substrate using a novel integrated mapping technique
Authors: Ciconte Giuseppe , Vicedomini Gabriele , Li Wenwen , Mangual Jan O , McSpadden Luke , Ryu Kyungmoo , Saviano Massimo , Vitale Raffaele , Conti Manuel , Ćalović Žarko , Santinelli Vincenzo , Pappone Carlo
Published: April 2019

Aims

Clinical outcomes after radiofrequency catheter ablation (RFCA) remain suboptimal in the treatment of non-paroxysmal atrial fibrillation (AF). Electrophysiological mapping may improve understanding of the underlying mechanisms. To describe the arrhythmia substrate in patients with persistent (Pers) and long-standing persistent (LSPers) AF, undergoing RFCA, using an integrated mechanism mapping technique.

Methods and results

Patients underwent high-density electroanatomical mapping before and after catheter ablation. Integrated maps characterized electrogram (EGM) cycle length (CL) in regions with repetitive–regular (RR) activations, stable wavefront propagation, fragmentation, and peak-to-peak bipolar voltage. Among 83 patients (72% male, 60 ± 11 years old), RR activations were identified in 376 regions (mean CL 180 ± 31 ms). PersAF patients (n = 43) showed more RR sites per patient (5.3 ± 2.4 vs. 3.7 ± 2.1, P = 0.002) with faster CL (166 ± 29 vs. 190 ± 29 ms; P < 0.001) and smaller surface area of fragmented EGMs (15 ± 14% vs. 27 ± 17%, P < 0.001) compared with LSPersAF. The post-ablation map in 50 patients remaining in AF, documented reduction of the RR activities per patient (1.5 ± 0.7 vs. 3.7 ± 1.4, P < 0.001) and area of fragmentation (22 ± 17% vs. 8 ± 9%, P < 0.001). Atrial fibrillation termination during ablation occurred at RR sites (0.48 ± 0.24 mV; 170.5 ± 20.2 ms CL) in 31/33 patients (94%). At the latest follow-up, arrhythmia freedom was higher among patients receiving ablation >75% of RR sites (Q4 82.6%, Q3 63.1%, Q2 35.1%, and Q1 0%; P < 0.001).

Conclusion

The integrated mapping technique allowed characterization of multiple arrhythmic substrates in non-paroxysmal AF patients. This technique might serve as tool for a substrate-targeted ablation approach.
Organization and regulation of cyanobacterial nif gene clusters: implications for nitrogenase expression in plant cells
Authors: Thiel Teresa
Published: April 2019

For over 50 years scientists have considered the possibility of engineering a plant with nitrogen fixation capability, freeing farmers from their dependence on nitrogen fertilizers. With the development of the tools of synthetic biology, more progress has been made toward this goal in the last 5 years than in the previous five decades. Most of the effort has focused on nitrogenase genes from Klebsiella oxytoca, which has complex gene regulation. There may be advantages in using nitrogenase genes from cyanobacteria, which comprise large polycistronic gene clusters that may be easier to manipulate and eventually express in a plant. The fact that some diatoms have a cyanobacterial nitrogen fixing organelle further supports the idea that a cyanobacterial nitrogenase gene cluster may function in a newly-engineered, cyanobacterial-based plant organelle, a nitroplast. This review describes recent attempts to express the nif genes from Anabaena variabilis ATCC 29413, Leptolyngbya boryana dg5 and Cyanothece sp. ATCC 51142 in heterologous cyanobacteria in the context of the organization of the nitrogenase genes and their regulation by the transcription factor CnfR via its highly conserved binding sites.
Buckling behaviour of trees under self-weight loading
Authors: Dargahi Mojtaba , Newson Timothy , Moore John
Published: April 2019

Understanding tree stability under self-weight and applied loads from wind and snow is important when developing management strategies to reduce the risk of damage from these abiotic agents. In this paper, linear buckling analysis was conducted using the finite element method to identify the instability modes of a tree structure under a specified set of loads. A non-prismatic elastic circular column of height H was analysed, taking self-weight into account. Various scenarios were considered: column taper, base rigidity, radial and longitudinal stiffness, ellipticity and crown weight. The effect on the critical buckling height was assessed in each case. Validation against closed form solutions of benchmark problems was conducted satisfactorily. The results indicate that column taper, base rigidity and the stiffness/density ratio are particularly important for this problem. Further comparison was made using data from a 15-year old Pinus radiata stand in New Zealand, which contained both buckled and non-buckled trees. While the model predicted factors of safety against buckling that were close to unity, it was unable to differentiate between buckled and non-buckled trees. Further investigation is needed to examine the reasons why this occurred. Despite this, the current study provides an in-depth numerical investigation, which has aided our understanding of the effects that material properties, geometric properties and boundary conditions have on buckling phenomenon in trees.
Accounting for uncertain fault geometry in earthquake source inversions – II: application to the Mw 6.2 Amatrice earthquake, central Italy
Authors: Ragon Théa , Sladen Anthony , Simons Mark
Published: April 2019

Our understanding of earthquake sources is limited by the availability and the quality of observations and the fidelity of our physical models. Uncertainties in our physical models will naturally bias our inferences of subsurface fault slip. These uncertainties will always persist to some level as we will never have a perfect knowledge of the Earth’s interior. The choice of the forward physics is thus ambiguous, with the frequent need to fix the value of several parameters such as crustal properties or fault geometry. Here, we explore the impact of uncertainties related to the choice of both fault geometry and elastic structure, as applied to the 2016 Mw 6.2 Amatrice earthquake, central Italy. This event, well instrumented and characterized by a relatively simple fault morphology, allows us to explore the role of uncertainty in basic fault parameters, such as fault dip and position. We show that introducing uncertainties in fault geometry in a static inversion reduces the sensitivity of inferred models to different geometric assumptions. Accounting for uncertainties thus helps infer more realistic and robust slip models. We also show that uncertainties in fault geometry and Earth’s elastic structure significantly impact estimated source models, particularly if near-fault observations are available.
Effects of Digit Orientation on Gecko Adhesive Force Capacity: Synthetic and Behavioral Studies
Authors: Imburgia M J , Kuo C -Y , Briggs D R , Irschick D J , Crosby A J
Published: April 2019

In this study we developed an analytical relationship between adhesive digit orientation and adhesive force capacity to describe the tendencies of climbing organisms that use adhesion for climbing to align their toes in the direction of loading, maximizing adhesive force capacity. We fabricated a multi-component adhesive device with multiple contact surfaces, or digits, to act as a model system mimicking the angular motion of a foot and found the synthetic experiments agree with the developed analytical relationship. In turn, we find that observations of gekkonid lizards climbing on vertical substrates correlate well with our analytical relationship; a reduction in toe spacing is seen on the forelimbs when the animals are facing up. Interestingly, the toes on the hindlimbs tend to have an increase in spacing, possibly a mechanism for stabilization rather than load-bearing.
Mitochondria and the Origin of Species: Bridging Genetic and Ecological Perspectives on Speciation Processes
Authors: Tobler M , Barts N , Greenway R
Published: April 2019

Mitochondria have been known to be involved in speciation through the generation of Dobzhansky–Muller incompatibilities, where functionally neutral co-evolution between mitochondrial and nuclear genomes can cause dysfunction when alleles are recombined in hybrids. We propose that adaptive mitochondrial divergence between populations can not only produce intrinsic (Dobzhansky–Muller) incompatibilities, but could also contribute to reproductive isolation through natural and sexual selection against migrants, post-mating prezygotic isolation, as well as by causing extrinsic reductions in hybrid fitness. We describe how these reproductive isolating barriers can potentially arise through adaptive divergence of mitochondrial function in the absence of mito-nuclear coevolution, a departure from more established views. While a role for mitochondria in the speciation process appears promising, we also highlight critical gaps of knowledge: (1) many systems with a potential for mitochondrially-mediated reproductive isolation lack crucial evidence directly linking reproductive isolation and mitochondrial function; (2) it often remains to be seen if mitochondrial barriers are a driver or a consequence of reproductive isolation; (3) the presence of substantial gene flow in the presence of mito-nuclear incompatibilities raises questions whether such incompatibilities are strong enough to drive speciation to completion; and (4) it remains to be tested how mitochondrial effects on reproductive isolation compare when multiple mechanisms of reproductive isolation coincide. We hope this perspective and the proposed research plans help to inform future studies of mitochondrial adaptation in a manner that links genotypic changes to phenotypic adaptations, fitness, and reproductive isolation in natural systems, helping to clarify the importance of mitochondria in the formation and maintenance of biological diversity.
Prolonged periods of waiting for an asylum decision and the risk of psychiatric diagnoses: a 22-year longitudinal cohort study from Denmark
Authors: Hvidtfeldt Camilla , Petersen Jørgen Holm , Norredam Marie
Published: April 2019

Background

The high prevalence of psychiatric disorders among resettled refugees necessitates identification of factors that reduce the risk of mental illness. In this 22-year longitudinal cohort study, we assessed whether the length of asylum-decision waiting periods is associated with resettled refugees’ risk of being diagnosed with a psychiatric disorder.

Methods

We used full-population data from the Danish Civil Registration System to establish a cohort of 46 104 refugees resettled in Denmark during 1995–2016. Hazard ratios (HRs) for first-time psychiatric hospital contact (ICD-10) after residence permit issuance across varying lengths of asylum-decision waiting periods were estimated by cross-linkage with the Danish National Patient Register.

Results

Long asylum-decision waiting periods were associated with an increased risk of psychiatric disorders. Compared with refugees who waited 0–6 months for their asylum decision, the HRs of any psychiatric diagnosis were 1.22 [95% confidence interval (CI): 1.12–1.33] for those who waited 13–24 months and 1.46 (95% CI: 1.27–1.69) for those who waited 25–71 months. Associations varied across diagnoses and length of follow-up: whereas the risk of nervous disorders increased with longer asylum-decision waiting periods in the follow-ups of 0–2.9, 3–5.9 and 6–11.9 years, the risk of psychotic disorders was associated with longer asylum-decision procedures only in the 0–2.9-year follow-up.

Conclusion

Resettled refugees who waited longer than 1 year for an asylum decision face an increased risk of psychiatric disorders. Host countries should consider that long asylum-decision waiting periods could lead to mental illness among refugees.
Expected Monetary Impact of Oncotype DX Score-Concordant Systemic Breast Cancer Therapy Based on the TAILORx Trial
Authors: Mariotto Angela , Jayasekerea Jinani , Petkov Valentina , Schechter Clyde B , Enewold Lindsey , Helzlsouer Kathy J , Feuer Eric J , Mandelblatt Jeanne S
Published: April 2019

Background

TAILORx demonstrated that women with node-negative, hormone receptor-positive, HER2-negative breast cancers and Oncotype DX recurrence scores (RS) of 0–25 had similar 9-year outcomes with endocrine vs chemo-endocrine therapy; evidence for women aged 50 years and younger and RS 16–25 was less clear. We estimated how expected changes in practice following the trial might affect US costs in the initial 12 months of care (initial costs).

Methods

Data from Surveillance, Epidemiology, and End Results (SEER), SEER-Medicare, and SEER-Genomic Health Inc datasets were used to estimate Oncotype DX testing and chemotherapy rates and mean initial costs pre- and post-TAILORx (in 2018 dollars), assuming all women received Oncotype DX testing and score-suggested therapy posttrial. Sensitivity analyses tested the impact on costs of assumptions about compliance with testing and score-suggested treatment and estimation methods.

Results

Pretrial mean initial costs were $2.816 billion. Posttrial, Oncotype DX testing costs were projected to increase from $115 to $231 million and chemotherapy use to decrease from 25% to 17%, resulting in initial care costs of $2.766 billion, or a net savings of $49 million (1.8% decrease). A small net savings was seen under most assumptions. The one exception was if all women aged 50 years and younger with tumors with RS 16–25 elected to receive chemotherapy, initial care costs could increase by $105 million (4% increase).

Conclusions

Personalizing breast cancer treatment based on tumor genetic profiles could result in small cost decreases in the initial 12 months of care. Studies are needed to evaluate the long-term costs and nonmonetary benefits of personalized cancer care.
Fighting about Women: Ideologies of Gender in the Syrian Civil War
Authors: Szekely Ora
Published: April 2019

This article seeks to map and explain the sudden increase in the appearance of female combatants in the propaganda distributed by various parties to the Syrian civil war. Based on interviews and the analysis of online propaganda, the article argues that the importance of ideologies of gender to two of the four main participants in the Syrian civil war (specifically, the Kurdish Partiya Yekîtiya Demokrat, PYD, and the Islamic State, or ISIS) has rendered gender ideology an unusually salient point of ideological cleavage in the Syrian context. This has meant that other parties to the conflict, for whom gender ideology is less important, are able to easily signal their position in relation to other conflict participants by means of policies or actions relating to women's participation in the conflict.
Soft Rejuvenation: Cosmetics, Idealized White Femininity, and Young Women’s Bodies, 1880–1930
Authors: Smith Michelle J , Nicholas Jane
Published: April 2019

In this article we draw together the histories of rejuvenation and cosmetic use in order to examine discourses of “soft rejuvenation” in the late nineteenth and early twentieth centuries. While rejuvenation has typically been considered in relation to transnational medicalized attempts to restore youthful vitality and virility, we suggest that the logic of rejuvenation was feminized through the promotion of cosmetic and daily self-care regimens in this period. Drawing on material from British, American, and Canadian contexts relating to beauty and hygiene, we suggest that daily practices of caring for and disciplining the white female body, especially through cosmetic use, were legitimated, in part, using the rhetoric of rejuvenation. The article considers how the transnational, the modern, and the propagation of whiteness in the early twentieth century were mobilized in these ideas of how daily bodily work could preserve the (white) youthful face and body, which was understood to embody health and vigor. This discourse was significant for young women, who were subject to male control over their bodies as they began to be employed in nontraditional workplaces; however, we also argue that these cosmetic practices can be understood as a component of girls’ and women’s own self-fashioning of modern identities.
Ultraluminous X-ray sources with flat-topped noise and QPO
Authors: Atapin Kirill , Fabrika Sergei , Caballero-García Maria D
Published: April 2019

We analysed the X-ray power density spectra of five ultraluminous X-ray sources (ULXs) NGC 5408 X-1, NGC 6946 X-1, M 82 X-1, NGC 1313 X-1, and IC 342 X-1 that are the only ULXs that display both flat-topped noise (FTN) and quasi-periodic oscillations (QPOs). We studied the QPO frequencies, fractional root-mean-square (rms) variability, X-ray luminosity, and spectral hardness. We found that the level of FTN is anticorrelated with the QPO frequency. As the frequency of the QPO and brightness of the sources increase, their fractional variability decreases. We propose a simple interpretation using the spherization radius, viscosity time, and α-parameter as basic properties of these systems. The main physical driver of the observed variability is the mass accretion rate that varies ≳3 between different observations of the same source. As the accretion rate decreases the spherization radius reduces and the FTN plus the QPO move towards higher frequencies, resulting in a decrease of the fractional rms variability. We also propose that in all ULXs when the accretion rate is low enough (but still super-Eddington) the QPO and FTN disappear. Assuming that the maximum X-ray luminosity depends only on the black hole (BH) mass and not on the accretion rate (not considering the effects of either the inclination of the super-Eddington disc or geometrical beaming of radiation), we estimate that all the ULXs have about similar BH masses, with the exception of M 82 X-1, which might be 10 times more massive.
Constraining the Milky Way halo potential with the GD-1 stellar stream
Authors: Malhan Khyati , Ibata Rodrigo A
Published: April 2019

We use ESA/Gaia astrometry together with SEGUE and LAMOST measurements of the GD-1 stellar stream to explore the improvement on the Galactic gravitational potential that these new data provide. Assuming a realistic universal model for the dark matter halo together with reasonable models of the baryonic components, we find that the orbital solutions for GD-1 require the circular velocity at the Solar radius to be $V_{\rm circ}({\rm R}_\odot) =244\pm 4{\rm \, km\, s^{-1}}$, and also that the density flattening of the dark halo is $q_{\rho }=0.82^{+0.25}_{-0.13}$. The corresponding Galactic mass within $20{\rm \, kpc}$ was estimated to be $M_{\rm MW}(\lt 20{\rm \, kpc})=2.5\pm 0.2 \times 10^{11} {\rm \, M_\odot }$. Moreover, Gaia’s excellent proper motions also allowed us to constrain the velocity dispersion of the GD-1 stream in the direction tangential to the line of sight to be $\lt 2.30{\rm \, km\, s^{-1}}$ (95 per cent confidence limit), confirming the extremely cold dynamical nature of this system.
2MASS J10274572+0629104: the very short period young M6 dwarf binary system identified in K2 data
Authors: Paudel R R , Gizis J E , Burgasser A J , Hsu C
Published: April 2019

We report the identification of a very low mass new binary system 2MASS J10274572+0629104, based on Kepler K2 photometry and Gaia DR2 astrometry. It is located at a distance of 90.0 ± 2.9 pc. The K2 light curve is consistent with a beat pattern of two periodic signals, and using Lomb–Scargle periodogram, we find two rotation periods of 0.2114 ± 0.0002 and 0.2199 ± 0.0003 d. We conclude that these rotation periods arise from two stars with similar spectral types of M6, and have nearly equal luminosity. It is the first ultracool binary system to be identified based on beat patterns in the light curve. Near-infrared spectroscopy yields RV = −9.8 ± 0.6 km s−1, v sin i = 21.5 ± 1.1 km s−1, Teff = 3110 ± 40 K, and log g = 5.2 ± 0.2. The motions are consistent with a young age, as are the rotation periods, but the source does not appear to be part of any known moving group. Furthermore, we detected three strong white light flares in the K2 light curve, with estimated total (UV/optical/IR) energies of 2.6 × 1033, 5.0 × 1033, and 3.5 × 1033 erg, respectively.
Bayesian Inference of Evolutionary Histories under Time-Dependent Substitution Rates
Authors: Membrebe Jade Vincent , Suchard Marc A , Rambaut Andrew , Baele Guy , Lemey Philippe
Published: April 2019

Many factors complicate the estimation of time scales for phylogenetic histories, requiring increasingly complex evolutionary models and inference procedures. The widespread application of molecular clock dating has led to the insight that evolutionary rate estimates may vary with the time frame of measurement. This is particularly well established for rapidly evolving viruses that can accumulate sequence divergence over years or even months. However, this rapid evolution stands at odds with a relatively high degree of conservation of viruses or endogenous virus elements over much longer time scales. Building on recent insights into time-dependent evolutionary rates, we develop a formal and flexible Bayesian statistical inference approach that accommodates rate variation through time. We evaluate the novel molecular clock model on a foamy virus cospeciation history and a lentivirus evolutionary history and compare the performance to other molecular clock models. For both virus examples, we estimate a similarly strong time-dependent effect that implies rates varying over four orders of magnitude. The application of an analogous codon substitution model does not implicate long-term purifying selection as the cause of this effect. However, selection does appear to affect divergence time estimates for the less deep evolutionary history of the Ebolavirus genus. Finally, we explore the application of our approach on woolly mammoth ancient DNA data, which shows a much weaker, but still important, time-dependent rate effect that has a noticeable impact on node age estimates. Future developments aimed at incorporating more complex evolutionary processes will further add to the broad applicability of our approach.
Transcription attenuation-derived small RNA rnTrpL regulates tryptophan biosynthesis gene expression in trans
Authors: Melior Hendrik , Li Siqi , Madhugiri Ramakanth , Stötzel Maximilian , Azarderakhsh Saina , Barth-Weber Susanne , Baumgardt Kathrin , Ziebuhr John , Evguenieva-Hackenberg Elena
Published: April 2019

Ribosome-mediated transcription attenuation is a basic posttranscriptional regulation mechanism in bacteria. Liberated attenuator RNAs arising in this process are generally considered nonfunctional. In Sinorhizobium meliloti, the tryptophan (Trp) biosynthesis genes are organized into three operons, trpE(G), ppiD-trpDC-moaC-moeA, and trpFBA-accD-folC, of which only the first one, trpE(G), contains a short ORF (trpL) in the 5′-UTR and is regulated by transcription attenuation. Under conditions of Trp sufficiency, transcription is terminated between trpL and trpE(G), and a small attenuator RNA, rnTrpL, is produced. Here, we show that rnTrpL base-pairs with trpD and destabilizes the polycistronic trpDC mRNA, indicating rnTrpL-mediated downregulation of the trpDC operon in trans. Although all three trp operons are regulated in response to Trp availability, only in the two operons trpE(G) and trpDC the Trp-mediated regulation is controlled by rnTrpL. Together, our data show that the trp attenuator coordinates trpE(G) and trpDC expression posttranscriptionally by two fundamentally different mechanisms: ribosome-mediated transcription attenuation in cis and base-pairing in trans. Also, we present evidence that rnTrpL-mediated regulation of trpDC genes expression in trans is conserved in Agrobacterium and Bradyrhizobium, suggesting that the small attenuator RNAs may have additional conserved functions in the control of bacterial gene expression.
OCCUPATIONAL EXPOSURE ASSESSMENT AT A THERAPEUTIC RADON SPA FACILITY IN HUNGARY
Authors: Kavasi Norbert , Csordas Anita , Nagy Katalin , Beltran Silvana , Kikaj Dafina , Vaupotič Janja , Kovacs Tibor
Published: April 2019

In order to estimate occupational exposure of workers in a therapeutic radon spa facility, radon concentration in the workplace air was investigated at Markhot Ferenc Hospital, Eger, Hungary. The investigated balneotherapeutic facility and its natural hot spa water are used for treatments and rehabilitations of rheumatic patients. Radon concentration, radon decay products at a bathhouse, treatment rooms and a consultation room were continuously measured in August and September 2018. In the present study, different levels of radon concentration among the observation sites and its clear temporal variations were found, though radon concentrations in the investigated sites were below 300 Bq m−3. Regarding such radon fluctuation and low equilibrium factor level (0.1), the annual effective doses of workers are estimated to be around 0.5 mSv year−1.
Assessing Drug-Induced Long QT and Proarrhythmic Risk Using Human Stem-Cell-Derived Cardiomyocytes in a Ca2+ Imaging Assay: Evaluation of 28 CiPA Compounds at Three Test Sites
Authors: Lu Hua Rong , Zeng Haoyu , Kettenhofen Ralf , Guo Liang , Kopljar Ivan , van Ammel Karel , Tekle Fetene , Teisman Ard , Zhai Jin , Clouse Holly , Pierson Jennifer , Furniss Michael , Lagrutta Armando , Sannajust Frederick , Gallacher David J
Published: April 2019

The goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health and Environmental Sciences Institute (HESI) was to evaluate the utility of an additional in vitro assay technology to detect potential drug-induced long QT and torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients in human stem-cell-derived cardiomyocytes (hSC-CMs). The potential proarrhythmic risks of the 28 comprehensive in vitro proarrhythmia assay (CiPA) drugs linked to low, intermediate, and high clinical TdP risk were evaluated in a blinded manner using Ca2+-sensitive fluorescent dye assay recorded from a kinetic plate reader system (Hamamatsu FDSS/µCell and FDSS7000) in 2D cultures of 2 commercially available hSC-CM lines (Cor.4U and CDI iCell Cardiomyocytes) at 3 different test sites. The Ca2+ transient assay, performed at the 3 sites using the 2 different hSC-CMs lines, correctly detected potential drug-induced QT prolongation among the 28 CiPA drugs and detected cellular arrhythmias-like/early afterdepolarization in 7 of 8 high TdP-risk drugs (87.5%), 6 of 11 intermediate TdP-risk drugs (54.5%), and 0 of 9 low/no TdP-risk drugs (0%). The results were comparable among the 3 sites and from 2 hSC-CM cell lines. The Ca2+ transient assay can serve as a user-friendly and higher throughput alternative to complement the microelectrode array and voltage-sensing optical action potential recording assays used in the HESI-CiPA study for in vitro assessment of drug-induced long QT and TdP risk.
Generalization asymmetry in multivariate cross-classification: When representation A generalizes better to representation B than B to A
Authors: van den Hurk Job , Op de Beeck Hans P.
Published: April 2019

In recent years, the use of multivariate cross-classification (MVCC) has grown in popularity as a way to test for the consistency of information in neural patterns of activation across cognitive states. In this approach, a classification algorithm is trained on dataset A and then tested on a different dataset B in order to test for commonalities in the information representation in both datasets. Interestingly, several papers report an asymmetry in the generalization direction: training on A and testing on B returns significantly better decoding results than training on B and testing on A. Whereas several neurocognitive hypotheses have been put forward as an explanation for this phenomenon, none of them has been demonstrated directly. Through simple simulations, we show that asymmetry can arise as soon as two datasets with identical ground truths have a different signal-to-noise ratio (SNR) – generalization is best from the lower SNR to the higher SNR dataset. The extent of the asymmetry is further modulated by the overlap in informative voxels and whether the two datasets have an equal number of informative voxels. These findings demonstrate that the observation of decoding direction asymmetry in MVCC can be explained by simple SNR differences and not necessarily implies complex neurocognitive mechanisms.
Gene-methylation interactions: Discovering region-wise DNA methylation levels that modify SNP-associated disease risk
Authors: Romanowska Julia , Haaland Øystein A. , Jugessur Astanand , Gjerdevik Miriam , Xu Zongli , Taylor Jack , Wilcox Allen J. , Jonassen Inge , Lie Rolv Terje , Gjessing Håkon K.
Published: April 2019

The genetic code is tightly linked to epigenetic instructions as to what genes to express, and when and where to express them. The most studied epigenetic mark is DNA methylation at CpG dinucleotides. Today’s technology enables a rapid assessment of DNA sequence and methylation levels at a single-site resolution for hundreds of thousands of sites in the human genome, in thousands of individuals at a time. Recent years have seen a rapid increase in epigenome-wide association studies (EWAS) searching for the causes of risk for genetic diseases that previous genome-wide association studies (GWAS) could not pinpoint. However, those single-omics data analyses led to even more questions and it has become clear that only by integrating data one can get closer to answers. Here, we propose two new methods within genetic association analyses that treat the level of DNA methylation at a given CpG site as environmental exposure. Our analyses search for statistical interactions between a given allele and DNA methylation (G×Me), and between a parent-of-origin effect and DNA methylation (PoO× Me). The new methods were implemented in the R package Haplin and were tested on a dataset comprising genotype data from mother-father-child triadsm with DNA methylation data from the children only. The phenotype here was orofacial clefts (OFC), a relatively common birth defect in humans, which is known to have a genetic origin and an environmental component possibly mediated by DNA methylation. We found no significant PoO×Me interactions and a few significant G×Me interactions. Our results show that the significance of these interaction effects depends on the genomic region in which the CpGs reside and on the number of strata of methylation level. We demonstrate that, by including the methylation level around the SNP in the analyses, the estimated relative risk of OFC can change significantly. We also discuss the importance of including control data in such analyses. The new methods will be of value for all the researchers who want to explore genome- and epigenome-wide datasets in an integrative manner. Moreover, thanks to the implementation in a popular R package, the methods are easily accessible and enable fast scans of the genome- and epigenome-wide datasets.
Comparing open-source toolboxes for processing and analysis of spike and local field potentials data
Authors: Unakafova Valentina A. , Gail Alexander
Published: April 2019

Analysis of spike and local field potential (LFP) data is an essential part of neuroscientific research. Today there exist many open-source toolboxes for spike and LFP data analysis implementing various functionality. Here we aim to provide a practical guidance for neuroscientists in the choice of an open-source toolbox best satisfying their needs. We overview major open-source toolboxes for spike and LFP data analysis as well as toolboxes with tools for connectivity analysis, dimensionality reduction and generalized linear modeling. We focus on comparing toolboxes functionality, statistical and visualization tools, documentation and support quality. To give a better insight, we compare and illustrate functionality of the toolboxes on open-access dataset or simulated data and make corresponding MATLAB scripts publicly available.