bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Two‐Analyte Population Pharmacokinetic Model of Polatuzumab Vedotin in Patients With Non‐Hodgkin Lymphoma
Authors: Lu Dan , Lu Tong , Gibiansky Leonid , Li Xiaobin , Li Chunze , Agarwal Priya , Shemesh Colby S. , Shi Rong , Dere Randall C. , Hirata Jamie , Miles Dale , Chanu Pascal , Girish Sandhya , Jin Jin Yan
Published: November 2019

A two‐analyte integrated population pharmacokinetic (PK) model that simultaneously describes concentrations of antibody‐conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE following repeated administrations of polatuzumab vedotin (pola) was developed based on data from four clinical studies of pola in patients with non‐Hodgkin lymphoma. A two‐compartment model with a nonspecific, time‐dependent linear clearance, a linear time‐dependent exponentially declining clearance, and a Michaelis–Menten clearance provided a good fit of the acMMAE plasma PK profiles. All three acMMAE elimination pathways contributed to the input to the central compartment of unconjugated MMAE, which was also described by a two‐compartment model. Population PK parameters, covariate effects, and interindividual variability of model parameters were estimated. The impact of clinically relevant covariates on PK exposures of each analyte were quantified and reported to support key label claims.
Identification of the influential parts in a complex mechanical product from a reliability perspective using complex network theory
Authors: Yin Xiaoqing , Mo Yudi , Dong Chenchen , Zhang Yuhong
Published: November 2019

Due to the difference in the numbers and strengths of physical relationships among parts, complex mechanical products (CMPs) have community structure characteristics. There are often some influential parts in the community. Failures of these influential parts spread rapidly along the physical relationships between parts in the community, which seriously affects the reliability of a product. Therefore, identifying the influential parts in the community and adopting targeted measures can effectively improve the reliability and service life of a product. However, identifying the influential parts within each community in a collection of parts with complex relationships is very difficult. Thus, from the perspective of reliability, a method for identifying the influential parts of a CMP based on complex network theory is proposed and used to identify the influential parts in each community of products. First, weighted complex network (WCN) theory is employed to construct a CMP into a WCN model. Second, the complex network community detection method is employed to detect the community structure of the WCN model. Third, a modified LocalRank algorithm is employed to identify the influential nodes in each community, ie, the influential parts in each community of a CMP. Fourth, a modified susceptible‐infectious‐recovered (SIR) model is employed to evaluate the impacts of the influential parts. An analysis of a company's DC drill planetary gearbox shows that the proposed method is accurate and effective.
Charge migration fragmentation in the negative ion mode of cyclopentenone and cyclopentanone intermediates in the biosynthesis of jasmonates
Authors: Oliw Ernst H. , Hamberg Mats
Published: November 2019

Rationale

Jasmonates are formed from 12‐oxo‐10,15(Z)‐phytodienoic acid (12‐OPDA) in plants and also from 12‐oxo‐10‐phytoenoic acid (12‐OPEA) in fungi. Collision‐induced dissociation (CID) of [M‐H]− generates characteristic product anions at m/z 165 [C11H17O]−. Our goal was to investigate the structure and mode of formation of this anion by CID of 12‐OPDA, 12‐OPEA, and 12‐oxophytonoic acid (12‐OPA).

Methods

We investigated the CID of the [M‐H]−, [M‐H‐CO2]−, and [M‐H‐H2O]− anions using electrospray ionization and MS/MS analysis of 12‐OPDA, 12‐OPEA, and 12‐OPA, and compared the results with the data obtained with the corresponding compounds labeled with 2H at C‐6 and C‐7 and with structural and side chain analogs.

Results

CID of [6,6,7,7‐2H4]12‐OPEA and [6,6‐2H2]12‐OPDA ([M‐H]− and [M‐H‐CO2]−) showed that one or two 2H atoms were transferred to anions at m/z 165 as judged by the signal intensities of m/z 165 + 1 or 165 + 2, respectively. CID of [6,6‐2H2]‐ and [6,6,7,7‐2H4]‐12‐OPA ([M‐H]− and [M‐H‐CO2]−) yielded the loss of H2 from the cyclopentanone and displayed the transfer of one 2H atom in analogy to 12‐OPEA. In contrast, CID of [6,6,7,7‐2H4]12‐OPEA and [6,6,7,7‐2H4]12‐OPA [M‐H‐H2O]− demonstrated the transfer of two 2H atoms (m/z 165 + 2). All spectra obtained by CID of [6,6,7,7‐2H4]12‐OPDA and [6,6,7,7‐2H4]12‐oxo‐9(13),15(Z)‐phytodienoic acid showed that one or two additional 2H atoms could be transferred to this anion at m/z 167 of [6,6‐2H2]12‐OPDA due to isotope scrambling.

Conclusions

CID of 12‐OPDA and 12‐OPEA generates cyclopentanone enolate anions at m/z 165 by charge‐driven hydride transfer as a common mechanism and by bond cleavage between C‐7 and C‐8 of the carboxyl side chains with either gain or loss of a hydrogen atom.
Jumping spectra and vanishing couplings in heterotic Line Bundle Standard Models
Authors: Gray James , Wang Juntao
Published: November 2019

Abstract

We study two aspects of the physics of heterotic Line Bundle Standard Models on smooth Calabi-Yau threefolds. First, we investigate to what degree modern moduli stabilization scenarios can affect the standard model spectrum in such compactifications. Specifically, we look at the case where some of the complex structure moduli are fixed by a choice of hidden sector bundle. In this context, we study the frequency with which the system tends to be forced to a point in moduli space where the cohomology groups determining the spectrum in the standard model sector jump in dimension. Second, we investigate to what degree couplings, that are permitted by all of the obvious symmetries of the theory, actually vanish due to certain topological constraints associated to their higher dimensional origins. We find that both effects are prevalent within the data set of heterotic Line Bundle Standard Models studied.
Process variable optimization in the cold metal transfer weld repair of aerospace ZE41A-T5 alloy using central composite design
Authors: Ola O. T. , Valdez R. L. , Oluwasegun K. M. , Ojo O. A. , Chan K. , Birur A. , Cuddy J.
Published: November 2019

The pulsed cold metal transfer (CMT+P) process was evaluated for the repair of aerospace structural components made from ZE41A-T5 magnesium alloy. The choice of welding variables was considered to be unique for the material type, weld design and geometry, and application-specific requirements. A design of experiment (DOE) method based on a rotatable 3D central composite design (CCD) was used to systematically establish relationships between independent welding variables and the resultant output variables of the CMT+P process, including the development of mathematical models based on second-order polynomial. A multiple response desirability function approach was then used for process optimization. The CMT+P process produced high-quality welds in the alloy. Welding process variables were established to produce desired weld penetration and weld reinforcement and complete fusion with minimal weld defects. Optimal domains of the independent variables were achieved; where the welds comply with the application-specific (repair of gearbox housing) requirements and acceptable class A weld quality of the aerospace fusion welding standard AWS D17.1.
The current situation of canine dirofilariosis in Hungary
Authors: Farkas Róbert , Mag Viktória , Gyurkovszky Mónika , Takács Nóra , Vörös Károly , Solymosi Norbert
Published: November 2019

Between April and September 2017, blood samples were collected from 344 randomly selected dogs older than 1 year in 180 settlements of 19 counties in Hungary. The dogs lived exclusively outdoors, had never travelled and had neither been examined for Dirofilaria infection nor treated against mosquitoes with insecticides or/and filarioid worms with macrocyclic lactones. Dirofilaria infection was examined with a modified Knott’s test for microfilariae, DiroCHEK®, for the presence of D. immitis antigen, as well as by multiplex and conventional PCR. Altogether, 77 (22.4%) dogs living in 58 settlements of 17 counties were found to be infected with one or both Dirofilaria species based on the PCR techniques. Twenty-eight (8.1%) and 38 (11.1%) dogs were infected with D. immitis and D. repens, respectively. Coinfections were recorded in 11 samples (3.2%) collected in 11 locations of 8 counties. The results confirmed that both dirofilarioses are endemic in dogs and the eastern areas of the country are hyperendemic for heartworm disease. Temperature showed a significant association with the prevalence of D. immitis (OR 2.41, 95% CI 1.24–4.86, p = 0.012) but not with that of D. repens (OR 1.37, 95% CI 0.78–2.47, p = 0.286). The prevalence of neither D. immitis (OR 0.99, 95% CI 0.98–1.00, p = 0.213) nor D. repens (OR 1.01, 95% CI 0.99–1.01, p = 0.094) showed a significant correlation with precipitation. The number of yearly growing degree days (GDD) based on the lifecycle of Dirofilaria in mosquitoes ranged between 3.73 and 7.57 for the Hungarian districts. The GDD showed a significant positive association with the prevalence of D. immitis (OR 2.38, 95% CI 1.43–4.15, p = 0.001) and a non-significant positive relationship with that of D. repens (OR 1.25, 95% CI 0.83–1.95, p = 0.291).
Multivalued decision diagrams for prize-collecting job sequencing with one common and multiple secondary resources
Authors: Maschler Johannes , Raidl Günther R.
Published: November 2019

Multivalued decision diagrams (MDD) are a powerful tool for approaching combinatorial optimization problems. Relatively compact relaxed and restricted MDDs are applied to obtain dual bounds and heuristic solutions and provide opportunities for new branching schemes. We consider a prize-collecting sequencing problem in which a subset of given jobs has to be found that is schedulable and yields maximum total prize. The primary aim of this work is to study different methods for creating relaxed MDDs for this problem. To this end, we adopt and extend the two main MDD compilation approaches found in the literature: top down construction and incremental refinement. In a series of computational experiments these methods are compared. The results indicate that for our problem the incremental refinement method produces MDDs with stronger bounds. Moreover, heuristic solutions are derived by compiling restricted MDDs and by applying a general variable neighborhood search (GVNS). Here we observe that the top down construction of restricted MDDs is able to yield better solutions as the GVNS on small to medium-sized instances.
Development and application of a forensic toxicological library for identification of 56 natural toxic substances by liquid chromatography–quadrupole time-of-flight mass spectrometry
Authors: Ogawa Tadashi , Zaitsu Kei , Kokaji Tetsuo , Suga Kayako , Kondo Fumio , Iwai Masae , Suzuki Takayoshi , Ishii Akira , Seno Hiroshi
Published: November 2019

Purpose

The present study aims to develop a forensic toxicological library to identify 56 natural toxic substances by liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (LC–QTOF-MS/MS).

Methods

For setting up the library of product ion spectra, individual substances (31 plant toxins, 7 mushroom toxins, 5 marine toxins, 5 frog venoms, 4 mycotoxins, and 4 substances derived from plants) were analyzed by LC–QTOF-MS/MS with positive and negative ionization. The product ion spectra were acquired at the collision energies (CEs) of 20, 35, and 50 eV in single enhanced product ion mode and then in collision energy spread mode in which the CE ramp range was set to 35 ± 15 eV.

Results

To test the performance of the library, human blood plasma samples were spiked with a mixture of lycorine and domoic acid, extracted by acetonitrile deproteinization and analyzed by LC–QTOF-MS/MS. Identification by our library search could be achieved for these toxins at the purity scores of 79.1 and 67.2, respectively. The method was also applied to postmortem blood from a death case with an aconite intake, and showed that four toxins in an aconite could be identified in the blood sample at the purity scores of 54.6–60.3.

Conclusions

This library will be more effective for the screening of natural toxic substances in routine forensic toxicological analysis. To our knowledge, there are no reports dealing with development of library for natural toxic substances by LC–QTOF-MS/MS.
A call for action: understanding medicine’s role in climate change
Authors: Nuttall Ciara , Yaqub Fatima
Published: November 2019

None
Deep learning for plankton and coral classification
Authors: Lumini Alessandra , Nanni Loris , Maguolo Gianluca
Published: November 2019

In this paper, we present a study about an automated system for monitoring underwater ecosystems. The system here proposed is based on the fusion of different deep learning methods. We study how to create an ensemble based of different Convolutional Neural Network (CNN) models, fine-tuned on several datasets with the aim of exploiting their diversity. The aim of our study is to experiment the possibility of fine-tuning CNNs for underwater imagery analysis, the opportunity of using different datasets for pre-training models, the possibility to design an ensemble using the same architecture with small variations in the training procedure.

Our experiments, performed on 5 well-known datasets (3 plankton and 2 coral datasets) show that the combination of such different CNN models in a heterogeneous ensemble grants a substantial performance improvement with respect to other state-of-the-art approaches in all the tested problems. One of the main contributions of this work is a wide experimental evaluation of famous CNN architectures to report the performance of both the single CNN and the ensemble of CNNs in different problems. Moreover, we show how to create an ensemble which improves the performance of the best single model. The MATLAB source code is freely link provided in title page.
Cardiac hydatid disease; misleading presentations, a case series
Authors: Oraha Ashur Y. , Al-modhaffer Saif Sami , Ahmed Okba F. , Al obaidy Wisam S. , Baram Aram , Kakamad Fahmi , Yaldo Fitoon F.
Published: November 2019

ABSTRACT

Introdcution:

Cardiac echinococcosis is a zoonotic parasitic infection that necessitates a high index of suspicion in endemic areas. The purpose of this study is to introduce different clinical scenarios of four cases in two major cardiac centers.

Methods:

A retrospective, case series study, conducted in three centers for the last two years. Addressing each case separately in regard to presentation and management.

Results:

Four cases have been reported, three patients were female 75% and one patient was male 25%. Age ranged from 27 to 32 years. All the patients 100% had dyspnea as their main first presentation, one patient (25%) presented as pulmonary embolism with three attacks of hemoptysis. One patient (25%) had an attack of convulsion 25%. Different segments of the heart were involved, Left ventricle was involved in 50%, Right ventricle in 25%, combined pulmonary and pericardial involvement in another 25%. Median Sternotomy with the cardioplegic arrest was performed in three patients 75% and Posterolateral thoracotomy was the approach in one case 25%.

Conclusion:

Cardiac Hydatid cyst is a sparse yet potentially perilous clinical entity. Early surgical intervention is the modality of choice might halt unfavorable consequences.

Highlights:
Impact of the Advent of Collagenase Clostridium Histolyticum on the Surgical Management of Peyronie’s Disease: A Population-Based Analysis
Authors: Sukumar Shyam , Pijush Debduth Bardhan , Brandes Steven
Published: November 2019

Introduction

Penile plication or partial excision with grafting has traditionally been the first-line treatment for stable Peyronie’s disease (PD). Numerous injection therapies (ITs) have been introduced over the last few decades. Intralesional collagenase clostridium histolyticum (CCH) was U.S. Food and Drug Administration approved in 2013 for patients with stable disease, curvature ≥30° and ≤90°, and intact erectile function. The impact of the advent of CCH on the surgical management of PD is unknown.

Aim

We studied the effect of IT on the surgical management of PD in a population-based analysis.

Methods

The Statewide Planning and Research Cooperative System database, which provides statewide level of all-payer data on patients in the outpatient, inpatient, ambulatory, and emergency department setting in New York State was reviewed. Patients undergoing a penile prosthesis for concurrent erectile dysfunction were excluded.

Main Outcome Measure

Descriptive statistics and multivariable logistic regression modeling were used to assess factors influencing choice of injection therapy vs surgical therapy (penile plication or partial excision with grafting).

Results

From 2003−2016, 547 patients with PD presented for management. Median age was 56 years and 57% were white. Over the study period, surgical management was used less often as the primary procedure with a concurrent increase in use of IT (P < .001). On multivariable modeling, patients more likely to receive IT as treatment for penile curvature were younger (odds ratio [OR]: 1.26; P = .002; CI: 1.09−1.46), of higher socioeconomic status (OR: 1.14; P = .037; CI: 1.01−1.29), presented in the post-CCH era (OR: 1.17; P = .018; CI: 1.03−1.33) and presented to a surgeon with a high volume practice (OR: 1.25; P = .007; CI: 1.07−1.48). Patients presenting in the post-CCH era were 17% significantly more likely to receive IT.

Clinical Implications

ITs like CCH are increasingly displacing surgical management as the primary treatment option of Peyronie’s disease.

Strengths & Limitations

The Statewide Planning and Research Cooperative System database is particularly useful for this analysis because it is an all-payer database that tracks patients longitudinally across various health care settings—outpatient and inpatient. Limitations: It only includes patients in New York State limiting generalizability. The retrospective nature of the analysis makes it subject to the biases inherent in such reports. Specific disease level characteristics (eg, degree of curvature, duration of disease, and associated deformities) were not available.

Conclusion

Since the introduction of CCH, there has been a markedly decreasing trend in the utilization of surgery as the primary modality in the management of PD-associated penile curvature.
Creating poetry from the BAS archives: Commentary on, and extracts from, a new poetic sequence, “Met Obs”
Authors: Lewis Williams Elizabeth
Published: November 2019

The Antarctic Treaty of 1959, which dedicates the continent to peace and international scientific cooperation in the face of rising east–west tensions, is informed in part by a shared scientific imaginary created by the UK and other nations which maintained scientific bases in Antarctica at the time. In this article, the poet offers works extracted from her longer sequence “Met Obs,” based on meteorological reports and journals from the UK station at Port Lockroy written in advance of the 1957–1958 International Geophysical Year (IGY). The poems engage with the work and circumstances which helped foster such an imaginary, as well as with the nexus of Antarctic “values” endorsed by the Treaty, and the later Madrid Protocol. The commentary further contextualises these literary responses in terms of the attitudes of the men working there as well as the “wilderness and aesthetic values” recognised by the later Protocol on Environmental Protection. The world of the poems may belong to 1950s Antarctica, but their observations reach beyond that experience, making a case for the continued relevance of Treaty values, and for the importance of artistic, as well as scientific, responses to the environment in a world under threat from accelerating climate change and competition for resources.
The He++/H+ Density Ratio Across Earth's Subsolar Magnetopause and Its Implications for the Presence of a Mass‐Dependent Reflection Coefficient
Authors: Delano K. , Fuselier S.A. , Elliott H.A. , Burch J.L. , Mukherjee J. , Petrinec S. , Strangeway R.J. , Trattner K.J.
Published: November 2019

When magnetic reconnection is occurring at Earth's magnetopause, incident magnetosheath ions are either reflected or transmitted, and the likelihood of each outcome is quantified by the reflection coefficient. This statistical study reexamines the question of whether or not the reflection coefficient is mass dependent by observing the He++/H+ density ratio at magnetopause crossings. High‐resolution data from the Hot Plasma Composition Analyzer on board the Magnetospheric Multiscale spacecraft are used from its Mission Phase 1a. We analyze these new measurements of the relative changes in the He++/H+ density ratio across the boundary layers of the magnetopause for a restricted set of solar wind conditions. From this analysis, we conclude that, for southward IMF, the reflection coefficient has no dependence on mass.
Virtual Sources and Receivers in the Real Earth: Considerations for Practical Applications
Authors: Brackenhoff Joeri , Thorbecke Jan , Wapenaar Kees
Published: November 2019

To enhance monitoring of the subsurface, virtual sources and receivers inside the subsurface can be created from seismic reflection data at the surface of the Earth using the Marchenko method. The response between these virtual sources and receivers can be obtained through the use of homogeneous Green's function retrieval. A homogeneous Green's function is a superposition of a Green's function and its time reversal. The main aim of this paper is to obtain accurate homogeneous Green's functions from field data. Classical homogeneous Green's function retrieval requires an unrealistic enclosing recording surface; however, by using a recently proposed single‐sided retrieval scheme, this requirement can be avoided. We first demonstrate the principles of using the single‐sided representation on synthetic data and show that different source signatures can be taken into account. Because the Marchenko method is sensitive to recording limitations of the reflection data, we study five cases of recording limitations with synthetic data and demonstrate their effects on the final result. Finally, the method is demonstrated on a preprocessed field data set that fulfills the requirements for applying the single‐sided Green's function retrieval scheme. The scheme has the potential to be used in future applications, such as source localization.
Characterization of Deltaic Channel Morphodynamics From Imagery Time Series Using the Channelized Response Variance
Authors: Jarriel Teresa , Isikdogan Leo F. , Bovik Alan , Passalacqua Paola
Published: November 2019

River deltas are complex, dynamic systems whose channel networks evolve in response to internal and external forcings. To capture these changes, methods to extract and analyze deltaic morphodynamics automatically using available remotely sensed imagery and experimental observations are needed. Here, we apply a promising method for the automatic extraction of channel presence called RivaMap, on both synthetic and experimental data sets, to investigate the changes experienced by the system in response to five changes in forcings. RivaMap is an automated method to extract nonbinarized channel locations from imagery based on a singularity index that combines the multiscale first and second derivatives of the image intensity to favor the identification of curvilinear features and suppress edges. We quantify how the channelization varies by computing the channelized response variance (CRV), which we define as the variance of each pixel's singularity index response through time. We find that increasing magnitudes of sediment inflow (Qs) and water inflow (Qw) result in corresponding increases in the maximum CRV. We find that increasing the ratio of Qs to Qw results in increased number of channelized areas. We see that adding cohesion to the exposed sediment surface of the experimental delta results in decreased magnitude and decreased number of channelized areas in the CRV. Finally, by observing changes to the CRV over time, we are able to quantify the timescale of internal channel reorganization events as the experimental delta evolves under constant forcings.
Tidal Flow Asymmetry and Discharge of Lateral Tributaries Drive the Evolution of a Microtidal Meander in the Venice Lagoon (Italy)
Authors: Finotello Alvise , Canestrelli Alberto , Carniello Luca , Ghinassi Massimiliano , D'Alpaos Andrea
Published: November 2019

Tidal landscapes are extensively characterized by the presence of meandering channels, the latter being important for the ecomorphodynamic evolution of these environments. It remains unclear whether changes in the relative strength of maximum flood and ebb currents (i.e., tidal flow asymmetries), together with the widespread presence of lateral tributaries, cause tidal meanders to evolve differently from their fluvial relatives. Here, we investigate the evolution of a meandering channel in the Venice Lagoon (Italy) that receives water from two major tributaries along its outer bank. Using a 2‐D numerical model, we first analyze the changes in local tidal flow asymmetries, both natural and anthropogenically induced, which occurred during the last 120 years. The effects of these modifications on the meander morphodynamics are then investigated by means of a 3‐D numerical model, and results are compared to modern and historical field data spanning more than one century. We show that under asymmetric tidal flows, tidal meanders develop depositional patterns according to the dominant flow direction, similar to that of fluvial meanders. In addition, the morphological effects of the nondominant tidal flow become increasingly negligible as tidal flow asymmetry increases. We also show that enhanced sediment and water fluxes from major lateral tributaries, sourced from wind‐wave exposed tidal flats, can critically influence the development of erosional and depositional patterns within tidal meanders otherwise sheltered from wind action by the presence of salt marshes.
Which Orographic Scales Matter Most for Medium‐Range Forecast Skill in the Northern Hemisphere Winter?
Authors: Kanehama Takafumi , Sandu Irina , Beljaars Anton , van Niekerk Annelize , Lott François
Published: November 2019

It is generally accepted that increased horizontal resolution improves the representation of atmospheric circulation in global weather and climate models. Understanding which processes contribute toward this improvement can help to focus future model development efforts. In this study, a set of 10‐day global weather forecasts, performed with different atmospheric and orographic resolutions ranging from 180 to 9 km, are used to examine the impacts of resolving increasingly smaller orographic scales on the forecast skill of the Northern Hemisphere winter circulation. These experiments aim to answer two main questions: What is the relative contribution from increases in atmospheric versus orographic resolution to the overall improvement in the Northern Hemisphere winter medium‐range forecast skill obtained when increasing the horizontal resolution? and How do different orographic scales affect different scales of the atmospheric flow? For experiments in which the subgrid‐scale orography parametrizations are turned off, increases in orographic resolution are responsible for almost all of the increase in skill within the troposphere. In the stratosphere, higher atmospheric resolution also contributes to skill improvements, likely due to a better representation of gravity wave propagation and breaking. All scales of orography considered here are found to be important for the obtained changes in the circulation and appear to rapidly affect all considered scales of the flow. In experiments in which the subgrid‐scale orography parametrizations are turned on, the benefits of increasing the horizontal resolution decrease, but do not entirely disappear, suggesting that these parametrizations are not perfect substitutes for the unresolved orography.
Febuxostat, a Xanthine Oxidoreductase Inhibitor, Decreases NLRP3-dependent Inflammation in Macrophages by Activating the Purine Salvage Pathway and Restoring Cellular Bioenergetics
Authors: Nomura Johji , Kobayashi Tsunefumi , So Alexander , Busso Nathalie
Published: November 2019

The nucleotide-binding oligomerization domain–like receptor family, pyrin domain–containing 3 (NLRP3) inflammasome mediates caspase-1 activation and IL-1β processing and is implicated in autoinflammatory as well as other chronic inflammatory diseases. Recent studies have demonstrated that xanthine oxidoreductase (XOR) inhibition attenuated IL-1β secretion in activated macrophages, but the detailed mechanism of inhibition remains unclear. In this study, we report that febuxostat, an inhibitor of XOR, suppressed NLRP3 inflammasome-mediated IL-1β secretion and cell death by two mechanisms: in a mitochondrial ROS (mitoROS)-dependent and mitoROS-independent manner. MitoROS-independent effects of febuxostat were mediated by an increase of intracellular ATP and improved mitochondrial energetics via the activation of purine salvage pathway. Our findings suggest that cellular bioenergetics are important in regulating NLRP3 activation, and XOR inhibition may be clinically relevant in NLRP3-related inflammatory diseases.
Shape-memory poly(arylene ether ketone)s with tunable transition temperatures and their composite actuators capable of electric-triggered deformation
Authors: Yang Shuai , He Yang , Liu Yanju , Leng Jinsong
Published: November 2019

By means of molecular design and fillers incorporation, PAEK SMPs with tunable transition temperatures were obtained and their composites with electric-triggered SME were fabricated.
Inflection point in the power spectrum of stellar brightness variations
Authors: Shapiro A. I. , Amazo-Gómez E. M. , Krivova N. A. , Solanki S. K.
Published: November 2019

Context. Considerable effort has gone into using light curves observed by such space telescopes as CoRoT, Kepler, and TESS for determining stellar rotation periods. While rotation periods of active stars can be reliably determined, the light curves of many older and less active stars, such as stars that are similar to the Sun, are quite irregular. This hampers the determination of their rotation periods.

Aims. We aim to examine the factors causing these irregularities in stellar brightness variations and to develop a method for determining rotation periods for low-activity stars with irregular light curves.

Methods. We extended the Spectral And Total Irradiance Reconstruction approach for modeling solar brightness variations to Sun-like stars. We calculated the power spectra of stellar brightness variations for various combinations of parameters that define the surface configuration and evolution of stellar magnetic features.

Results. The short lifetime of spots in comparison to the stellar rotation period, as well as the interplay between spot and facular contributions to brightness variations of stars with near solar activity, cause irregularities in their light curves. The power spectra of such stars often lack a peak associated with the rotation period. Nevertheless, the rotation period can still be determined by measuring the period where the concavity of the power spectrum plotted in the log–log scale changes its sign, that is, by identifying the position of the inflection point.

Conclusions. The inflection point of the (log–log) power spectrum is found to be a new diagnostic for stellar rotation periods which is shown to work even in cases where the power spectrum shows no peak at the rotation rate.
A Visible Light Photoredox Catalysed Radical Pictet-Spengler Reaction
Authors: Seehamongkol Theerada , Horngren Tyra H. , Alhajji Mohammed A. M. , Almond-Thynne Joshua , Czyz Milena L. , Barrett Anthony J. , Polyzos Anastasios
Published: November 2019

A methodology for a radical Pictet–Spengler reaction promoted by visible light photoredox catalysis is described. This strategy furnishes tetrahydroisoquinoline derivatives bearing electron poor and electron rich substituents. The reaction proceeds at room temperature and with excellent regioselectivity for the 6-endo intramolecular cyclisation. This radical approach provides a complementary method for the synthesis of the tetrahydroisoquinoline scaffold with substitution patterns inaccessible via established thermal transformations.
Home medicines reviews: a qualitative study of GPs' experiences
Authors: Weir Kristie Rebecca , Naganathan Vasi , Rigby Debbie , McCaffery Kirsten , Bonner Carissa , Trevena Lyndal , McLachlan Andrew J. , Jansen Jesse
Published: November 2019

This qualitative study explored GPs’ experiences with pharmacist-led home medicines reviews (HMRs) and the barriers and facilitators to GPs using HMRs to optimise medicines for older people. Semi-structured interviews were conducted with 32 GPs Australia-wide. Purposeful sampling was undertaken to obtain a representative group in terms of age, gender and location. Data were analysed using framework analysis. Overall, GPs found HMRs useful for educating patients about their medicines, improving adherence and understanding the patient’s home environment. Barriers to effective use of HMRs included patient resistance to having medicines reviewed and limited access to HMRs in regional or rural areas. GPs differed in the extent and way they use HMRs. One group found HMRs very useful, wanted more access to HMRs and reported frequent interactions with pharmacists. A second group was ambivalent, and perceived HMRs could be useful but had limitations in what they can achieve. A third group was sceptical, and reported HMRs rarely provide new insights, and recommendations were not clinically relevant to patients. Understanding GPs’ expectations and preferences through interprofessional communication and partnerships are ways to address these barriers. Future improvements to the HMR program may include incentives and resources that promote collaboration between GPs and pharmacists.
Primary healthcare providers' attitudes and beliefs about the menopause-related care needs of women who have migrated from low- and middle-income countries to Australia
Authors: Stanzel Karin A. , Hammarberg Karin , Fisher Jane
Published: November 2019

Health behaviour during midlife is linked to health outcomes in older age. Primary healthcare providers (PHCPs) are ideally placed to provide health-promoting information opportunistically to women in midlife. The aim of this study was to explore PHCPs views about the menopause-related care needs of migrant women from low- and middle-income countries and what they perceive as barriers and enablers for providing this. Of the 139 PHCPs who responded to an anonymous online survey, less than one-third (29.9%) routinely offered menopause-related information during consultations with migrant women. Most agreed that short appointments times (70.8%), lack of culturally and linguistically appropriate menopause information (82.5%) and lack of confidence in providing menopause-related care (32.5%) are barriers for providing comprehensive menopause-related care to migrant women. To overcome these, a menopause-specific Medicare item number and a one-stop website with health information in community languages were suggested. These findings suggest that menopause-related care is not routinely offered by PHCPs to migrant women from low- and middle- income countries and that their capacity to do this may be improved with adequate educational and structural support.
Learning from the Early Confucians
Authors: Stalnaker Aaron
Published: November 2019

The concluding chapter addresses what contemporary people might learn from the early Confucians about the study’s themes. It argues that moral autonomy is the core of personal autonomy, and that both require training and support to exercise. Furthermore, we should learn to embrace many forms of our dependence on each other as not only inevitable but usually also healthy and good, if society is reasonably well ordered. This has important implications for education, welfare policy, jobs policy, and other areas of government action. A contemporary quasi-Confucian approach to these issues would likely argue for “sufficientarian” government that actively supports family life and work, rather than negative liberty alone. We should also rethink narrow conceptions of expertise, and recognize the sort of generalized human mastery or virtue (autonomy in a broad sense) that directs and makes possible specialized forms of expertise.
The emperor and the dissenters
Authors: Kahlos Maijastina
Published: November 2019

This chapter discusses the imperial power discourse in relation to religious dissidents. Imperial authority was reinforced with the rhetoric of public welfare. The well-being of the empire was thought to be based on the maintenance of good relations with the divine. Consequently, religious unity and the correct form of religion were presented as a matter of state security, and the emperor was put forth as the guardian of the correct religion. In the Christian Empire, Christianity was considered the instrument that protected humankind, and it was the responsibility of the emperor to guarantee the correct interpretation of the nature of God. Thus, imperial power was intrinsically linked with the unity and harmony of Christianity. Accordingly, the very presence of religious dissident groups was taken as an offense to Christian unity and the emperors.
Rhetoric and realities of magic
Authors: Kahlos Maijastina
Published: November 2019

In Late Antiquity, the label of ‘magic’ functioned as a boundary marker between what was understood as the proper religion and the deviant one. It was used in marginalizing and alienating people. This chapter looks at the consequences that the label of magic had for group relations in Late Antiquity. Magic was a discursive category of social disapproval, and it proved to be a powerful cultural weapon against religious dissenters. Religious groups that fell outside the public religion were at risk of being charged with practising magic. In the Christian Empire, these fears were faced by adherents of pagan cults and deviant Christians. Even though there were probably not great numbers of criminal proceedings concerning magic, from time to time the label was employed against political and ecclesiastical rivals. Being suspected of magic was by no means a harmless affair.
Lessons Learned: How Studying Cochlear Implantation Reveals the Context in Which d/Deaf Identities Are Formed
Authors: Mauldin Laura
Published: November 2019

With the exponential increase in the use of cochlear implants, much has been written about how cochlear implants may have changed deaf identities. Recent research documents a trend toward a more hearing-oriented identity with potential for positive psychological well-being. In this chapter, a hearing sociologist and ethnographic researcher highlights how the clinical context shapes both parental decision making about obtaining cochlear implants for their deaf children and the far-reaching influence that hearing-oriented systems have on this decision-making process for parents, deaf individuals, and deaf communities. The author describes the nature of these hearing-oriented systems and highlights issues related to race, ethnicity, and socioeconomic status for cochlear-implanted children. The potential implications for these children are considered. There is a need for research that broadly examines the question of whether and how cochlear implants change the long history of narratives of finding one’s Deaf identity.
Frege on the Real Numbers
Authors: Snyder Eric , Shapiro Stewart
Published: November 2019

This paper is concerned with Gottlob Frege’s theory of the real numbers as sketched in the second volume of his masterpiece Grundgesetze der Arithmetik. It is perhaps unsurprising that Frege’s theory of the real numbers is intimately intertwined with and largely motivated by his metaphysics. The account raises interesting, and surprisingly underexplored, questions about Frege’s metaphysics: Can this metaphysics even accommodate mass quantities like water, gold, light intensity, or charge? Frege’s main complaint with his contemporaries Cantor and Dedekind is that their theories of the real numbers do not build the applicability of the real numbers directly into the construction. In taking Cantor and Dedekind’s Arithmetic theories to be insufficient, clearly Frege takes it to be a desideratum on a theory of the real numbers that their applicability be essential to their construction. We begin with a detailed review of Frege’s theory, one that mirrors Frege’s exposition in structure. This is followed by a critique, outlining Frege’s linguistic motivation for ontologically distinguishing the cardinal numbers from the real numbers. We briefly consider how Frege’s metaphysics might need to be developed, or amended, to accommodate some of the problems. Finally, we offer a detailed examination of Frege’s Application Constraint – that the reals ought to have their applicability built directly into their characterization. It bears on deeper questions concerning the relationship between sophisticated mathematical theories and their applications.
James Harrington
Authors: Hammersley Rachel
Published: November 2019

James Harrington was a significant political and intellectual figure of the mid-seventeenth century, whose life and works embody the complex and contested web of political, religious and cultural ideas that lay at the heart of the English Revolution. His innovative constitutional proposals exercised a profound influence on political debate during that period and for at least two centuries thereafter, and his insights - particularly on democracy - remain relevant today. The complexity of Harrington’s thought has been under-appreciated by scholars in recent years due to the tendency to view him solely from the perspective of republicanism. While research into English republicanism has enriched accounts of seventeenth-century England and the history of political thought, it has also narrowed and obscured our perspective on Harrington. This book offers a broader account of Harrington’s life and work. It addresses Harrington’s contributions to the parliamentary cause and his role as the English agent of Charles I’s nephew, the Prince Elector Palatine. It takes seriously Harrington’s role as a literary figure and his engagement with historical, religious, scientific, and philosophical debates. It puts the case for Harrington as a radical political thinker, committed to democracy and social mobility. It also shows that in a variety of areas he deliberately pursued a middle path, or a balance, between different positions so as to promote reconciliation among a variety of groups. The broader view of Harrington offered here has implications both for our understanding of the seventeenth century and for the discipline of intellectual history.
Quantificational cycles and shifts
Authors: Moreno Mitrović
Published: November 2019

The chapter reports an inter-genetic diachronic study of quantificational particles, drawing from Indo-European and Japonic and making a case for diachronic typological approach to the syntax/semantics/pragmatics of quantificational meanings motivating a treatment of unidirectional semi- or fully cyclical change. Empirically, the quantificational expressions under investigation conform to the bimorphemic expression that comprises a wh-stem and a quantification particle (dubbed ‘superparticle’), e.g. *kwe in Proto-IE, and mo in Old Japanese. The grammaticalization of scalar universal quantifiers into negative polarity items (NPIs) in the history of Japonic is presented using a single feature-system change. What is more, the same feature system is assumed to underlie the aetiology of the ‘quantifier split’ in Indo-European. Theoretically, to present the fully explanatory view of the quantificational shifts and cycles, a novel model of a syntactico-centric pragmatics of grammaticized implicatures (Chierchia et al., 2012; Chierchia, 2013) is assumed.
French negation, the Superset Principle, and Feature Conservation
Authors: De Clercq Karen
Published: November 2019

This chapter provides a nanosyntactic account of negation in French, modelling the change from le bon usage French (BUF) to colloquial French (CF). It is argued that language change is driven by Feature Conservation: the lexical items involved in the expression of sentential negation may change over time, but the features needed remain stable. Furthermore, it is argued that the change from BUF to CF is economy-driven, resulting in bigger lexically stored trees, less spell-out-driven movements and a maximal operationalization of the Superset Principle. In addition, the account shows how negative concord and double negation can be explained as a natural consequence of the interplay of the internal structure of lexical trees and the Superset Principle. Finally, the chapter adds to theoretical discussions within nanosyntax by presenting how the interaction between syntactic movement and spell-out-driven movement may be conceived of.
Changes in the argument and event structure of psych verbs in the history of Spanish
Authors: Batllori Montserrat , Gibert-Sotelo Elisabeth , Pujol Isabel
Published: November 2019

This chapter offers a detailed study of changes affecting the argument structure of Spanish psych verbs that appear with a dative experiencer (EXP). After proposing a three-way classification of these verbs based on their etymological origin, the chapter traces two parallel, but interconnected, diachronic paths: the first one involves the development from transitive (or pronominal) to unaccusative constructions with a dative EXP, whereas the second one concerns the evolution from dynamic to stative events. The use and decrease of the passive in Classical Spanish is also shown to play a role in this change: to wit, passive and unaccusative structures with a dative EXP are structurally similar, as the prepositional agent phrase and the dative EXP originate in the same position.
Victory
Authors: O'Driscoll Cian
Published: November 2019

Victory has historically been regarded as the ‘telos’ or ‘very object’ of war. As one well-placed commentator has noted, war is all about winning. It is baffling to note, then, that contemporary just war theory, the predominant framework for addressing the moral and legal questions that war raises, does not engage the discourse of victory. Today’s just war theorists shun the language of victory, preferring instead to speak about the ‘endings’ of warfare. This book investigates why just war theorists have been so reluctant to speak about victory. It identifies seven principal objections to invoking victory in just war theory and subjects them to cross-examination. It concludes that while there are good reasons for regarding victory as a problematic concept, these same reasons could (and arguably should) be taken as an argument for embracing rather than ignoring victory within the just war framework. Such a move would not only spare just war theory of the charge of irrelevance by ensuring that it remains connected to the pointy end of warfare, it would also illuminate the tragic character of just war itself, revealing both its necessity and limitations.
The Smell of Napalm in the Morning
Authors: O'Driscoll Cian
Published: November 2019

The third problem that victory poses for just war theorists arises from the view that it is a part of the strategic rather than normative vocabulary of war. To the degree that victory is a function of might rather than right, the argument goes, just war theorists have no business engaging it. This chapter examines this contention. It reveals that the idea that victory is an amoral category is out of step with how victory has been conceived down the centuries. From classical times to the present day, victory has always been regarded as a concept that is freighted with ethical and even divine overtones. My purpose in highlighting this is to draw attention to what it reveals about the idea of just war: namely, how it is prone to seed a dangerous combination of complacency and self-righteousness in those who invoke it.