bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-loss saturable absorbers based on tapered fibers embedded in carbon nanotube/polymer composites
Authors: Martinez Amos , Al Araimi Mohammed , Dmitriev Artemiy , Lutsyk Petro , Li Shen , Mou Chengbo , Rozhin Alexey , Sumetsky Misha , Turitsyn Sergei
Published: December 2017

The emergence of low-dimensional materials has opened new opportunities in the fabrication of compact nonlinear photonic devices. Single-walled carbon nanotubes were among the first of those materials to attract the attention of the photonics community owing to their high third order susceptibility, broadband operation, and ultrafast response. Saturable absorption, in particular, has become a widespread application for nanotubes in the mode-locking of a fiber laser where they are used as nonlinear passive amplitude modulators to initiate pulsed operation. Numerous approaches have been proposed for the integration of nanotubes in fiber systems; these can be divided into those that rely on direct interaction (where the nanotubes are sandwiched between fiber connectors) and those that rely on lateral interaction with the evanescence field of the propagating wave. Tapered fibers, in particular, offer excellent flexibility to adjust the nonlinearity of nanotube-based devices but suffer from high losses (typically exceeding 50%) and poor saturable to non-saturable absorption ratios (typically above 1:5). In this paper, we propose a method to fabricate carbon nanotube saturable absorbers with controllable saturation power, low-losses (as low as 15%), and large saturable to non-saturable loss ratios approaching 1:1. This is achieved by optimizing the procedure of embedding tapered fibers in low-refractive index polymers. In addition, this study sheds light in the operation of these devices, highlighting a trade-off between losses and saturation power and providing guidelines for the design of saturable absorbers according to their application.
Prospects for magnetic field communications and location using quantum sensors
Authors: Gerginov V. , da Silva F. C. S. , Howe D.
Published: December 2017

Signal attenuation limits the operating range in wireless communications and location. To solve the reduced range problem, we can use low-frequency signals in combination with magnetic sensing. We propose the use of an optically pumped magnetometer as a sensor and realize a proof-of-principle detection of binary phase shift keying (BPSK) modulated signals. We demonstrate a ranging enhancement by exploiting both the magnetometer’s intrinsic sensitivity of below 1 pT/Hz1/2 and its 1 kHz operating bandwidth through the use of BPSK signals.
Interstitial effects of B and Li on the magnetic phase transition and magnetocaloric effects in Gd2In alloy
Authors: Yang Yang , Xie Yigao , Zhou Xiaoqian , Zhong Hui , Jiang Qingzheng , Ma Shengcan , Zhong Zhenchen , Cui Weibin , Wang Qiang
Published: December 2017

Interstitial effects of B and Li on the phase transition and magnetocaloric effect in Gd2In alloys had been studied. The antiferromagnetic (AFM) - ferromagnetic (FM) phase transition was found to be of first-order nature while ferromagnetic - paramagnetic (PM) phase transition was of second-order nature in B- or Li-doped Gd2In alloys. AFM-FM phase transition temperature was increased while FM-PM phase transition was decreased with more doping concentrations. During AFM-FM phase transition, the slope of temperature-dependent critical field (μ0Hcr) was increased by increased doping amounts. The magnetic entropy changes under small field change were enhanced by B and Li addition, which showed the beneficial effects of B and Li additions.
n-type anode layer, high-power MWIR superlattice LED
Authors: Muhowski A. J. , Ricker R. J. , Boggess T. F. , Prineas J. P.
Published: December 2017

Cascaded superlattice LEDs were designed, grown, fabricated, and tested with an n-type anode structure consisting of a variably doped n-GaSb buffer layer and a variable tunnel junction of n-GaxIn1−xAsySb1−y/p-GaSb in place of a conventional p-doped anode contact layer. The elimination of p-doped contact layers from the structure was found to reduce parasitic optical absorption and ohmic loss. After selecting the ideal design from the 4 stage test structures, a nominally identical 16 stage n-type anode structure was grown, yielding an MWIR radiance of 6.7 W/cm2/sr.
Low-loss Z-type barium hexaferrite composites from nanoscale ZnAl2O4 addition for high-frequency applications
Authors: Zheng Zongliang , Feng Quanyuan , Harris Vincent G.
Published: December 2017

In this study, nanocrystalline ZnAl2O4 (ZA) were introduced to Z-type barium hexaferrite (Co2Z) and the effects of ZA addition upon the crystal-phase composition, microstructure, permeability and permittivity as well as losses characteristics over a wide frequency range of 10 MHz–1 GHz have been systematically investigated. With increasing ZA content (x) from 0 to 15 wt%, the permeability μ′ at low frequencies decreased from 12.0 to 4.3, while the permittivity ε′ was decreased from 27.4 to 10.7. Correspondingly, the frequency stability of permeability and permittivity were improved and the losses were effectively reduced. When x is in the range of 5–10 wt%, the magnetic loss tan δμ is in the order of 10-2 and the dielectric loss tan δε is in the order of 10-3 at 300 MHz, which is lower by one order of magnitude compared with that of undoped Co2Z. The modified magnetic and dielectric properties are closely related to the changing phase composition and microstructure.
A variable-mode stator consequent pole memory machine
Authors: Yang Hui , Lyu Shukang , Lin Heyun , Zhu Z. Q.
Published: December 2017

In this paper, a variable-mode concept is proposed for the speed range extension of a stator-consequent-pole memory machine (SCPMM). An integrated permanent magnet (PM) and electrically excited control scheme is utilized to simplify the flux-weakening control instead of relatively complicated continuous PM magnetization control. Due to the nature of memory machine, the magnetization state of low coercive force (LCF) magnets can be easily changed by applying either a positive or negative current pulse. Therefore, the number of PM poles may be changed to satisfy the specific performance requirement under different speed ranges, i.e. the machine with all PM poles can offer high torque output while that with half PM poles provides wide constant power range. In addition, the SCPMM with non-magnetized PMs can be considered as a dual-three phase electrically excited reluctance machine, which can be fed by an open-winding based dual inverters that provide direct current (DC) bias excitation to further extend the speed range. The effectiveness of the proposed variable-mode operation for extending its operating region and improving the system reliability is verified by both finite element analysis (FEA) and experiments.
Multiferroicity around Verwey transition in Fe3O4 thin films
Authors: Mishra Shubhankar , Dey Koushik , Chowdhury Ujjal , Bhattacharya Dipten , Ghosh Chandan K. , Giri Saurav
Published: December 2017

We report observation of finite remanent polarization (∼10-80 nC/cm2) and reasonably strong magnetoelectric coupling in thin film of Fe3O4 within a temperature range from ∼40 K to Verwey transition temperature TCO ∼120 K. Both the intrinsic capacitance and remanent ferroelectric polarization decrease by ∼20-60% under 0-50 kOe field within this temperature range. The measurements using conventional techniques do not yield convincing results as the ferroelectric polarization is small and loss is large. However, use of more sophisticated protocol - which eliminates the contribution from loss and nonhysteretic polarization effectively - provides reliable information about remanent polarization and its change under magnetic field around the Verwey transition.
Direct precision frequency measurement and correction technology with double ADC
Authors: Bai L. N. , Liu H. D. , Wang T. T. , Ge X. X. , Zhai H. Q. , Zhou W.
Published: December 2017

A new method of direct precision frequency measurement is proposed in this paper, which uses the clock cursor effect between the sampling clock signal and input signal and ADC (analog to digital converter) quantization error suppression technique in the background of digital measurement with double ADC. On this basis, a precision frequency corrector is designed. Compared with the traditional frequency synthesizer, this device takes the non-standard frequency signal of the crystal oscillator as the reference to realize the standard frequency signal output through the frequency correction function. Meanwhile, the output signal is obviously narrower in range, from 0.0001 Hz to 0.1 Hz. The frequency corrector can also realize the second stability of less than 3 × 10−12 and a small frequency correction of 10−11 orders of magnitude.
Lexical accessing for ambiguous words among advanced Chinese L2 learners
Authors: Shen Helen H.
Published: December 2017

This study investigated factors associated with and strategies used by advanced Chinese L2 learners in accessing the meanings of commonly used polysemous words (lexically ambiguous words) in sentential reading. The participants included 26 learners of Chinese from a Midwest university in the US. The results showed that word frequency, meaning frequency of polysemous words, and learners’ knowledge of polysemous words affected successful lexical access in sentential contexts. Learners mainly used five types of strategies to solve lexical ambiguity problems, of which three were more frequently used: contextual cues, the intra-word analysis method, and the dominant meaning cue. Contextual cues were the most frequently used strategy.
美国学生因果连接标记语篇使用情况研究 (A study of L2 development stages of causal connectives in American students’ written Chinese)
Authors: Cao Fei
Published: December 2017

抽象

本文以美国学生初、中、高级阶段所使用的因果连接标记为样本，经过统计调查表明，英语母语学习者习得汉语因果连接标记过程呈非线性路径，两种语言中的共有义较早为学习者掌握；初级阶段较多受到母语语序影响，学生多使用因标后置式；中级阶段出现了多个词项，即母语和目的语标记词一对多或多对一情况增多，学习者容易将母语词的某个义位相对宽广的语义范围错误地推移到目的语的对应词上；高级阶段中介语因果连接标记模式的使用类型虽然越来越接近母语者，但化石化现象严重，高级阶段学习者除单用和搭配使用因果连接标记外，还出现了连用和套用模式。
Conceptualizations of sociopolitical culture in Hong Kong and Mainland China
Authors: Leung Ray C. H.
Published: December 2017

This study of media discourse focuses on how the sociopolitical culture in Hong Kong and Mainland China is conceptualized by the English-speaking press. To this end, the present research studies newspaper articles on the Hong Kong Occupy Central Movement published in Britain, the United States, and Australia. Cultural Linguistics, combined with corpus analytical techniques, is used to examine the construals ofhong kongandmainland china. A 303,455-word corpus which contains 402 articles was compiled for data analysis. It is found that the disagreement between the Hong Kong civilians and the Mainland Chinese government is often reported with metonymical conceptualizations (place for inhabitantsversusplace for the institution). In general, the sociopolitical culture in Hong Kong and Mainland China is imbued with negative emotions, disharmony, and power differences, as is evident from thebody,illness,disease,container, andpossessionconceptualizations. At the end of this paper, issues about researching conceptualizations in newspaper texts, such as the journalistic input, are discussed.
Brief guided group discussion and classroom lights: normative influence can be limited with a public request for commitment / Breve discusión guiada en grupo e iluminación del aula: la influencia normativa se puede limitar con una petición pública de compromiso
Authors: Werner Carol M. , Kent de Grey Robert G.
Published: December 2017

An initial survey indicated university students were reluctant to turn off classroom lights in part because of concerns they were not allowed to do so. An intervention was designed to teach students they had the right and responsibility to turn off lights. Short (3–5 min) guided discussions just prior to class periods emphasized that the university requested their help to save money and energy by turning off classroom lights. Classroom lights were observed during baseline, a two-week intervention and a seven-week follow-up period. Results replicated a previous study in that lights were turned off more often in guided-discussion than in no-discussion classrooms, p < .005. In separate analyses, asking students to nod their heads if they supported the programme was associated with significantly more lights left on, compared to the same guided discussion without the head nods request, p < .02. This suggests that rather than enhancing normative influence, asking for public head nods reduced participation, perhaps through diffusion of responsibility, psychological reactance or self-validation processes.
Danica Chen: From early learning to aging research
Authors: O’Donnell Marie Anne
Published: December 2017

Chen studies the cellular and genetic mechanisms that control organismal aging.
Newton: From Certainty to Probability?
Authors: Walsh Kirsten
Published: December 2017

Newton’s earliest publications contained scandalous epistemological claims: not only did he aim for certainty; he also claimed success. Some commentators argue that Newton ultimately gave up claims of certainty in favor of a high degree of probability. I argue that no such shift occurred. I examine the evidence of a probabilistic shift: a passage from query 23/31 of the Opticks and rule 4 of the Principia. Neither passage supports a probabilistic approach to natural philosophy. The aim of certainty, then, was an enduring feature of Newton’s methodology.
Experimentation by Industrial Selection
Authors: Holman Bennett , Bruner Justin
Published: December 2017

Industry is a major source of funding for scientific research. There is also a growing concern for how it corrupts researchers faced with conflicts of interest. As such, the debate has focused on whether researchers have maintained their integrity. In this article we draw on both the history of medicine and formal modeling to argue that given methodological diversity and a merit-based system, industry funding can bias a community without corrupting any particular individual. We close by considering a policy solution (i.e., independent funding) that may seem to promote unbiased inquiry but that actually exacerbates the problem without additional restrictions.
Invariance, Interpretation, and Motivation
Authors: Møller-Nielsen Thomas
Published: December 2017

In this article I assess the Invariance Principle, which states that only quantities that are invariant under the symmetries of our theories are physically real. I argue, contrary to current orthodoxy, that the variance of a quantity under a theory’s symmetries is not a sufficient basis for interpreting that theory as being uncommitted to the reality of that quantity. Rather, I argue, the variance of a quantity under symmetries only ever serves as a motivation to refrain from any commitment to the quantity in question.
DeepSynergy: predicting anti-cancer drug synergy with Deep Learning
Authors: Preuer Kristina , Lewis Richard P I , Hochreiter Sepp , Bender Andreas , Bulusu Krishna C , Klambauer Günter
Published: December 2017

Motivation

While drug combination therapies are a well-established concept in cancer treatment, identifying novel synergistic combinations is challenging due to the size of combinatorial space. However, computational approaches have emerged as a time- and cost-efficient way to prioritize combinations to test, based on recently available large-scale combination screening data. Recently, Deep Learning has had an impact in many research areas by achieving new state-of-the-art model performance. However, Deep Learning has not yet been applied to drug synergy prediction, which is the approach we present here, termed DeepSynergy. DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies.

Results

DeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error. DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines. At this task, the mean Pearson correlation coefficient between the measured and the predicted values of DeepSynergy was 0.73. Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90. Furthermore, we found that all compared methods exhibit low predictive performance when extrapolating to unexplored drugs or cell lines, which we suggest is due to limitations in the size and diversity of the dataset. We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations.

Availability and implementation

DeepSynergy is available via www.bioinf.jku.at/software/DeepSynergy.

Supplementary information

Supplementary data are available at Bioinformatics online.
Analyzing large scale genomic data on the cloud with Sparkhit
Authors: Huang Liren , Krüger Jan , Sczyrba Alexander
Published: December 2017

Motivation

The increasing amount of next-generation sequencing data poses a fundamental challenge on large scale genomic analytics. Existing tools use different distributed computational platforms to scale-out bioinformatics workloads. However, the scalability of these tools is not efficient. Moreover, they have heavy run time overheads when pre-processing large amounts of data. To address these limitations, we have developed Sparkhit: a distributed bioinformatics framework built on top of the Apache Spark platform.

Results

Sparkhit integrates a variety of analytical methods. It is implemented in the Spark extended MapReduce model. It runs 92–157 times faster than MetaSpark on metagenomic fragment recruitment and 18–32 times faster than Crossbow on data pre-processing. We analyzed 100 terabytes of data across four genomic projects in the cloud in 21 h, which includes the run times of cluster deployment and data downloading. Furthermore, our application on the entire Human Microbiome Project shotgun sequencing data was completed in 2 h, presenting an approach to easily associate large amounts of public datasets with reference data.

Availability and implementation

Sparkhit is freely available at: https://rhinempi.github.io/sparkhit/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Draft Whole Genome Sequence Analyses onPseudomonas syringaepv.actinidiaeHypersensitive Response Negative Strains Detected from Kiwifruit Bleeding Sap Samples
Authors: Biondi Enrico , Zamorano Alan , Vega Ernesto , Ardizzi Stefano , Sitta Davide , De Salvador Flavio Roberto , Campos-Vargas Reinaldo , Meneses Claudio , Perez Set , Bertaccini Assunta , Fiore Nicola
Published: December 2017

Kiwifruit bleeding sap samples, collected in Italian and Chilean orchards from symptomatic and asymptomatic plants, were evaluated for the presence of Pseudomonas syringae pv. actinidiae, the causal agent of bacterial canker. The saps were sampled during the spring in both hemispheres, before the bud sprouting, during the optimal time window for the collection of an adequate volume of sample for the early detection of the pathogen, preliminarily by molecular assays, and then through its direct isolation and identification. The results of molecular analyses showed more effectiveness in the P. syringae pv. actinidiae detection when compared with those of microbiological analyses through the pathogen isolation on the nutritive and semiselective media selected. The bleeding sap analyses allowed the isolation and identification of two hypersensitive response (HR) negative and hypovirulent P. syringae pv. actinidiae strains from different regions in Italy. Moreover, multilocus sequence analysis (MLSA) and whole genome sequence (WGS) were carried out on selected Italian and Chilean P. syringae pv. actinidiae virulent strains to verify the presence of genetic variability compared with the HR negative strains and to compare the variability of selected gene clusters between strains isolated in both countries. All the strains showed the lack of argK and coronatine gene clusters as reported for the biovar 3 P. syringae pv. actinidiae strains. Despite the biologic differences obtained in the tobacco bioassays and in pathogenicity assays, the MLSA and WGS analyses did not show significant differences between the WGS of the HR negative and HR positive strains; the difference, on the other hand, between PAC_ICE sequences of Italian and Chilean P. syringae pv. actinidiae strains was confirmed. The inability of the hypovirulent strains IPV-BO 8893 and IPV-BO 9286 to provoke HR in tobacco and the low virulence shown in this host could not be associated with mutations or recombinations in T3SS island.
Reclaiming Autologous Amputated Tissue for Limb Salvage of a Diabetic Foot Burn with Underlying Critical Limb Ischemia
Authors: Tchanque-Fossuo Catherine N. , Wishy Andrew M. , West Kaitlyn I. M. , Dawson David L. , Dahle Sara E. , Carson John G.
Published: December 2017

BACKGROUND:

Diabetes mellitus is a worldwide pandemic that impacts more than 387 million people, with 29 million individuals affected in the United States alone. Diabetic patients have a 25% lifetime risk of developing a diabetic foot ulcer (DFU). Having a DFU is associated with a risk of recurrence approaching 70%. In addition, 1 in 6 patients with DFU will have a lower-limb amputation, with an associated increase in mortality ranging from 47% to 70%. Therefore, limb salvage is critical in patients with DFU.

CASE STUDY:

This article describes the case of a 70-year-old man with diabetes mellitus, end-stage renal disease, and peripheral arterial occlusive disease who presented with a 1.5% total-body-surface-area, third-degree burn to the left hallux with dry gangrene extending to the midfoot. Ankle brachial indexes were 0.66 on the left and 0.64 on the right. Toe pressures on the left were absent because of extensive dry gangrene. His right foot had a prior transmetatarsal amputation. Using a retrograde pedal approach, a chronic total occlusion of the left posterior tibial artery was recanalized with balloon angioplasty. He then underwent a transmetatarsal amputation with closure, except that the plantar medial side could not be closed without tension. Therefore, an autologous full-thickness skin graft, from the amputation specimen, was used to bridge the defect.

DISCUSSION:

At 32-week follow-up, the wound was healed, the graft had fully incorporated, and the patient was ambulating well using custom orthotic footwear. The creative use of amputated tissue to assist with wound coverage has not been well described in the literature.
New urate-lowing therapies
Authors: Abhishek Abhishek
Published: December 2017

Purpose of review

To discuss recent studies of lesinurad and arhalofenate.

Recent findings

Lesinurad acts by blocking urate reabsorption channels URAT-1 and OAT-4. It has urate-lowering effect when used alone and in combination with xanthine oxidase inhibitors (XOIs). Its uricosuric activity depends on glomerular filtration, and its’ efficacy is impaired at eGFR less than 30 ml/min. Lesinurad monotherapy (400 mg/day) associates with serum creatinine elevations. However, this risk is substantially attenuated with coprescription of a XOI and when prescribed at a dose of 200 mg/day. Given its’ modest urate-lowering effect, and the risk of serum creatinine elevation when used alone, it is licenced for use in combination with XOI for people unable to achieve target serum uric acid with XOI alone. Lesinurad does not have the drug interactions associated with probenecid, however, it is metabolized by CYP2C9, and should be used with caution if CYP2C9 inhibitors are coprescribed. Arhalofenate also acts by blocking URAT-1; however, it also blocks the NALP-3 inflammasome providing gout-specific anti-inflammatory effect. Arhalofenate has a weaker urate-lowering effect than lesinurad and further phase III evaluation is planned.

Lesinurad provides an additional option for people with gout unable to achieve target serum uric acid with XOI alone.
Morcellation in gynecologic oncology
Authors: Chalas Eva
Published: December 2017

Purpose of review

Morcellation of uteri with unsuspected malignancies has been the focus of reports for decades. More intensive evaluation of clinical outcomes and evaluation of impact of changes in practice has occurred since the release of FDA statement advising against the use of power morcellators. The review summarizes some of the most relevant publications on this topic.

Recent findings

The Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists concur that symptomatic women should undergo appropriate evaluation, morcellation should not be performed whenever malignancy is suspected or diagnosed, and acknowledge the limitations of diagnostic testing currently available to detect leiomyosarcoma. Accurate incidence of occult leiomyosarcoma in women undergoing hysterectomy for symptomatic myomas is not known because of poor quality of data. Increased complication rates, including death, with abdominal procedures and increased societal costs have been reported. The FDA safety communication has resulted in decreased laparoscopic hysterectomy rates.

Clinical judgement and practice in accordance to clinical guidelines, based on best current scientific evidence, is recommended. Women should be aware of the limitation of current data regarding the incidence of occult leiomyosarcoma or other malignancies whenever consenting to any form of therapy for symptomatic myomas, including surgical, medical and expectant management. If surgical treatment is selected, morcellation should not be performed if a malignancy diagnosis is known or suspected. A minimally invasive surgical approach is associated with a decreased complication rate and an increased quality of life years. Research efforts should focus on improving diagnostic accuracy and efficacy of therapeutic interventions.
Oxytocin Use in Labor
Authors: Drummond Susan
Published: December 2017

Oxytocin is one of the most commonly used medications in obstetrics and has been associated with claims of negligence in cases of adverse outcomes. Errors involving intravenous oxytocin administration for induction or augmentation of labor are most commonly dose related and include failure to avoid or treat tachysystole or failure to asses or treat a fetal heart rate pattern indicative of disruption in oxygenation. Clinicians should be knowledgeable regarding pharmacokinetics of oxytocin and the effect of uterine contractions on fetal oxygenation as well as safe titration of oxytocin to achieve the desired effect while minimizing harm.
Circulatory Support with Extracorporeal Membrane Oxygenation and/or Impella for Cardiogenic Shock During Myocardial Infarction
Authors: Mourad Marc , Gaudard Philippe , De La Arena Pablo , Eliet Jacob , Zeroual Norddine , Rouvière Philippe , Roubille François , Albat Bernard , Colson Pascal H.
Published: December 2017

Temporary mechanical circulatory support (TCS) is recommended for patients with profound cardiogenic shock (CS). Extracorporeal membrane oxygenation (ECMO) and Impella are possible TCS devices, but the device choice and the implantation timing are not definitely established, specifically during acute myocardial infarction. We have analyzed the respective use of ECMO or Impella (2.5, CP, or 5.0) for CS following acute myocardial infarction, from a cohort of patients who underwent TCS within 72 hours after admission for emergency percutaneous coronary intervention (PCI) from January 2009 to April 2015. Among 88 TCS-treated patients, 42 had early TCS: 23 ECMO and 19 Impella. Cardiac management, including PCI, was similar between the two groups, but ECMO patients were sicker than Impella patients (higher blood lactate level at ICU admission, higher vasoactive-inotroic and ENCOURAGE scores before TCS implantation, p ≤ 0.02). Three patients (7%) have had TCS implantation before admission, but TCS was implanted mostly in cathlab (43%, 1 during PCI, 13 just after PCI) or soon after ICU admission (50%, n = 21). Modification of the initial TCS choice was required in 10 cases (24%) for assistance upgrading in case of Impella (n = 4) or for left ventricle unloading in case of ECMO (n = 6). Extracorporeal membrane oxygenation is the technique of choice in case of profound CS, whereas Impella devices seem more appropriate for less severe hemodynamic compromise. Interestingly, the combination of both techniques may help to overcome the limits inherent to each device.
First Report of Biventricular Percutaneous Impella Ventricular Assist Device Use in Pediatric Patients
Authors: Lasa Javier J. , Castellanos Daniel A. , Denfield Susan W. , Dreyer William J. , Tume Sebastian C. , Justino Henri , Qureshi Athar M.
Published: December 2017

There is a growing interest in the use of percutaneously delivered ventricular assist devices (PVAD) in the pediatric patient population. A 16 year old female and 18 year old male both status post heart transplantation presented with evidence of graft rejection and acute severe global systolic and diastolic heart failure necessitating hemodynamic catheterization and inotropic support. Both underwent percutaneous Impella CP LVAD (Abiomed, Danvers, MA) placement with close monitoring of right ventricular function. Although pulmonary artery wedge pressure (PAWP) improved, persistently elevated central venous pressures (CVP) and ongoing renal and liver injury prompted insertion of Impella RP RVAD. Explantation of bilateral devices was achieved within 4 days in the 18 year old patient. He would go on to require total artificial heart support before successful retransplantation. Despite bilateral PVAD support and antirejection medications, our 16 year old patient went on to develop multisystem organ failure and ultimately passed away after withdrawal of life-sustaining therapies. We report the first description of biventricular percutaneous Impella VAD for the treatment of acute decompensated heart failure in a pediatric institution. This innovative VAD option for older children/adolescents represents a less-invasive advancement in mechanical support technology with potential applicability across the pediatric population.
Platelets-to-lymphocyte ratio is a good predictor of liver fibrosis and insulin resistance in hepatitis C virus-related liver disease
Authors: Alsebaey Ayman , Elhelbawy Mostafa , Waked Imam
Published: December 2017

Background

Hepatitis C virus (HCV) is a global health problem that is complicated by liver fibrosis and insulin resistance (IR).

Aim

The aim of this study was to validate neutrophils-to-lymphocytes ratio (NLR) and platelets-to-lymphocytes ratio (PLR) as indirect biomarkers of liver fibrosis and IR in HCV patients.

Patients and methods

One hundred and fifty patients were enrolled. Physical examination, BMI, liver function tests, serum creatinine, complete blood count, serum HCV RNA count by PCR, and abdominal ultrasonography were performed. Transient elastography measurement using FibroScan was performed. Patients were classified into those with mild fibrosis (F1–F3) and significant fibrosis (F4). IR was defined as homeostasis model assessment of IR more than 2. NLR and PLR were calculated.

Results

The average age of the patients was 47.21±10.51 years, mainly men (n=119; 79.3%), and 87.3% (n=131) had IR and 44.7% (n=67) had significant fibrosis. PLR was lower in patients with IR (74.95±37.90 vs. 94.71±31.45; P=0.032) unlike the NLR, which was comparable (P>0.05). Patients with significant fibrosis had lower PLR (66.43±39.38 vs. 86.35±33.85; P=0.001) unlike NLR (P>0.05). PLR (cutoff≥77.47) had 78.9% sensitivity, 60.3% specificity, 22.4% positive predictive value, and 95.2% negative predictive value for non-IR (P=0.008). At a cutoff of at least 63.71, PLR had 73.5% sensitivity, 61.2% specificity, 70.1% positive predictive value, and 65.1% negative predictive value for nonsignificant fibrosis (P=0.001). Age and PLR (odds ratio=0.99; 95% confidence interval=0.976–0.999) were predictors of IR, whereas age, total bilirubin, serum albumin, liver stiffness, and PLR (odds ratio=0.98; 95% confidence interval=0.974–0.994) were predictors of significant fibrosis.

Conclusion

PLR is useful in distinguishing the patients with significant fibrosis or IR unlike NLR.
The Morphologic Spectrum of Sertoliform Cystadenoma of the Rete Testis
Authors: Paluru Swetha , Ulbright Thomas M. , Amin Mahul , Montironi Rodolfo , Epstein Jonathan I.
Published: December 2017

Sertoliform cystadenoma of the rete testis (SCRT) is rare with only 9 cases reported to date in the literature, none with follow-up. Four large genitourinary pathology consult services were searched. We identified 15 cases of SCRT. Men were 21 to 84 years old (mean, 46 y) and had testicular discomfort or mass. Other findings were seminoma (n=1), spermatocele (n=2), hydrocele (n=1), varicocele (n=1), and scrotal hematoma (n=1). Eight had preoperative serum tumor markers, which were normal. Tumors ranged from 0.3 to 4 cm (mean, 1.5 cm). All of them were well circumscribed with solid and cystic features and occupied on average, 73% of the rete (20% to 100%). The tumors were mostly confined within dilated channels of the rete testis and showed classic features consisting of: (1) tubules with well-formed lumina in 87% of cases; (2) well-formed tubules with no lumina in 87% of cases; and (3) cords/nests in hyalinized or myxoid stroma in 73% of cases. Other patterns included: (1) solid/sheet growth in 26% of cases; (2) individual cells in 13% of cases; (3) festoons in 13% of cases; (4) branching tubules in 7% of cases; and (5) papillary in 7% of cases. Cells were cuboidal with round to oval nuclei with small nucleoli, except at the periphery where projections into rete tubules had a more columnar appearance. In the festooning pattern, nuclei were pseudostratified and columnar with prominent nucleoli and nuclear grooves. In 4 cases, tumor extended into adjacent seminiferous tubules surrounded by dense peritubular fibrosis, with in some cases small cysts lined by flattened epithelium containing pale lightly granular material. All cases lacked necrosis and significant atypia. Mitoses ranged from 0 to 2 per 10 high-power field. Follow-up ranged from 4 to 170 months with mean of 97 months. For the 13 cases with information, all patients were alive, except for 3 who died of either unrelated causes (9.2 and 10 y) or of unknown cause (4.8 y at age 89 y). We performed immunohistochemistry for steroidogenic factor 1 and inhibin in 4 of our cases, where 3 (75%) were positive for both markers. We also describe 2 additional cases which morphologically resembled SCRT but had more atypical features. This study highlights that SCRT has variable morphology. We also verify the benign nature of the lesion and its lack of association with any syndromes.
Site-specific Differences in Colonic Adenocarcinoma
Authors: Landau Michael A. , Zhu Benjamin , Akwuole Frances N. , Pai Reetesh K.
Published: December 2017

Recent literature indicates that adenocarcinomas of the cecum differ with respect to molecular alterations compared with noncecal proximal colon adenocarcinomas and that cecal tumor site may be a prognostically relevant variable. We compared molecular alterations, histopathologic features, and disease-specific survival in a series of 328 colonic adenocarcinomas identified over a 2-year period and stratified by tumor location (cecum, right colon, and left colon). Overall, cecal adenocarcinomas demonstrated the highest frequency of molecular abnormalities with 74% harboring either a KRAS exon 2 or 3 mutation, a BRAF mutation, or DNA mismatch repair protein deficiency. KRAS mutations were more frequently seen in the cecum compared with all other tumor sites (P=0.03). KRAS mutations were identified in 46% of cecal adenocarcinomas compared with only 25% of adenocarcinomas of the right colon (P=0.004). Cecal adenocarcinomas more frequently displayed adverse histopathologic features, in particular high tumor budding (31%), compared with tumors of the right colon (18%; P=0.04) and tumors of the left colon (17%; P=0.02). Overall stage was the most important independent predictor of disease-specific survival in the multivariable analysis; however, cecal tumor site and high tumor budding were also predictive of poor survival, particularly in patients with stage III or IV tumors. In conclusion, cecal adenocarcinomas are characterized by a high frequency of KRAS mutations compared with noncecal right colon tumors, frequently display high tumor budding, and may be a prognostically relevant variable, particularly in patients with stage III or IV disease.
Version 3 of the Alzheimer Disease Centers’ Neuropsychological Test Battery in the Uniform Data Set (UDS)
Authors: Weintraub Sandra , Besser Lilah , Dodge Hiroko H. , Teylan Merilee , Ferris Steven , Goldstein Felicia C. , Giordani Bruno , Kramer Joel , Loewenstein David , Marson Dan , Mungas Dan , Salmon David , Welsh-Bohmer Kathleen , Zhou Xiao-Hua , Shirk Steven D. , Atri Alireza , Kukull Walter A. , Phelps Creighton , Morris John C.
Published: December 2017

Introduction:

The neuropsychological battery of the Uniform Data Set (UDSNB) was implemented in 2005 by the National Institute on Aging (NIA) Alzheimer Disease Centers program to measure cognitive performance in dementia and mild cognitive impairment due to Alzheimer Disease. This paper describes a revision, the UDSNB 3.0.

Methods:

The Neuropsychology Work Group of the NIA Clinical Task Force recommended revisions through a process of due diligence to address shortcomings of the original battery. The UDSNB 3.0 covers episodic memory, processing speed, executive function, language, and constructional ability. Data from 3602 cognitively normal participants in the National Alzheimer Coordinating Center database were analyzed.

Results:

Descriptive statistics are presented. Multivariable linear regression analyses demonstrated score differences by age, sex, and education and were also used to create a normative calculator available online.

Discussion:

The UDSNB 3.0 neuropsychological battery provides a valuable non proprietary resource for conducting research on cognitive aging and dementia.
Close encounters between infants and household members measured through wearable proximity sensors
Authors: Ozella Laura , Gesualdo Francesco , Tizzoni Michele , Rizzo Caterina , Pandolfi Elisabetta , Campagna Ilaria , Tozzi Alberto Eugenio , Cattuto Ciro
Published: December 2017

Describing and understanding close proximity interactions between infant and family members can provide key information on transmission opportunities of respiratory infections within households. Among respiratory infections, pertussis represents a public health priority. Pertussis infection can be particularly harmful to young, unvaccinated infants and for these patients, family members represent the main sources of transmission. Here, we report on the use of wearable proximity sensors based on RFID technology to measure face-to-face proximity between family members within 16 households with infants younger than 6 months for 2-5 consecutive days of data collection. The sensors were deployed over the course of approximately 1 year, in the context of a national research project aimed at the improvement of infant pertussis prevention strategies. We recorded 5,958 contact events between 55 individuals: 16 infants, 4 siblings, 31 parents and 4 grandparents. The contact networks showed a heterogeneous distribution of the cumulative time spent in proximity with the infant by family members. Most of the contacts occurred between the infant and other family members (70%), and many contacts were observed between infants and adults, in particular between infant and mother, followed by father, siblings and grandparents. A larger number of contacts and longer contact durations between infant and other family members were observed in families adopting exclusive breastfeeding, compared to families in which the infant receives artificial or mixed feeding.

Our results demonstrate how a high-resolution measurement of contact matrices within infants’ households is feasible using wearable proximity sensing devices. Moreover, our findings suggest the mother is responsible for the large majority of the infant’s contact pattern, thus being the main potential source of infection for a transmissible disease. As the contribution to the infants’ contact pattern by other family members is very variable, vaccination against pertussis during pregnancy is probably the best strategy to protect young, unvaccinated infants.
Three-Dimensional Binocular Eye-Hand Coordination in Normal Vision and with Simulated Visual Impairment
Authors: Maiello Guido , Kwon MiYoung , Bex Peter J.
Published: December 2017

Sensorimotor coupling in healthy humans is demonstrated by the higher accuracy of visually tracking intrinsically-rather than extrinsically-generated hand movements in the fronto-parallel plane. It is unknown whether this coupling also facilitates vergence eye movements for tracking objects in depth, or can overcome symmetric or asymmetric binocular visual impairments. Human observers were therefore asked to track with their gaze a target moving horizontally or in depth. The movement of the target was either directly controlled by the observer's hand or followed hand movements executed by the observer in a previous trial. Visual impairments were simulated by blurring stimuli independently in each eye. Accuracy was higher for self-generated movements in all conditions, demonstrating that motor signals are employed by the oculomotor system to improve the accuracy of vergence as well as horizontal eye movements. Asymmetric monocular blur affected horizontal tracking less than symmetric binocular blur, but impaired tracking in depth as much as binocular blur. There was a critical blur level up to which pursuit and vergence eye movements maintained tracking accuracy independent of blur level. Hand-eye coordination may therefore help compensate for functional deficits associated with eye disease and may be employed to augment visual impairment rehabilitation.
On Negative Heritability and Negative Estimates of Heritability
Authors: Steinsaltz David , Dahl Andy , Wachter Kenneth W.
Published: December 2017

Abstract

We consider the problem of interpreting negative maximum likelihood estimates of heritability that sometimes arise from popular statistical models of additive genetic variation. These may result from random noise acting on estimates of genuinely positive heritability, but we argue that they may also arise from misspecification of the standard additive mechanism that is supposed to justify the statistical procedure. Researchers should be open to the possibility that negative heritability estimates could reflect a real physical feature of the biological process from which the data were sampled.
Structural disruption of genomic regions containing ultraconserved elements is associated with neurodevelopmental phenotypes
Authors: McCole Ruth B. , Saylor Wren , Redin Claire , Fonseka Chamith Y. , Brand Harrison , Erceg Jelena , Talkowski Michael E. , Wu C.-ting
Published: December 2017

The development of the human brain and nervous system can be affected by genetic or environmental factors. Here we focus on characterizing the genetic perturbations that accompany and may contribute to neurodevelopmental phenotypes. Specifically, we examine two types of structural variants, namely, copy number variation and balanced chromosome rearrangements, discovered in subjects with neurodevelopmental disorders and related phenotypes. We find that a feature uniting these types of genetic aberrations is a proximity to ultraconserved elements (UCEs), which are sequences that are perfectly conserved between the reference genomes of distantly related species. In particular, while UCEs are generally depleted from copy number variant regions in healthy individuals, they are, on the whole, enriched in genomic regions disrupted by copy number variants or breakpoints of balanced rearrangements in affected individuals. Additionally, while genes associated with neurodevelopmental disorders are enriched in UCEs, this does not account for the excess of UCEs either in copy number variants or close to the breakpoints of balanced rearrangements in affected individuals. Indeed, our data are consistent with some manifestations of neurodevelopmental disorders resulting from a disruption of genome integrity in the vicinity of UCEs.
A Quantitative Assessment of Prefrontal Cortex in Humans Relative to Nonhuman Primates
Authors: Donahue Chad J , Glasser Matthew F , Preuss Todd M , Rilling James K , Van Essen David C
Published: December 2017

Humans have the largest cerebral cortex among primates. A long-standing controversy is whether association cortex, particularly prefrontal cortex (PFC), is disproportionately larger in humans compared to nonhuman primates, as some studies report that human PFC is relatively expanded whereas others report uniform PFC scaling. We address this controversy using MRI-derived cortical surfaces of many individual humans, chimpanzees, and macaques. We present two parcellation-based PFC delineations based on cytoarchitecture and function and show that a previously used morphological surrogate (cortex anterior to the genu of the corpus callosum) substantially underestimates PFC extent, especially in humans. We find that the proportion of cortical gray matter occupied by PFC in humans is up to 86% larger than in macaques and 24% larger than in chimpanzees. The disparity is even greater for PFC white matter volume, which is 140% larger in humans compared to macaques and 71% larger than in chimpanzees.
Gene editing of the multi-copy H2A.B gene family by a single pair of TALENS
Authors: Anuar Nur Diana , Field Matt , Kurscheid Sebastian , Zhang Lei , Rebar Edward , Gregory Philip , Bowles Josephine , Koopman Peter , Tremethick David J. , Soboleva Tatiana
Published: December 2017

In view of the controversy related to the generation of off-target mutations by gene editing approaches, we tested the specificity of TALENs by disrupting a multi-copy gene family using only one pair of TALENS. We show here that TALENS do display a high level of specificity by simultaneously knocking out the function of the three genes that encode for H2A.B.3. This represents the first described knockout of this histone variant.