bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurements of the weak bonding interfacial stiffness by using air-coupled ultrasound
Authors: Wu Wen-Lin , Wang Xing-Guo , Huang Zhi-Cheng , Wu Nan-Xing
Published: December 2017

An air-coupled ultrasonic method, focusing on the problem that weak bonding interface is difficult to accurately measure using conventional nondestructive testing technique, is proposed to evaluate the bond integrity. Based on the spring model and the potential function theory, a theoretical model is established to predict the through-transmission spectrum in double-layer adhesive structure. The result of a theoretical algorithm shows that all the resonant transmission peaks move towards higher frequency with the increase of the interfacial stiffness. The reason for these movements is related to either the normal stiffness (KN) or the transverse stiffness (KT). A method to optimize the measurement parameters (i.e. the incident angle and testing frequency) is put forward through analyzing the relationship between the resonant transmission peaks and the interfacial spring stiffness at the frequency below 1MHz. The air-coupled ultrasonic testing experiments at the normal and oblique incident angle respectively are carried out to verify the theoretical analysis and to accurately measure the interfacial stiffness of double-layer adhesive composite plate. The experimental results are good agreement with the results from the theoretical algorithm, and the relationship between bonding time and interfacial stiffness is presented at the end of this paper.
Development of a magnetic catheter with rotating multi-magnets to achieve unclogging motions with enhanced steering capability
Authors: Kim N. , Lee S. , Lee W. , Jang G.
Published: December 2017

We developed a novel magnetic catheter structure that can selectively generate steering and unclogging motions. The proposed magnetic catheter is composed of a flexible tube and two modules with ring magnets that can axially rotate in a way that enables the catheter to independently steer and unclog blood clots by controlling external magnetic fields. We mathematically modeled the deflection of the catheter using the large deflection Euler-Bernoulli beam model and developed a design method to determine the optimal distance between magnets in order to maximize steering performance. Finally, we prototyped the proposed magnetic catheter and conducted several experiments to verify the theoretical model and assess its steering and unclogging capabilities.
Magnetic and magnetocaloric properties of HoCr0.75Fe0.25O3 compound
Authors: Kotnana Ganesh , Babu P. D. , Jammalamadaka S. Narayana
Published: December 2017

We report on the magnetic and magnetocaloric properties of HoCr0.75Fe0.25O3 compound around the Néel temperature (TN), which is due to Cr3+ ordering. Susceptibility (χ) vs. temperature (T) graph of HoCr0.75Fe0.25O3 compound infer two transitions due to the ordering of Cr3+ moments (TN ∼ 155 K) and Ho3+ moments (TNHo ∼ 8 K). Magnetic entropy (–ΔSM) value of 1.14 J kg-1 K-1 around 157.5 K with a magnetic field (H) of 90 kOe is attributed to antiferromagnetic (AFM) ordering of Cr3+ moments. A maximum value of adiabatic temperature (ΔTad) ∼ 0.41 K around TN is obtained and is found to increases with applied magnetic field. Negative slope for H/M vs. M2 graph is evident for HoCr0.75Fe0.25O3 compound below TN, which indicates the first order phase transition. Quantified values of –ΔSM and ΔTad open the way to explore rare earth orthochromites for the MCE properties and refrigeration applications.
Investigation on high-efficiency Ga0.51In0.49P/In0.01Ga0.99As/Ge triple-junction solar cells for space applications
Authors: Zhang Lei , Niu Pingjuan , Li Yuqiang , Song Minghui , Zhang Jianxin , Ning Pingfan , Chen Peizhuan
Published: December 2017

Ga0.51In0.49P/In0.01Ga0.99As/Ge triple-junction solar cells for space applications were grown on 4 inch Ge substrates by metal organic chemical vapor deposition methods. The triple-junction solar cells were obtained by optimizing the subcell structure, showing a high open-circuit voltage of 2.77 V and a high conversion efficiency of 31% with 30.15 cm2 area under the AM0 spectrum at 25 °C. In addition, the In0.01Ga0.99As middle subcell structure was focused by optimizing in order to improve the anti radiation ability of triple-junction solar cells, and the remaining factor of conversion efficiency for middle subcell structure was enhanced from 84% to 92%. Finally, the remaining factor of external quantum efficiency for triple-junction solar cells was increased from 80% to 85.5%.
Novel mechanisms for solid-state processing and grain growth with microstructure alignment in alnico-8 based permanent magnets
Authors: Kassen Aaron G. , White Emma M. H. , Hu Liangfa , Tang Wei , Zhou Lin , Kramer Matthew J. , Anderson Iver E.
Published: December 2017

An estimated 750,000 new hybrid electric and plug-in battery vehicles, most with permanent magnet synchronous alternating current (PMAC) drive motors, took to the road in 2016 alone. Accompanied by 40% year over year growth in the EV market significant challenges exist in producing large quantities of permanent magnets (on the order of tens of millions) for reliable, low-cost traction motors [IE Agency, Energy Technology Perspectives (2017)]. Since the rare earth permanent magnet (REPM) market is essentially 100% net import reliant in the United States and has proven to have an unstable cost and supply structure in recent years, a replacement RE-free PM material must be designed or selected, fully developed, and implemented. Alnico, with its high saturation magnetization and excellent thermal stability, appears to be uniquely suited for this task. Further, while alnico typically has been considered a relatively low coercivity hard magnet, strides have been made to increase the coercivity to levels suitable for traction drive motors [W Tang, IEEE Trans. Magn., 51 (2015)]. If a simple non-cast approach for achieving near [001] easy axis grain aligned permanent magnets can be found, this would allow mass-produced final-shape anisotropic high energy product magnets suitable for usage in compact high RPM rotor designs. Therefore, a powder metallurgical approach is being explored that uses classic compression molding with “de-bind and sinter” methods, where a novel applied uniaxial loading, and an applied magnetic field may create final-shape magnets with highly textured resulting microstructures by two different mechanisms. Results indicate a positive correlation between applied uniaxial load and resulting texture (Fig. 1), along with benefits from using an applied magnetic field for improved texture, as well. The apparent mechanisms and resulting properties will be described using closed loop hysteresisgraph measurements, EBSD orientation mapping, and high-resolution SEM.
Effects of providing explicit negative evidence on students’ perception of ungrammatical sentences using –le
Authors: Li Yan , Yan Lei
Published: December 2017

This study investigates the effects of the use of explicit negative evidence in teaching on students’ perception of two types of ungrammatical Chinese sentences in which –leshould not be used. Two groups of advanced learners of Chinese were pre-tested immediately before receiving instruction that included explicit negative evidence about the use of -le, and post-tested twice: once directly after the completion of the instruction, and again four weeks later, using a grammaticality judgment test. The results of the grammaticality judgment test indicated that including explicit negative evidence in teaching helps advanced English-speaking learners of Chinese identify sentences in which –leis used incorrectly. The implication is that including negative evidence in teaching can reduce errors caused by negative transfer from a student’s native language.
Is there corporate mindfulness? An exploratory study of Buddhist-enacted spiritual leaders’ perspectives and practices
Authors: Vu Mai Chi , Gill Roger
Published: December 2017

The majority of research on mindfulness reflects a secular viewpoint to the detriment of contextualized mindfulness approaches. We contribute to the literature on organizational mindfulness by arguing that mindfulness is a wisdom-based practice that has been exploited as an instrument
for stress reduction or moment awareness techniques. We carried out in-depth interviews in Vietnam with 24 organizational leaders who are Buddhist practitioners, using thematic analysis to elucidate our argument. Our findings reveal that the practice of mindfulness is more effectively a personal
and contextual choice rather than a universal “band aid,” thus departing from secular interpretations and applications. This choice is based on understanding Buddhist teachings and principles and the combination of the Buddhist qualities of wisdom, compassion, and non-attachment.
We argue that this more effectively can enable and contribute to a wise, dynamic, and flexible approach to corporate mindfulness.
Scientific Representation and Theoretical Equivalence
Authors: Nguyen James
Published: December 2017

In this article I connect two debates in the philosophy of science: the questions of scientific representation and both model and theoretical equivalence. I argue that by paying attention to how a model is used to draw inferences about its target system, we can define a notion of theoretical equivalence that turns on whether models license the same claims about the same target systems. I briefly consider the implications of this for two questions that have recently been discussed in the context of the formal philosophy of science.
Novelty versus Replicability: Virtues and Vices in the Reward System of Science
Authors: Romero Felipe
Published: December 2017

The reward system of science is the priority rule. The first scientist making a new discovery is rewarded with prestige, while second runners get little or nothing. Michael Strevens, following Philip Kitcher, defends this reward system, arguing that it incentivizes an efficient division of cognitive labor. I argue that this assessment depends on strong implicit assumptions about the replicability of findings. I question these assumptions on the basis of metascientific evidence and argue that the priority rule systematically discourages replication. My analysis leads us to qualify Kitcher and Strevens’s contention that a priority-based reward system is normatively desirable for science.
Dissolving the Missing Heritability Problem
Authors: Bourrat Pierrick , Lu Qiaoying
Published: December 2017

Heritability estimates obtained from genome-wide association studies (GWAS) are much lower than those of traditional quantitative methods. This phenomenon has been called the “missing heritability problem.” By analyzing and comparing GWAS and traditional quantitative methods, we first show that the estimates obtained from the latter involve some terms other than additive genetic variance, while the estimates from the former do not. Second, GWAS, when used to estimate heritability, do not take into account additive epigenetic factors transmitted across generations, while traditional quantitative methods do. Given these two points we show that the missing heritability problem can largely be dissolved.
Crash Testing an Engineering Framework in Neuroscience: Does the Idea of Robustness Break Down?
Authors: Chirimuuta M.
Published: December 2017

In this article, I discuss the concept of robustness in neuroscience. Various mechanisms for making systems robust have been discussed across biology and neuroscience (e.g., redundancy and fail-safes). Many of these notions originate from engineering. I argue that concepts borrowed from engineering aid neuroscientists in (1) operationalizing robustness, (2) formulating hypotheses about mechanisms for robustness, and (3) quantifying robustness. Furthermore, I argue that the significant disanalogies between brains and engineered artifacts raise important questions about the applicability of the engineering framework. I argue that the use of such concepts should be understood as a kind of simplifying idealization.
On the Inextendibility of Space-Time
Authors: Manchak John Byron
Published: December 2017

It has been argued that space-time must be inextendible—that it must be “as large as it can be” in some sense. Here, we register some skepticism with respect to this position.
1. The enduring idea and changing ideal of the university
Authors: Palfreyman David , Temple Paul
Published: December 2017

The model for the modern university and college began its long evolution c.1,000 years ago in medieval Western Europe. The ‘12th-century renaissance’ saw the emergence of universities and colleges at Bologna, Paris, Oxford, and Cambridge drawing on earlier Hellenistic learning, sustained by ‘the Golden Age of Islam’ and added to during ‘the Dark Ages’ of Western Europe. ‘The enduring idea and changing ideal of the university’ explains how medieval universities were, essentially, businesses delivering concrete skills and competencies through education to fee-paying students. Distinctly utilitarian and vocational, they opened a door to professional life for their students. Now we talk of them crucially contributing to the ‘knowledge society’.
2. What do universities and colleges do?
Authors: Palfreyman David , Temple Paul
Published: December 2017

‘What do universities and colleges do?’ explores just what the modern university and college do—their teaching, research, consultancy, and wider civic engagement. For most universities and colleges, worldwide, their main task is teaching high-school leavers to first-degree level: usually regarded as their least prestigious academic work. The other two main functions of universities and colleges are research and postgraduate teaching: the higher status academic tasks. Despite many differences between universities and colleges worldwide, it is remarkable that the Bachelor–Master–Doctor classification of academic achievement is truly global. The emancipatory model of higher education is described, with the general structure of universities and colleges into departments, schools, and faculties.
5. Students: getting in, getting on, getting out
Authors: Palfreyman David , Temple Paul
Published: December 2017

Universities and colleges are, overwhelmingly, about students and in most countries, they are a pretty diverse group, with varying aspirations. ‘Students: getting in, getting on, getting out’ considers the student journey from the admissions process, through induction, to the main part of the student journey involving day-to-day work on the academic programme, assessment, and then moving on to further study or to a graduate job. It asks whether students are partners or customers in the university/college–student relationship and explains how the picture has changed in recent years with the expansion of higher education, moving from an elite system to a mass system, and the introduction of student tuition fees.
7. Futures for the university and college
Authors: Palfreyman David , Temple Paul
Published: December 2017

What are the mission and shape, structure and culture, purposes and ambitions of the university and college to be? What is it to be a university and college now—what are they seen ‘to be for’? What might change by 2050? Is it a matter of steady evolution, careful adaptation, gentle re-invention? Or a future of instability and disruptive innovation, radical change, absolute transformation? ‘Futures for the university and college’ considers these questions and suggests that—given the university and college’s role in human capital formation, and the sifting and signalling processes, both hard to replicate without a national higher education structure—it has a relatively assured future.
Use of green fluorescent protein to monitor fungal growth in biomass hydrolysate
Authors: Nichols Nancy N , Quarterman Joshua C , Frazer Sarah E
Published: December 2017

A reporter gene encoding green fluorescent protein (GFP) was introduced into the ascomycete Coniochaeta ligniaria NRRL30616, and fluorescence of cultures was monitored as a measure of cell growth. Fluorescence in the GFP-expressing strain was measured during growth of cells in defined and complex media as well as in the liquor derived from pretreatment of corn stover, an agricultural residue. Fluorescence mirrored growth of cultures, as measured by optical density and counts of colony forming units. Because traditional methods to monitor growth cannot be used in biomass liquors due to its fibrous, dark-colored nature, the speed and convenience of using GFP to monitor growth is advantageous. Fluorescence of cultures in biomass hydrolysate also correlated with the concentration of furfural in hydrolysate. Furfural and other compounds, present in hydrolysate due to physico-chemical pretreatment of biomass, are inhibitory to fermenting microbes. Therefore, measurement of fluorescence in GFP-expressing C. ligniaria is a proxy for measures of microbial growth and furfural consumption, and serves as a convenient indicator of metabolism of fermentation inhibitors in biomass hydrolysate.
Single-molecule sequencing and optical mapping yields an improved genome of woodland strawberry (Fragaria vesca) with chromosome-scale contiguity
Authors: Edger Patrick P , VanBuren Robert , Colle Marivi , Poorten Thomas J , Wai Ching Man , Niederhuth Chad E , Alger Elizabeth I , Ou Shujun , Acharya Charlotte B , Wang Jie , Callow Pete , McKain Michael R , Shi Jinghua , Collier Chad , Xiong Zhiyong , Mower Jeffrey P , Slovin Janet P , Hytönen Timo , Jiang Ning , Childs Kevin L , Knapp Steven J
Published: December 2017

Background

Although draft genomes are available for most agronomically important plant species, the majority are incomplete, highly fragmented, and often riddled with assembly and scaffolding errors. These assembly issues hinder advances in tool development for functional genomics and systems biology.

Findings

Here we utilized a robust, cost-effective approach to produce high-quality reference genomes. We report a near-complete genome of diploid woodland strawberry (Fragaria vesca) using single-molecule real-time sequencing from Pacific Biosciences (PacBio). This assembly has a contig N50 length of ~7.9 million base pairs (Mb), representing a ~300-fold improvement of the previous version. The vast majority (>99.8%) of the assembly was anchored to 7 pseudomolecules using 2 sets of optical maps from Bionano Genomics. We obtained ~24.96 Mb of sequence not present in the previous version of the F. vesca genome and produced an improved annotation that includes 1496 new genes. Comparative syntenic analyses uncovered numerous, large-scale scaffolding errors present in each chromosome in the previously published version of the F. vesca genome.

Conclusions

Our results highlight the need to improve existing short-read based reference genomes. Furthermore, we demonstrate how genome quality impacts commonly used analyses for addressing both fundamental and applied biological questions.
Genome assembly of the Pink Ipê (Handroanthus impetiginosus, Bignoniaceae), a highly valued, ecologically keystone Neotropical timber forest tree
Authors: Silva-Junior Orzenil Bonfim , Grattapaglia Dario , Novaes Evandro , Collevatti Rosane G
Published: December 2017

Background

Handroanthus impetiginosus (Mart. ex DC.) Mattos is a keystone Neotropical hardwood tree widely distributed in seasonally dry tropical forests of South and Mesoamerica. Regarded as the “new mahogany,” it is the second most expensive timber, the most logged species in Brazil, and currently under significant illegal trading pressure. The plant produces large amounts of quinoids, specialized metabolites with documented antitumorous and antibiotic effects. The development of genomic resources is needed to better understand and conserve the diversity of the species, to empower forensic identification of the origin of timber, and to identify genes for important metabolic compounds.

Findings

The genome assembly covers 503.7 Mb (N50 = 81 316 bp), 90.4% of the 557-Mbp genome, with 13 206 scaffolds. A repeat database with 1508 sequences was developed, allowing masking of ~31% of the assembly. Depth of coverage indicated that consensus determination adequately removed haplotypes assembled separately due to the extensive heterozygosity of the species. Automatic gene prediction provided 31 688 structures and 35 479 messenger RNA transcripts, while external evidence supported a well-curated set of 28 603 high-confidence models (90% of total). Finally, we used the genomic sequence and the comprehensive gene content annotation to identify genes related to the production of specialized metabolites.

Conclusions

This genome assembly is the first well-curated resource for a Neotropical forest tree and the first one for a member of the Bignoniaceae family, opening exceptional opportunities to empower molecular, phytochemical, and breeding studies. This work should inspire the development of similar genomic resources for the largely neglected forest trees of the mega-diverse tropical biomes.
Bioeconomic modelling of grey seal predation impacts on the West of Scotland demersal fisheries
Authors: Trijoulet Vanessa , Dobby Helen , Holmes Steven J , Cook Robin M
Published: December 2017

The role grey seals have played in the performance of fisheries is controversial and a cause of much debate between fishers and conservationists. Most studies focus on the effects of seal damage to gears or fish and on prey population abundance but little attention is given to the consequences of the latter for the fisheries. We develop a model that quantifies the economic impact of grey seal predation on the West of Scotland demersal fisheries that traditionally targeted cod, haddock and whiting. Three contrasting fishing strategy scenarios are examined to assess impacts on equilibrium fleet revenues under different levels of seal predation. These include status quo fishing mortality (SQF, steady state with constant fishing mortality), open access fishing (bioeconomic equilibrium, BE) and the maximum economic yield (MEY). In all scenarios, cod emerges as the key stock. Large whitefish trawlers are most sensitive to seal predation due to their higher cod revenues but seal impacts are minor at the aggregate fishery level. Scenarios that consider dynamic fleet behaviour also show the greatest effects of seal predation. Results are sensitive to the choice of seal foraging model where a type II functional response increases sensitivity to seal predation. The cost to the fishery for each seal is estimated.
Preventive Effect of a Microclimate-Regulating System on Pressure Ulcer Development: A Prospective, Randomized Controlled Trial in Dutch Nursing Homes
Authors: van Leen Martin , Halfens Ruud , Schols Jos
Published: December 2017

OBJECTIVE:

Prevention of pressure ulcers (PrUs) is based on relieving pressure, diminishing shear stress, and controlling the skin’s microclimate. Based on the recommendations in the most recent guideline for prevention of PrUs, a pressure-relieving, shear stress–diminishing, and microclimate-controlling skin interface multilayer support system (Bedcare; Sense Textile, ‘s-Hertogenbosch, the Netherlands) has been developed for use on top of a viscoelastic foam mattress (Formafoam, Kabelfabriek Eupen, Belgium). The aim of this study was to test the PrU preventive effect of this system compared with a viscoelastic foam mattress alone.

METHODS:

A multicenter, prospective, randomized controlled trial was executed in 21 nursing homes in the Netherlands. Residents with a Braden score less than 16, a life expectancy of more than 3 months, and no PrUs during the last 3 months were asked to participate and included after informed consent. Residents were divided into 2 groups. The control group received a new high-quality viscoelastic foam mattress covered with a cotton sheet. The intervention group received the same new mattress, in combination with the newly developed multilayer system. Research nurses followed the participating residents for 12 weeks. The outcome parameter was the development of PrUs.

RESULTS:

Two hundred six residents participated in the study. Both groups had comparable demographics (eg, age, Braden score, care dependency, incontinence). In the control group, 5% of the residents developed a category 2, 3, or 4 PrU, and 9% in the intervention group did. These results were not statistically significant.

CONCLUSIONS:

This study shows that the multilayer system (Mini Overlay System, barrier mattress cover, and Stay and Transfer Sheet), when used as an integral system and in combination with a viscoelastic foam mattress, has no added value over the viscoelastic foam mattress/cotton sheet.
Theoretical Evaluation and Experimental Validation of Localized Therapeutic Hypothermia Application to Preserve Residual Hearing After Cochlear Implantation
Authors: Tamames Ilmar , King Curtis , Huang Chin-Yuh , Telischi Fred F. , Hoffer Michael E. , Rajguru Suhrud M.
Published: December 2017

Objectives:

Cochlear implantation surgery has been shown to result in trauma to inner ear sensory structures, resulting in loss of residual hearing. Localized therapeutic hypothermia has been shown in clinical care to be a neuroprotective intervention. Previously, we have shown in an experimental model that localized hypothermia protects cochlear hair cells and residual hearing function against surgical and cochlear implantation trauma. Using experimental temperature measurements carried out in human cadaver temporal bones and a finite element model of the inner ear, the present study examined the temperature distribution of a custom-designed hypothermia delivery system in the human inner ear organs.

Design:

The efficacy of the hypothermia probe and resulting heat distribution across human cochlea and surrounding tissues were modeled in three-dimensional in COMSOL. The geometry and dimensions of inner ear and temporal bones were derived from computed tomographic and magnetic resonance imaging images. Model predictions were compared with experimental observations from five human temporal bones.

Results:

In both the modeling and experimental studies, the cochlear temperature was lowered by 4 to 6 °C on the round window from a baseline of 37 °C within 16 to 18 minutes. The model simulations showed uniformly distributed cooling across the cochlea. This study provides insight for design, operation, and protocols for efficacious delivery of mild therapeutic hypothermia to the human cochlea that may significantly benefit patients undergoing surgical cochlear implantation by preserving residual hearing.

Conclusion:

There was a close correlation between the results of the numerical simulations and experimental observations in this study. Our custom-designed system is capable of effectively providing mild therapeutic hypothermia locally to the human cochlea. When combined with results from in vivo animal experiments, the present study suggests that the application of localized therapeutic hypothermia may hold potential for patients with an aim to preserve residual hearing after cochlear implantation.
Mammary Analog Secretory Carcinoma With ETV6 Rearrangement Arising in the Conjunctiva and Eyelid
Authors: Bao Yongyang , Li Jiang , Zhu Yanbo
Published: December 2017

Mammary analog secretory carcinoma (MASC) of salivary gland is a recently described neoplasm that morphologically and immunohistochemically resembles secretory carcinoma of the breast. Genetically, both of them harbor ETV-6-NTRK-3 fusion rearrangement. One case of primary MASCs arising from the eyelid is reported. The patient was a 52-year-old man. Microscopically, the tumor exhibited nodular aggregation of solid, tubular, and microcystic/macrocystic structures. Characteristic “colloid-like” eosinophilic secretory material was present within intraluminal spaces. Immunohistochemically, the tumor cells were positive for mammaglobin, S-100, STAT5a, vimentin, GCDFP-15, AE1/AE3, EMA, and CK7 and were negative for DOG-1, CK5/6, and SMA. A dual color break-apart fluorescence in situ hybridization probe identified rearrangement of the ETV6 gene locus on chromosome 12. The patient had no history of breast or salivary gland tumor. The tumor was completely excised, and the patient has no evidence of recurrent disease or metastasis after 1-year follow-up. A diagnosis of primary MASC was rendered. MASC has never been reported occurring in ocular region. This type of secretory carcinoma probably originates from sweat glands or accessory lacrimal glands, Wolfring and Krause. This unique case expands the clinicopathologic landscape of MASCs for better characterization of this rare entity.
Correlation of Reflectance Confocal Microscopy and Dermatopathology Findings in a Case of Acrodermatitis Chronica Atrophicans
Authors: Gülseren Duygu , Cerroni Lorenzo , Hofmann-Wellenhof Rainer , Arzberger Edith
Published: December 2017

Acrodermatitis chronica atrophicans (ACA) that is characterized by thin, papery dry, translucent, and alopecic patches with visible superficial veins is a late cutaneous manifestation of Lyme borreliosis. Clinical findings, a history of exposure to tick bite, and serology are helpful for the diagnosis of ACA and sometimes a biopsy is performed to rule out other infectious or inflammatory processes. In this study, we report reflectance confocal microscopy (RCM) findings in a case of ACA. RCM examination revealed a flattened surface with broadened skin folds, a flattened dermoepidermal junction with few papillae and less bright basal cells and multiple small bright reflecting spots in the dermis. To the best of our knowledge, this is the first description of the RCM findings in this disorder.
Novel poly-ADP-ribose polymerase inhibitor combination strategies in ovarian cancer
Authors: McCann Kelly E.
Published: December 2017

Purpose of review

The recent United States Food and Drug Administration approvals of niraparib and olaparib as maintenance monotherapy for platinum-sensitive, high-grade ovarian cancers independent of BRCA status reflect a willingness to seek indications for poly-ADP-ribose polymerase (PARP) inhibitors beyond cancers with deleterious breast cancer 1 and breast cancer 2 mutations. In this review, I describe the rationale behind current PARP combination clinical trials with chemotherapies, angiogenesis inhibitors, cell cycle checkpoint inhibitors, and inhibitors of the phosphoinositide 3-kinase/AK thymoma/mechanistic target of rapamycin pathway.

Recent findings

PARP inhibitors have primarily been studied as monotherapy in cancers with homologous recombination repair defects based on an early understanding of PARP-1 as a base excision repair enzyme and the idea that abrogation of two DNA repair pathways cripples rapidly dividing cancer cells. It is now known that PARP-1 is a DNA damage sensor with much wider reaching roles in DNA repair processes and normal cellular functions, opening possibilities for PARP inhibitor use in other clinical contexts.

PARP inhibitor combination clinical trials are in the early stages, but will deepen our understanding of DNA repair mechanisms, cancer biology, and targeted therapies, thus contributing to the next iteration of therapeutic options for our patients.
Extracorporeal Membrane Oxygenation Bridges Inoperable Patients to Definitive Cardiac Operation
Authors: Dobrilovic Nikola , Lateef Omar , Michalak Lauren , Delibasic Maja , Raman Jaishankar
Published: December 2017

Extracorporeal membrane oxygenation (ECMO) offers an opportunity for patient recovery through complete cardiopulmonary support but is associated with complications that limit duration and overall utility. We examine the role of ECMO as a potential bridge to high-risk cardiac surgery in otherwise inoperable cases. This study reports a retrospective, multi-institution experience examining all patients for whom ECMO was used preoperatively as a bridge to definitive cardiac surgery without exception. A consecutive patient database (December 2011 through August 2017) was utilized. European System for Cardiac Risk Evaluation (EuroSCORE) 2 was calculated as a metric of patient acuity and risk assessment. Observed and expected mortality were compared. Twelve adult patients fit inclusion criteria and were supported with ECMO during the study period. There were five males and seven females. Average age was 56 (39–77) years. All 12 patients were supported with venoarterial ECMO for cardiogenic shock. This was done in preparation for corrective conventional cardiac surgery. Definitive cardiac surgical procedures included complex valve (n = 5), left ventricular assist device (n = 3), coronary artery bypass grafting (CABG; n = 2), CABG/ventricular septal defect repair (n = 1), and mitral valve replacement/CABG (n = 1). Average time of ECMO support was 200 (range 113–379) hours. Three patients were decannulated from ECMO at the conclusion of definitive cardiac surgery. Risk assessed by Logistic EuroSCORE 2 ranged from 64% to 89%. Average EuroSCORE 2–predicted mortality representing all 12 patients was 77%. Thirty day mortality was 25% (3/12), and hospital mortality was 33% (4/12). Seven patients are still alive today, with a mean survival of 37 (range 2–64) months. Two deaths were associated with gastrointestinal bleeding and two with evolving liver failure. Mean difference between the EuroSCORE 2 prediction model and actual observed 30 day mortality rate was 42.33 (95% CI 36.86–47.98) with a two-tailed, one-sample t test value of p < 0.001. ECMO can successfully be utilized as a bridge to conventional cardiac surgical procedures in critically ill patients, with a historically high mortality.
Paediatric procedural sedation and analgesia by emergency physicians in a country with a recent establishment of emergency medicine
Authors: Kuypers Maybritt I. , Smits Gaël J.P. , Baerends Eva P. , Oskam Erick , Reijners Eef P.J. , Mignot-Evers Lisette A.A. , Thijssen Wendy A.M.H. , Plötz Frans B. , Korsten Erik H.M.
Published: December 2017

Objectives

Paediatric patients receive less procedural sedation and analgesia (PSA) in the emergency department compared with adults, especially in countries where emergency medicine is at an early stage of development. The objectives of this study were to evaluate the adverse events and efficacy of paediatric PSA in a country with a recent establishment of emergency medicine and to describe which factors aided implementation.

Methods

This is a prospective, multicentre, observational study of paediatric patients undergoing PSA by the first trained emergency physicians (EPs) in The Netherlands. A standardized data collection form was used at all participating hospitals to collect data on adverse events, amnesia, pain scores, and procedure completion. A survey was used to interpret which factors had aided PSA implementation.

Results

We recorded 351 paediatric PSA. The mean age was 9.5 years (95% confidence interval: 9.1–10.0). Esketamine was most frequently used (42.4%), followed by propofol (34.7%). The adverse event rate was low (3.0%). Amnesia was present in 86.8%. The median pain score was 2 (out of 10) for patients without amnesia. Procedures were successfully completed in 93.9% of the cases.

Conclusion

Paediatric PSA provided by the first EPs in The Netherlands showed appropriate levels of sedation and analgesia with a high rate of procedure completion and a low rate of adverse events. Our paper suggests that EPs provided with a proper infrastructure of mentorship, training and guidelines can implement effective paediatric PSA.
Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion
Authors: Cellier Lucie , Perron Emilie , Pissaloux Daniel , Karanian Marie , Haddad Veronique , Alberti Laurent , de la Fouchardière Arnaud
Published: December 2017

We report 5 cases of primary intradermal nodular unpigmented tumors with a melanocytic immunophenotype associated with a novel CRTC1-TRIM11 fusion. Clinically, the cutaneous nodules were slowly growing in 3 women and 2 men (25 to 82 y old, median, 28 y) with no specific topography. Lesion size ranged from 4 to 12 mm (median, 5 mm). The tumors were strictly located in the dermis with a nodular pattern. The cells were arranged in confluent nests and fascicules. Central fibronecrotic areas were present in 2 cases. Cells were medium to large, sometimes multinucleated, and presented a spindled and epithelioid cytology with prominent nucleoli. Cytonuclear atypia was constant, and mitotic activity in hotspot areas ranged from 1 to 5/mm². Immunohistochemistry found a constant positivity with S100, MiTF, and Sox10, and a heterogenous staining by MelanA or HMB45. NTRK1 was strongly positive in 3 cases. In all cases, RNA sequencing found an invariable CRTC1(e1)-TRIM11(e2) fusion, confirmed by fluorescent in situ hybridization techniques with a TRIM11 break-apart probe. In 4/4 cases, nuclear TRIM11 expression was positive by immunohistochemistry. Fluorescent in situ hybridization techniques showed no rearrangement of NTRK1 or EWSR1, and array-comparative genomic hybridization displayed no alteration (1 case) or only a whole chromosome 7 gain (2 cases) when performed. No relapse or metastatic event was observed during follow-up [3 to 72 months (median, 14 mo)]. Cutaneous clear cell sarcoma was the main differential diagnosis. Overlapping morphologic features previously described in primary dermal melanomas and paraganglioma-like melanocytic tumors were present. The CRTC1-TRIM11 fusion appears to be specific of an unpigmented nodular tumor combining a melanocytic phenotype and low-grade tumor behavior.
Antibiotic Prophylaxis after Immediate Breast Reconstruction: The Reality of Its Efficacy
Authors: Ranganathan Kavitha , Sears Erika D. , Zhong Lin , Chung Ting-Ting , Chung Kevin C. , Kozlow Jeffrey H. , Momoh Adeyiza O. , Waljee Jennifer F.
Published: December 2017

Background:

Numerous techniques are used to prevent infection after immediate implant-based breast reconstruction. Postoperative antibiotic prophylaxis is commonly prescribed to decrease the risk of reconstructive failure, despite conflicting evidence regarding its effectiveness. The authors studied whether postoperative antibiotic prophylaxis decreases the risk of infection-related explantation in the setting of immediate prosthesis-based breast reconstruction.

Methods:

Using Truven MarketScan databases, the authors identified all patients who underwent immediate implant reconstruction between January of 2010 and June of 2014 with at least 6 months of follow-up. Postoperative antibiotic prophylaxis was defined as any oral antibiotic course to be taken postoperatively based on prescriptions filled within 14 days preoperatively through 24 hours after discharge. Reconstructive failure, defined as explantation because of infection, was the primary outcome. Secondary outcomes of interest included wound complications, infection, and readmission for infection. Multivariable regression analyses controlled for demographic variables/comorbidities.

Results:

Of the 7443 patients, 6049 (81 percent) filled prescriptions for postoperative antibiotic prophylaxis. These patients were equally likely to develop a wound complication (OR, 0.93; 95 percent CI, 0.71 to 1.23) or infection (OR, 0.89; 95 percent CI, 0.70 to 1.14), undergo explantation because of infection (OR, 0.82; 95 percent CI, 0.57 to 1.18), or require readmission for infection (OR, 1.21; 95 percent CI, 0.82 to 1.78) compared with those who did not receive antibiotics. There was no significant difference in the risk of infection-related outcomes based on postoperative antibiotic prophylaxis duration.

Conclusions:

Postoperative antibiotic prophylaxis was not associated with a reduced risk of infection or explantation following prosthesis-based breast reconstruction. Given rising rates of antibiotic resistance, focusing instead on technical considerations and the management of comorbid conditions may more effectively enhance the safety of breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Implicit reward associations impact face processing: Time-resolved evidence from event-related brain potentials and pupil dilations
Authors: Hammerschmidt Wiebke , Kagan Igor , Kulke Louisa , Schacht Annekathrin
Published: December 2017

The present study aimed at investigating whether associated motivational salience causes preferential processing of inherently neutral faces similar to emotional expressions by means of event-related brain potentials (ERPs) and changes of the pupil size. To this aim, neutral faces were implicitly associated with monetary outcome, while participants (N = 44) performed a subliminal face-matching task that ensured performance around chance level and thus an equal proportion of gain, loss, and zero outcomes. Motivational context strongly impacted processing of all – even task-irrelevant – stimuli prior to the target face, indicated by enhanced amplitudes of subsequent ERP components and increased pupil size. In a separate test session, previously associated faces as well as novel faces with emotional expressions were presented within the same task but without motivational context and performance feedback. Most importantly, previously gain-associated faces amplified the LPC, although the individually contingent face-outcome assignments were not made explicit during the learning session. Emotional expressions impacted the N170 and EPN components. Modulations of the pupil size were absent in both motivationally-associated and emotional conditions. Our findings demonstrate that neural representations of neutral stimuli can acquire increased salience via implicit learning, with an advantage for gain over loss associations.
Identification of a novel caspase cleavage site in huntingtin that regulates mutant huntingtin clearance
Authors: Martin D.D.O. , Schmidt M. E. , Nguyen Y. T. , Lazic N. , Hayden M. R.
Published: December 2017

Huntington disease (HD) is a progressive neurodegenerative disease that initially affects the striatum leading to changes in behavior and loss of motor coordination. It is caused by an expansion in the polyglutamine repeat at the N-terminus of huntingtin (HTT) that leads to aggregation of mutant HTT. The loss of wildtype function, in combination with the toxic gain of function mutation, initiates various cell death pathways. Wildtype and mutant HTT are regulated by different post-translational modifications that can positively or negatively regulate their function or toxicity. In particular, we have previously shown that caspase cleavage of mutant HTT at amino acid position aspartate 586 (D586) by caspase-6 is critical for the pathogenesis of the disease in an HD mouse model. Herein, we describe the identification of a new caspase cleavage site at position D572 that is mediated by caspase-1. Inhibition of caspase-1 also inhibits cleavage at D586 through inhibition of caspase-6. Inhibition of caspase cleavage at D572 significantly decreases mutant HTT aggregation and significantly increased the turnover of soluble mutant HTT. This suggests that caspase-1 may be a viable target to inhibit caspase cleavage of mutant HTT at both D572 and D586 to promote mutant HTT clearance.
Control of mechanical pain hypersensitivity through ligand-targeted photoablation of TrkB positive sensory neurons
Authors: Dhandapani Rahul , Arokiaraj Cynthia Mary , Taberner Francisco J. , Pacifico Paola , Raja Sruthi , Nocchi Linda , Portulano Carla , Franciosa Federica , Maffei Mariano , Hussain Ahmad Fawzi , Reis Fernanda de Castro , Reymond Luc , Perlas Emerald , Garcovich Simone , Barth Stefan , Johnsson Kai , Lechner Stefan G. , Heppenstall Paul A.
Published: December 2017

Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury. Mice in which TrkB-Cre expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment.

Highlights

TrkB+ neurons detect light touch under basal conditions

TrkB+ neurons convey mechanical allodynia in neuropathic pain states

A photosensitizing derivative of BDNF allows for photoablation of TrkB+ neurons

BDNF-guided photoablation reverses allodynia in multiple types of neuropathic pain
Inverse transformation: unleashing spatially heterogeneous dynamics with an alternative approach to XPCS data analysis
Authors: Andrews Ross N. , Narayanan Suresh , Zhang Fan , Kuzmenko Ivan , Ilavsky Jan
Published: December 2017

X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering-vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables XPCS to probe the dynamics in a broad array of materials, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fail. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. This paper proposes an alternative analysis scheme based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. Using XPCS data measured from colloidal gels, it is demonstrated that the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS.
Aluminium diboride-type structure in Ethiopian opal-CT revealed by fast Fourier transform
Authors: Gauthier J.-P. , Stephant N. , Rondeau B. , Cody J. A. , Fritsch E.
Published: December 2017

Invisible on a scanning electron microscope image of the surface of an Ethiopian opal rough fracture, a periodic arrangement was detected by fast Fourier transform. Using a mask to eliminate the continuous background and keeping only the bright spots in the reciprocal space (fast Fourier transform pattern), an image reconstructed by inverse fast Fourier transform (IFFT) emphasizes a very regular bidisperse array. Taken on a vicinal plane, the image of the successive steps of the stacking allows identification of the crystallographic structure and estimation of the parameters of this aluminium diboride-type photonic crystal. In addition, another more complex IFFT image allowed confirmation of the structure and determination of the crystallographic indexing of the steps, despite image deformation due to the tilt of the vicinal plane under the electron beam.
Grating configurations to compress free-electron laser pulses
Authors: Poletto Luca , Frassetto Fabio
Published: December 2017

The optical layout of soft X-ray grating compressors designed to provide both positive and negative group-delay dispersion (GDD) is discussed. They are tailored for chirped-pulse-amplification experiments with seeded free-electron laser sources. Designs with plane or concave gratings are discussed, depending on the sign of the GDD to be introduced.