bluuebunny/crossref_metadata_2025 huggingface dataset:
A tight-coupling scheme sharing minimum information across a spatial interface between gyrokinetic turbulence codes
Authors: Dominski J. , Ku S. , Chang C.-S. , Choi J. , Suchyta E. , Parker S. , Klasky S. , Bhattacharjee A.
Published: July 2018

A new scheme that tightly couples kinetic turbulence codes across a spatial interface is introduced. This scheme evolves from considerations of competing strategies and down-selection. It is found that the use of a composite kinetic distribution function and fields with global boundary conditions as if the coupled code were one makes the coupling problem tractable. In contrast, coupling the two solutions from each code across the overlap region is found to be more difficult due to numerical dephasing of the turbulent solutions between two solvers. Another advantage of the new scheme is that the data movement can be limited to the 3D fluid quantities, instead of higher dimensional kinetic information, which is computationally more efficient for large scale simulations on leadership class computers.
Can Popular DFT Approximations and Truncated Coupled Cluster Theory Describe the Potential Energy Surface of the Beryllium Dimer?
Authors: Karton Amir , McKemmish Laura K.
Published: July 2018

The potential energy surface (PES) of the ground state of the beryllium dimer poses a significant challenge for high-level ab initio electronic structure methods. Here, we present a systematic study of basis set effects over the entire PES of Be2 calculated at the full configuration interaction (FCI) level. The reference PES is calculated at the valence FCI/cc-pV{5,6}Z level of theory. We find that the FCI/cc-pV{T,Q}Z basis set extrapolation reproduces the shape of the FCI/cc-pV{5,6}Z PES as well as the binding energy and vibrational transition frequencies to within ~10 cm−1. We also use the FCI/cc-pV{5,6}Z PES to evaluate the performance of truncated coupled cluster methods (CCSD, CCSD(T), CCSDT, and CCSDT(Q)) and contemporary density functional theory methods (DFT) methods for the entire PES of Be2. Of the truncated coupled cluster methods, CCSDT(Q)/cc-pV{5,6}Z provides a good representation of the FCI/cc-pV{5,6}Z PES. The GGA functionals, as well as the HGGA and HMGGA functionals with low percentages of exact exchange tend to severely overbind the Be2 dimer, whereas BH&HLYP and M06-HF tend to underbind it. Range-separated DFT functionals tend to underbind the dimer. Double-hybrid DFT functionals show surprisingly good performance, with DSD-PBEP86 being the best performer. Møller–Plesset perturbation theory converges smoothly up to fourth order; however, fifth-order corrections have practically no effect on the PES.
Thermo-responsive ion imprinted polymer on the surface of magnetic carbon microspheres for identification and removal of low-concentrations of Cu2+
Authors: Liu Weifeng , Qin Lei , An Zhuolin , Chen Lin , Liu Xuguang , Yang Yongzhen , Xu Bingshe
Published: July 2018

Environmental contextBecause of the multiple industrial applications of metals, contamination by metal ions is widespread and can at times endanger the environment and the health of human beings. We prepared ion-imprinted adsorbents to achieve selective recognition and smart separation of low-concentrations of copper ions from water. These smart imprinted materials have high potential for selective adsorption and removal of contaminant copper ions, particularly at very low concentrations.
AbstractA temperature-responsive magnetic adsorbent (poly(N-propyl acrylamide) grafted magnetic carbon microspheres, Cu2+-IIP) was synthesised by ion imprinting technology for low concentration Cu2+ removal. Cu2+-IIP was prepared by using N-propyl acrylamide as a thermo-sensitive functional monomer, N,N-methylene-bis-acrylamide as a cross-linker and ammonium persulfate as an initiator. The morphologies and microstructures of samples were characterised by transmission electron microscopy, Fourier transform infrared spectrometry, thermogravimetry and vibrating sample magnetometry. Adsorption experiments were conducted in terms of kinetics, isotherms and selective recognition adsorption at low feed concentrations. Results indicate that Cu2+-IIP possesses good recognition selectivity and affinity for Cu2+, and can be separated from the treated solution quickly by applying an external magnetic field. The adsorption capacity towards Cu2+ depends on temperature and reaches a maximum value of 45.46 mg g−1 at 35 °C, higher than that of the non-imprinted polymer. The adsorption behaviour of Cu2+ on Cu2+-IIP can be well defined with both the pseudo-second-order kinetic model and Langmuir isotherm model. Cu2+-IIP performs good adsorption selectivity towards Cu2+ because the relative selectivity factors of Cu2+ with respect to Ni2+, Zn2+ and Cd2+ are 7.14, 7.60 and 6.77, respectively. The adsorption capacity of Cu2+-IIP remained 88.41 % after five cycles.
Foam-driven fracture
Authors: Lai Ching-Yao , Rallabandi Bhargav , Perazzo Antonio , Zheng Zhong , Smiddy Samuel E. , Stone Howard A.
Published: July 2018

Significance

Hydraulic fracturing plays an important role in meeting today’s energy demands. However, the substantial use of fresh water in fracturing and wastewater returning to the surface pose risks to the environment. Alternative technology has been developed that reduces the water-related risks by injecting aqueous foam instead of water to fracture shale formations, but the mechanism is poorly understood. Here, we show, using laboratory experiments, that the injection of foam instead of water dramatically changes the fracture dynamics when the foam compressibility is important. We develop a scaling argument for the fracture dynamics that exhibits excellent agreement with the experimental results. Our findings extend to other systems involving compressible foams, including fire-fighting, energy storage using compressed foams, and enhanced oil recovery.
Plant pathogen effector utilizes host susceptibility factor NRL1 to degrade the immune regulator SWAP70
Authors: He Qin , Naqvi Shaista , McLellan Hazel , Boevink Petra C. , Champouret Nicolas , Hein Ingo , Birch Paul R. J.
Published: July 2018

Significance

Plant pathogens, such as the infamous potato blight agent
Phytophthora infestans
, deliver effectors inside living plant cells to promote disease. Recent evidence suggests that some effectors will associate with endogenous negative regulators of immunity, or so-called susceptibility (S) factors, inside living plant cells. To date, little is known about how effectors exploit S factors to inactivate the immune system. We discovered that
P. infestans
effector Pi02860 uses the potato StNRL1 protein as an S factor by promoting its ability to target a positive regulator of immunity, StSWAP70, for proteasome-mediated degradation. Our results reveal that protecting StSWAP70 from degradation by reducing the activity or availability of NRL1 provides a means to attenuate late blight disease.
Teachers’ curriculum agency in teaching a standards‐based curriculum
Authors: Alvunger Daniel
Published: July 2018

In 2011, Sweden introduced explicit standards for the curriculum used in compulsory schooling through the implementation of ‘knowledge requirements’ that align content, abilities and assessment criteria. This article explores and analyses social science teachers’ curriculum agency through a theoretical framework comprised of ‘teacher agency’ and Bernstein's concepts of ‘pedagogic device’, ‘hierarchical knowledge structure’ and ‘horizontal knowledge structure’. Teachers’ curriculum agency, in recontextualisation of the curriculum, is described and understood through three different ‘spaces’: a collective space, an individual space and an interactive space in the classroom. The curriculum and time are important for the possibilities of agency – the teachers state that the new knowledge requirements compel them to include and assess a lot of content in each ‘curriculum task’. It is possible to identify a recontextualisation process of ‘borrowing’ and combining content from curriculum tasks across the different subjects. This process is explained by the horizontal knowledge structure and ‘weak grammar’ of the social sciences. Abilities, on the other hand, stand out as elements of a hierarchical knowledge structure in which a discursive space is opened for knowledge to transcend contexts and provides opportunities for meaning‐making. The space gives teachers room for action and for integrating disciplinary content.
ICAM-1 controls development and function of ILC2
Authors: Lei Ai-Hua , Xiao Qiang , Liu Gao-Yu , Shi Kun , Yang Qiong , Li Xing , Liu Yu-Feng , Wang Hai-Kun , Cai Wei-Ping , Guan Yu-Juan , Gabrilovich Dmitry I. , Zhou Jie
Published: July 2018

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1–deficient (ICAM-1−/−) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1−/− mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1−/− mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.
Poverty: A Very Short Introduction
Authors: Jefferson Philip N.
Published: July 2018

Millions of people worldwide live in poverty. Why is that? What has been done about it in the past? And what is being done about it now? Poverty: A Very Short Introduction explores how the answers to these questions lie in the social, political, economic, educational, and technological processes that impact all of us throughout our lives—from the circumstances of birth and gender to access to clean water and whether it is wartime or peacetime. The degree of vulnerability is all that differentiates us. This VSI looks at the history of poverty, the practical and analytical efforts made to eradicate it, and the prospects for further poverty alleviation in the future.
6. Distribution and mobility
Authors: Jefferson Philip N.
Published: July 2018

We all start out in a given position in society and with a level of income (or wealth). What determines where we will end up? Will we be better off than our parents were? For people living in poverty, the ease or difficulty of movement across the income distribution of society is the difference between hope and despair. If movement is easy, society is seen as being fluid—a dynamic place to live and raise a family. If movement is difficult, society is seen as being rigid. This movement is measured in quintiles of the income distribution. ‘Distribution and mobility’ considers the distribution of income, lifetime mobility, poverty transitions, intergenerational mobility, and poverty traps.
The Holy Roman Empire: A Very Short Introduction
Authors: Whaley Joachim
Published: July 2018

The Holy Roman Empire: A Very Short Introduction outlines the fascinating thousand-year history of the Holy Roman Empire from 800 to 1806, and its legacy for the two centuries after its dissolution. Founded on the basis of Charlemagne’s Frankish kingdom, its imperial title went to the German monarchy that became established in the 9th and 10th centuries. They claimed Charlemagne’s legacy, including his role as protector of the papacy and guardian of the Church. Throughout its lifetime, the empire’s growth and history was shaped by the major developments in Europe, from the Reformation to the French revolutionary wars. The legal traditions established by the empire have shaped the history of German-speaking Europe ever since.
Introduction
Authors: Whaley Joachim
Published: July 2018

The Holy Roman Empire of the German Nation was founded in 800 with the coronation of Charlemagne as emperor by the pope, and was dissolved in 1806. ‘What was the Holy Roman Empire?’ explains that the original Frankish kingdom was a tribal society that followed an elected leader. On this foundation subsequent ruling dynasties developed what became a fully fledged feudal system. From the middle of the 14th century, the empire developed institutional and legal structures that ultimately became more important than the feudal relationship between the emperor and his vassals. The territories of the empire and its imperial coronations and insignia are described.
1. Roman Empire and German kingdom
Authors: Whaley Joachim
Published: July 2018

‘Roman Empire and German kingdom: from Charlemagne to the Ottonians’ describes the period of time after the decline of the Roman Empire and the establishment of the Germanic tribes of the Franks on its north-western periphery through to the reign of Henry of Bavaria, whose death in 1024 ended the Ottonian dynasty. Charlemagne’s reign and the Carolingians are described, followed by the eastern kingdom of the Franks, which under the rule of the sons of Louis the German (r. 843–76) developed a distinct sense of identity. The Saxon-German kingdom; the kingdom of Italy; Otto I’s imperial rule in Germany; and the new aspirations of Otto II and Otto III are also outlined.
4. The early modern empire (1)
Authors: Whaley Joachim
Published: July 2018

‘The early modern empire (1): from Maximilian I to the Thirty Years War’ outlines the period from 1493 to 1648. Maximilian I’s reign (1493–1519) transformed the empire. It remained a feudal society, in which the princes owed allegiance to the emperor, but it now gained more elements of a written constitution. Subsequently, the empire acquired a more extensive body of constitutional law than any other early modern European monarchy. The reigns of Charles V, Ferdinand I, and Maximilian II, and key events including Martin Luther’s Reformation movement, the Peace of Augsburg in 1555, and the Thirty Years War (1618–48) that started with a Bohemian rebellion against Habsburg rule, are all described.
Ethics
Authors: Inwood Brad
Published: July 2018

Ethics is the part of the Stoics’ legacy that is most prominent and influential today. Their theory of the good life for human beings falls into the family of theories associated with Socrates and his followers. This tradition includes Plato and most Platonists, Xenophon, the Cynics, Aristotle, and later Aristotelians, all of whom share the view that virtue, the excellence of a human being, is the highest value and is its own reward. ‘Ethics’ discusses the Stoics’ views on human nature and rationality; the four basic virtues: justice, courage, wisdom, and moderation or self-control; and the doctrine that the fully rational and wise person will be free of passions.
2. How synthetic biology is done
Authors: Davies Jamie A.
Published: July 2018

Synthetic biology depends on technologies for reading and writing DNA sequences of genes. Modification is almost always done at the genetic level because genes are heritable, needing to be engineered only once. ‘How synthetic biology is done’ describes the processes of sequencing DNA and DNA synthesis. Sequencing DNA is important for two main reasons: to analyse natural genes and natural gene-controlling regions of DNA; and to verify the correctness of DNA we have tried to write. The design of synthetic constructs is also considered along with the use of synthetic biology libraries; how the synthetic system is loaded into a living cell; and the potential issues of cross-talk and orthogonality.
5. Synthetic biology for engineering
Authors: Davies Jamie A.
Published: July 2018

While it may be expected that medicine and chemistry will have potential uses for synthetic biology, it is less obvious that the field might be relevant to the inorganic engineering of buildings, bridges, and computers. Nevertheless, the responsiveness of biological systems and tiny scale of their constituent molecules do have the potential to solve major problems (and perhaps create some new ones). ‘Synthetic biology for engineering’ focuses on three aspects of the use of synthetic biology in modern engineering: construction, computing, and communication. It discusses the use of bacteria spores to ‘heal’ cracks in concrete; data storage in DNA; DNA-based computers; and the use of DNA in cryptography.
2. Geology: the early days
Authors: Zalasiewicz Jan
Published: July 2018

‘Geology: the early days’ provides a brief history of ideas on the Earth and its processes. Among the earliest recorded scientific speculations on the Earth were those of the ancient Greeks, such as Anaximander of Miletus and Pythagoras. Other cultures that independently developed ideas include the Vedic Period of India (c.1300–300 bc) and the Song Dynasty of China (960–1279 ad). Huge strides were made during the Enlightenment period, and the key contributions of figures such as Georges-Louis Leclerc, Comte de Buffon, James Hutton, Baron Georges Cuvier, Mary Anning, William Buckland, Charles Lyell, Abraham Gottlob Werner, and Adam Sedgwick are discussed, with the creation of the Geological Time Scale.
3. Modern breakthroughs and revolutions
Authors: Zalasiewicz Jan
Published: July 2018

The early geologists built a detailed relative history of the Earth, much of which holds true today, but they had no idea of how long that history was in years. ‘Modern breakthroughs and revolutions’ explains that the ability to measure Earth time transformed geology. With the discovery of radioactivity in 1896, radiometric dating of rocks became a possibility. This numerical dating, when combined with the relative dating provided by fossils, provided a means to calibrate the long and eventful history of our planet. The study of ocean floor geology and the birth of the revolutionary plate tectonics concept explained the patterns of mountain ranges, volcanism, and earthquakes.
Is What You Put in What You Get Out? —Textbook-derived Lexical Bundle Processing in Beginner English Learners
Authors: Northbrook Julian , Conklin Kathy
Published: July 2018

Usage-based approaches to second language acquisition put a premium on the linguistic input that learners receive and predict that any sequences of words that learners encounter frequently will experience a processing advantage. The current study explores the processing of high-frequency sequences of words known as ‘lexical bundles' in beginner learners of English in Japanese secondary school. To do this we use a phrasal judgment task, testing students on items taken directly from their teaching materials. Students responded to lexical bundles that occurred in their textbooks significantly faster and more accurately compared with non-lexical bundles, and were sensitive to the frequency of occurrence in their textbooks. This study shows, perhaps for the first time, that even very low-level, beginner secondary students are sensitive to the frequency of lexical bundles which appear in the input they receive from teaching materials, a finding that has important implications for teaching and material design.
DiscoverSL: an R package for multi-omic data driven prediction of synthetic lethality in cancers
Authors: Das Shaoli , Deng Xiang , Camphausen Kevin , Shankavaram Uma
Published: July 2018

Synthetic lethality is a state when simultaneous loss of two genes is lethal to a cancer cell, while the loss of the individual genes is not. We developed an R package DiscoverSL to predict and visualize synthetic lethality in cancers using multi-omic cancer data. Mutation, copy number alteration and gene expression data from The Cancer Genome Atlas project were combined to develop a multi-parametric Random Forest classifier. The effects of selectively targeting the predicted synthetic lethal genes is tested in silico using shRNA and drug screening data from cancer cell line databases. The clinical outcome in patients with mutation in primary gene and over/under-expression in the synthetic lethal gene is evaluated using Kaplan–Meier analysis. The method helps to identify new therapeutic approaches by exploiting the concept of synthetic lethality.

Availability and implementation

DiscoverSL package with user manual and sample workflow is available for download from github url: https://github.com/shaoli86/DiscoverSL/releases/tag/V1.0 under GNU GPL-3.

Supplementary information

Supplementary data are available at Bioinformatics online.
A Seat at the Table: The Positioning of Families During Care Conferences in Nursing Homes
Authors: Puurveen Gloria , Cooke Heather , Gill Rupali , Baumbusch Jennifer
Published: July 2018

Background and Objectives

Current nursing home policy emphasizes the need for collaborative, team-based care planning in which families and/or residents are actively involved. Resident care conferences are common where care providers, families, and/or residents discuss and coordinate resident care needs and evaluate care goals. This study critically examines the process, structure, and content of care conferences to expand our understanding of how resident care is negotiated among care providers and families in this context.

Research Design and Methods

This study was part of a larger critical ethnography examining the negotiation of care work among care providers, families, and residents in three purposively selected nursing homes in British Columbia, Canada. Thirty-seven care conferences were observed. Field notes and interview data were thematically analyzed with a focus on what was said, who said what and to whom, whose voice was privileged, and how power manifested between care providers, families, and/or residents.

Results

As illustrated by three key themes, Exclusion by Process—Following Script, Exclusion by Content—Scripted Reports, and Exclusion through Devalued Knowledge, families were overtly and covertly excluded from contributing to the care conferences. As such, families’ presence did not guarantee open communication or active solicitation of their perspectives.

Discussion and Implications

The use of predetermined agendas and processes, clinically generic reporting, and technical jargon reproduced the structural inequality between care providers and families making collaboration difficult to effectively negotiate. For care conferences to meaningfully contribute to person-centered care, it is imperative that mutual exchange be promoted and families empowered to participate as equals.
By-catch in no-fed aquaculture: exploiting mussel seed persistently and extensively disturbs the accompanying assemblage
Authors: Piñeiro-Corbeira Cristina , Barrientos Sara , Olmedo Mercedes , Cremades Javier , Barreiro Rodolfo
Published: July 2018

Although aquaculture sometimes lessens the negative effects of fishing by lowering the need to capture wild animals and plants, some aquaculture practices still require the exploitation of wild populations. A largely overlooked case is the use of wild populations to provide seed to sea farms. Mussel farming in Northwest Spain involve the capture of thousands of tons of young mussels (0.5–2 cm long) from the nearby rocky intertidal every year to supply floating rafts. Despite its volume, the impact of this activity on other sessile organisms remains unassessed. To fill this gap in our knowledge, we monthly monitored the sessile intertidal assemblage of five protected and six exploited sites during the closed season in 2016 following a nested sampling plan. Like the by-catch typical of other fisheries, harvesting young mussels for aquaculture was detrimental to the abundance and diversity of the associated sessile assemblage not directly targeted by this activity. Coverage and richness were also significantly lowered by the exploitation of mussel seed, and the community structure of protected and exploited sites was significantly different. These differences continued until the next open season, suggesting that the closed season was too short for the recovery of the associated non-target sessile assemblage. Given the size of the local mussel industry, the incomplete recovery along the closed season implies that mussel aquaculture must be putting a sustained pressure on a sizeable portion of the rocky intertidal of Northwest Spain.
A convergent adaptive finite element method for elliptic Dirichlet boundary control problems
Authors: Gong Wei , Liu Wenbin , Tan Zhiyu , Yan Ningning
Published: July 2018

This paper concerns the adaptive finite element method for elliptic Dirichlet boundary control problems in the energy space. The contribution of this paper is twofold. First, we rigorously derive efficient and reliable a posteriori error estimates for finite element approximations of Dirichlet boundary control problems. As a by-product, a priori error estimates are derived in a simple way by introducing appropriate auxiliary problems and establishing certain norm equivalence. Secondly, for the coupled elliptic partial differential system that resulted from the first-order optimality system, we prove that the sequence of adaptively generated discrete solutions including the control, the state and the adjoint state, guided by our newly derived a posteriori error indicators, converges to the true solution along with the convergence of the error estimators. We give some numerical results to confirm our theoretical findings.
Machine learning for psychiatric patient triaging: an investigation of cascading classifiers
Authors: Singh Vivek Kumar , Shrivastava Utkarsh , Bouayad Lina , Padmanabhan Balaji , Ialynytchev Anna , Schultz Susan K
Published: July 2018

Objective

Develop an approach, One-class-at-a-time, for triaging psychiatric patients using machine learning on textual patient records. Our approach aims to automate the triaging process and reduce expert effort while providing high classification reliability.

Materials and Methods

The One-class-at-a-time approach is a multistage cascading classification technique that achieves higher triage classification accuracy compared to traditional multiclass classifiers through 1) classifying one class at a time (or stage), and 2) identification and application of the highest accuracy classifier at each stage. The approach was evaluated using a unique dataset of 433 psychiatric patient records with a triage class label provided by “I2B2 challenge,” a recent competition in the medical informatics community.

Results

The One-class-at-a-time cascading classifier outperformed state-of-the-art classification techniques with overall classification accuracy of 77% among 4 classes, exceeding accuracies of existing multiclass classifiers. The approach also enabled highly accurate classification of individual classes—the severe and mild with 85% accuracy, moderate with 64% accuracy, and absent with 60% accuracy.

Discussion

The triaging of psychiatric cases is a challenging problem due to the lack of clear guidelines and protocols. Our work presents a machine learning approach using psychiatric records for triaging patients based on their severity condition.

Conclusion

The One-class-at-a-time cascading classifier can be used as a decision aid to reduce triaging effort of physicians and nurses, while providing a unique opportunity to involve experts at each stage to reduce false positive and further improve the system’s accuracy.
Evolving role of genetic testing for the clinical management of autosomal dominant polycystic kidney disease
Authors: Lanktree Matthew B , Iliuta Ioan-Andrei , Haghighi Amirreza , Song Xuewen , Pei York
Published: July 2018

Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by mutations of two genes, PKD1 and PKD2. In the presence of a positive family history of ADPKD, genetic testing is currently seldom indicated as the diagnosis is mostly based on imaging studies using well-established criteria. Moreover, PKD1 mutation screening is technically challenging due to its large size, complexity (i.e. presence of six pseudogenes with high levels of DNA sequence similarity) and extensive allelic heterogeneity. Despite these limitations, recent studies have delineated a strong genotype–phenotype correlation in ADPKD and begun to unravel the role of genetics underlying cases with atypical phenotypes. Furthermore, adaptation of next-generation sequencing (NGS) to clinical PKD genetic testing will provide a high-throughput, accurate and comprehensive screen of multiple cystic disease and modifier genes at a reduced cost. In this review, we discuss the evolving indications of genetic testing in ADPKD and how NGS-based screening promises to yield clinically important prognostic information for both typical as well as unusual genetic (e.g. allelic or genic interactions, somatic mosaicism, cystic kidney disease modifiers) cases to advance personalized medicine in the era of novel therapeutics for ADPKD.
Biomimetic twisted plywood structural materials
Authors: Chen Si-Ming , Gao Huai-Ling , Zhu Yin-Bo , Yao Hong-Bin , Mao Li-Bo , Song Qi-Yun , Xia Jun , Pan Zhao , He Zhen , Wu Heng-An , Yu Shu-Hong
Published: July 2018

Biomimetic designs based on micro/nanoscale manipulation and scalable fabrication are expected to develop new-style strong, tough structural materials. Although the mimicking of nacre-like ‘brick-and-mortar’ structure is well studied, many highly ordered natural architectures comprising 1D micro/nanoscale building blocks still elude imitation owing to the scarcity of efficient manipulation techniques for micro/nanostructural control in practical bulk counterparts. Herein, inspired by natural twisted plywood structures with fascinating damage tolerance, biomimetic bulk materials that closely resemble natural hierarchical structures and toughening mechanisms are successfully fabricated through a programmed and scalable bottom-up assembly strategy. By accurately engineering the arrangement of 1D mineral micro/nanofibers in biopolymer matrix on the multiscale, the resultant composites display optimal mechanical performance, superior to many natural, biomimetic and engineering materials. The design strategy allows for precise micro/nanostructural control at the macroscopic 3D level and can be easily extended to other materials systems, opening up an avenue for many more micro/nanofiber-based biomimetic designs.
Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll‐like receptor 4 signaling pathway
Authors: Zhang Xiangsheng , Lu Yue , Wu Qi , Dai Haibin , Li Wei , Lv Shengyin , Zhou Xiaoming , Zhang Xin , Hang Chunhua , Wang Jian
Published: July 2018

Inflammation plays a key role in the progression of subarachnoid hemorrhage (SAH). Here, we examined the effects of astaxanthin (ATX) on the inflammatory response and secondary damage after SAH and the underlying mechanisms of action. In vivo, a prechiasmatic cistern injection model was established in rats and mice. In addition, neuron‐microglia cocultures were exposed to oxyhemoglobin to mimic SAH in vitro. Western blotting revealed that protein expression of TLR4 was markedly increased in microglia at 24 h after SAH, with consequent increases in the downstream molecules myeloid differentiation factor 88 and NF‐κB. Treatment with ATX significantly inhibited the TLR4 activation, increased sirtuin 1 expression, and inhibited the subsequent inflammatory response both in vivo and in vitro. ATX also significantly decreased high‐mobility group box 1 nuclear translocation and secretion in neurons, an effect that was reversed by the sirtuin 1‐specific inhibitor sirtinol. ATX administered 4 h after SAH ameliorated cerebral inflammation, brain edema, and neuronal death and improved neurologic function. ATX reduced neuronal death but did not improve neurologic function in TLR4 knockout mice. These results suggest that ATX reduces the proinflammatory response and secondary brain injury after SAH, primarily by increasing sirtuin 1 levels and inhibiting the TLR4 signaling pathway.—Zhang, X., Lu, Y., Wu, Q., Dai, H., Li, W., Lv, S., Zhou, X., Zhang, X., Hang, C., Wang, J. Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll‐like receptor 4 signaling pathway. FASEB J. 33, 722–737 (2019). www.fasebj.org
Assessment of Lung Aeration and Recruitment by CT Scan and Ultrasound in Acute Respiratory Distress Syndrome Patients*
Authors: Chiumello Davide , Mongodi Silvia , Algieri Ilaria , Vergani Giordano Luca , Orlando Anita , Via Gabriele , Crimella Francesco , Cressoni Massimo , Mojoli Francesco
Published: July 2018

Objectives:

Lung ultrasound is commonly used to evaluate lung morphology in patients with acute respiratory distress syndrome. Aim of this study was to determine lung ultrasound reliability in assessing lung aeration and positive end-expiratory pressure–induced recruitment compared with CT.

Design:

Randomized crossover study.

Setting:

University hospital ICU.

Patients:

Twenty sedated paralyzed acute respiratory distress syndrome patients: age 56 years (43–72 yr), body mass index 25 kg/m2 (22–27 kg/m2), and Pao
2/Fio
2 160 (113–218).

Interventions:

Lung CT and lung ultrasound examination were performed at positive end-expiratory pressure 5 and 15 cm H2O.

Measurements and Main Results:

Global and regional Lung Ultrasound scores were compared with CT quantitative analysis. Lung recruitment (i.e., decrease in not aerated tissue as assessed with CT) was compared with global Lung Ultrasound score variations. Global Lung Ultrasound score was strongly associated with average lung tissue density at positive end-expiratory pressure 5 (R
2 = 0.78; p < 0.0001) and positive end-expiratory pressure 15 (R
2 = 0.62; p < 0.0001). Regional Lung Ultrasound score strongly correlated with tissue density at positive end-expiratory pressure 5 (r
s = 0.79; p < 0.0001) and positive end-expiratory pressure 15 (r
s = 0.79; p < 0.0001). Each step increase of regional Lung Ultrasound score was associated with significant increase of tissue density (p < 0.005). A substantial agreement was found between regional Lung Ultrasound score and CT classification at positive end-expiratory pressure 5 (k = 0.69 [0.63–0.75]) and at positive end-expiratory pressure 15 (k = 0.70 [0.64–0.75]). At positive end-expiratory pressure 15, both global Lung Ultrasound score (22 [16–27] vs 26 [21–29]; p < 0.0001) and not aerated tissue (42% [25–57%] vs 52% [39–67%]; p < 0.0001) decreased. However, Lung Ultrasound score variations were not associated with lung recruitment (R
2 = 0.01; p = 0.67).

Conclusions:

Lung Ultrasound score is a valid tool to assess regional and global lung aeration. Global Lung Ultrasound score variations should not be used for bedside assessment of positive end-expiratory pressure–induced recruitment.
An LC-MS/MS Method for Absolute Quantification of Nivolumab in Human Plasma: Application to Clinical Therapeutic Drug Monitoring
Authors: Irie Kei , Okada Akira , Yamasaki Yuta , Kokan Chiyuki , Hata Akito , Kaji Reiko , Fukushima Keizo , Sugioka Nobuyuki , Okada Yutaka , Katakami Nobuyuki , Fukushima Shoji
Published: July 2018

Background:

Nivolumab is a fully humanized IgG4 monoclonal antibody that targets the programmed death-1 (PD-1) receptor, disrupting PD-1–mediated signaling and restoring antitumor immunity. The objective of this study was to develop a nivolumab quantification method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to evaluate its application in clinical therapeutic drug monitoring.

Methods:

Nivolumab was purified from human plasma using rProtein A resin and then digested with trypsin. The ASGITFSNSGMHWVR peptide (multiple reaction monitoring transition: m/z 550.6→661.4) was detected as a surrogate peptide of nivolumab by triple quadrupole mass spectrometry. Plasma samples (126) were collected from 14 patients with non–small cell lung cancer who were undergoing clinical dosing regimen with nivolumab. The pharmacokinetic data were analyzed using Phoenix NLME software (Version 7.0, Certara, St. Louis, MO) based on a previously reported population pharmacokinetics (PPK) model of nivolumab.

Results:

Nivolumab was selectively detected in human plasma and the linear range was 5–200 mcg/mL (R2 = 0.99). The accuracy and intraday and interday imprecision were within ±15% of the quality control values of 5 (lower limit of quantification), 10 (low), 80 (medium), and 160 (high) mcg/mL. The nivolumab concentrations measured using LC-MS/MS were consistent with those of previously reported PPK models, and the pharmacokinetic parameters could be adequately predicted from a single trough concentration using a Bayesian approach.

Conclusions:

An absolute quantification method for nivolumab using LC-MS/MS was successfully developed and validated. Combined with PPK analysis, this method should be useful for the therapeutic drug monitoring of nivolumab in clinical practice.
PSEUDOXANTHOMA ELASTICUM: SUCCESSFUL LONG-TERM MANAGEMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO ANGIOID STREAKS WITH PRO RE NATA INTRAVITREAL BEVACIZUMAB INJECTIONS
Authors: Kim Jiyeon , Dalziel David
Published: July 2018

Purpose:

To demonstrate how a patient with recurrent episodes of choroidal neovascularization (CNV), secondary to angioid streaks, can be managed successfully with a pro re nata regime of intravitreal bevacizumab injection over an eight-year period.

Method:

A 32-year-old white woman with pseudoxanthoma elasticum has been followed up over an eight-year period for management of recurrent episodes of CNV in both eyes. She was educated to recognize the early signs and symptoms of CNV. Physical examination including visual acuity and slit-lamp examination as well as investigations such as macula optical coherence tomography and optical coherence tomography angiography were performed. Bevacizumab injections were given to her when she was diagnosed with CNV.

Results:

Multiple episodes of CNV were successfully treated with pro re nata regimes of intravitreal bevacizumab injections. The patient was able to maintain excellent visual acuity of 0 logarithm of the minimum angle of resolution even after suffering recurrent episodes of CNV.

Conclusion:

This case report supports that a pro re nata regime of intravitreal bevacizumab injection therapy can be used successfully to treat recurrent episodes of CNV in a patient with pseudoxanthoma elasticum over an eight-year period. Early diagnosis through patient education and the use of appropriate diagnostic tools such as optical coherence tomography angiography have enabled us to deliver early treatment, resulting in an excellent outcome for this patient.
INTRAVITREAL MELPHALAN FOR TREATMENT OF VITREOUS SEEDING FROM CHOROIDAL MELANOMA
Authors: Masoomian Babak , Mashayekhi Arman , Malik Kunal , Shields Carol L.
Published: July 2018

Purpose:

To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan.

Methods:

Case report.

Results:

A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 μg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications.

Conclusion:

Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.
SUCCESSFUL SURGICAL OUTCOME OF FULL-THICKNESS MACULAR HOLE WITH CHOROIDAL COLOBOMA
Authors: Venkatesh Ramesh , Yadav Naresh Kumar , Sinha Shivani , Mohan Ashwin
Published: July 2018

Purpose:

To report a case of successful closure of macular hole after surgery in a patient with choroidal coloboma.

Methods:

Interventional case report.

Case description:

A 17-year-old boy developed a full-thickness macular hole at the edge of an inferior choroidal coloboma in the right eye. Visual acuity in the right eye was 20/200. Surgical management with 25-G pars plana vitrectomy, internal limiting membrane peeling, and silicone oil tamponade was performed. At 6 weeks after surgery, the macular hole closed with Type 1 closure. After silicone oil removal, the vision in the right eye improved to 20/60.

Conclusion:

Macular hole in the presence of choroidal coloboma is quite uncommon. With better understanding of the etiopathogenesis of macular hole formation and advances in vitreoretinal surgery, it is safe and useful in attempting surgery in these patients.
Efficacy of Trial Fitting and Software Fitting for Orthokeratology Lens: One-Year Follow-Up Study
Authors: Lu Daqian , Gu Tianpu , Lin Weiping , Li Na , Gong Boteng , Wei Ruihua
Published: July 2018

Objective:

To observe and compare the clinical efficacy of 1-year trial fitting and software fitting orthokeratology lenses.

Methods:

One hundred myopes who received vision correction with the use of orthokeratology lenses form July 2016 to September 2017 were included in this study. Subjects were assigned randomly into the two groups: the trial fitting group (group A) and the software fitting group (group B). For the right eye of each subject, measurements, such as uncorrected visual acuity (UCVA, logarithm of minimal angle of resolution), refractive error, corneal topography, ocular health status, and the fitting situation, were obtained at baseline, 1 week, 1 month, 3 months, 6 months, and 12 months after lens wear. Axial length and corneal endothelium cells (CECs) were also measured at baseline and 12 months after wearing the lens.

Results:

Compared with the baseline, the spherical equivalent refraction, UCVA, and central corneal curvature changed significantly after orthokeratology (OK) lens wear (all P<0.05). Between groups A and B, the parameters aforementioned were insignificant at each time point (all P>0.05). Axial length and CECs showed no significant changes during the first year of OK treatment (all P>0.05). Rate of corneal staining between two groups revealed no difference during 1-year visit (P<0.05).

Conclusion:

Both the trial lens fitting and software fitting approaches were effective in temporarily reducing myopia, providing good UCVA and delaying the elongation of axial length for moderate and high myopic adolescents. Both the two approaches can be combined in OK lens fitting.
Visual Outcomes and Prognostic Factors of Successful Penetrating Keratoplasty in 0- to 7-Year-Old Children With Congenital Corneal Opacities
Authors: Lin Qi , Shi Wei , Miao Sen , Zhang Yingnan , Li Li , Pan Zhiqiang
Published: July 2018

Purpose:

To determine the visual acuity and prognostic factors after successful penetrating keratoplasty (PK) in 0 to 7-year-old children with congenital corneal opacities.

Methods:

Sixty eyes (50 patients) with clear grafts after PK for congenital corneal opacity were enrolled and followed for 6 to 82 months. Visual acuity was measured using Teller acuity cards or Snellen charts, and cycloplegic refraction and flash visual-evoked potentials were measured. Mean age at primary keratoplasty was 2.5 ± 1.7 years. The mean follow-up duration was 18.9 ± 19.3 months.

Results:

Ambulatory vision (≥20/960) was achieved in 43 of 60 eyes (71.7%) at last follow-up, and 14 eyes (23.3%) had visual acuities >20/260. Compared with unilateral opacity eyes (58.8%), a significantly higher proportion of bilateral opacity eyes (88.5%) achieved ambulatory vision (P = 0.012). Of all the surgical indications, unilateral sclerocornea was associated with the worst visual outcome—only 12.5% obtained ambulatory vision. Additional intraocular surgery was also associated with a reduced ambulatory visual acuity outcome. There were no significant differences in visual acuity among the different follow-up subgroups (<12 months, 12–36 months, and >36 months after operation; P = 0.928). Patients with bilateral opacity had a higher proportion of abnormal amplitude flash visual-evoked potentials than did patients with unilateral opacity (P = 0.033). Ten of the 14 eyes that achieved 20/260 vision had corneal astigmatism ≤3 diopters.

Conclusions:

Most of the clear grafts after PK in children with congenital corneal opacities achieved ambulatory vision. The visual outcome was better in binocular opacity cases than in monocular ones.
Bronchoscopically Delivered Thermal Vapor Ablation of Human Lung Lesions
Authors: Ferguson J. Scott , Henne Erik
Published: July 2018

Background:

The discovery that early diagnosis can reduce the mortality of lung cancer provides firm evidence that early surgical intervention is effective. However, surgical resection is available only to those who are healthy enough to tolerate the procedure. Vapor ablation may provide an additional method of treating the lung cancer patient, and has been studied in humans for emphysema treatment. In swine, we previously demonstrated that bronchoscopically delivered thermal vapor ablation (BTVA) could be accurately applied, was uniform, anatomically confined, and was tolerated by the animal. To provide evidence that BTVA may be a feasible method of treatment in humans, and since human and swine lungs have differing airway and segmental anatomy, we extended our studies to deceased human lungs to determine if anatomically confined and uniform ablations could be obtained with levels of energy comparable with our swine and human emphysema studies.

Methods:

We obtained fresh, deceased human lungs and performed BTVA with increasing energy in subsegmental regions of lung containing tumors as well as non–tumor-containing areas in order to determine if uniform ablations with sharp boundaries could be obtained in human lung.

Results:

We found that all ablations were anatomically contained. The frequency of uniform ablation effect was dependent on the total energy delivered and was achieved at a greater frequency than those with sharp boundaries. If a lung tumor was contained within the anatomy of the subsegment, the ablation zone completely surrounded the tumor.

Conclusion:

We conclude that BTVA may have a future role in the treatment of lung cancer and should be investigated further in clinical trials.