bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of nabilone for acute chemotherapy‐induced vomiting prophylaxis in pediatric patients: A multicenter, retrospective review
Authors: Polito Samantha , MacDonald Tamara , Romanick Marcel , Jupp Jennifer , Wiernikowski John , Vennettilli Ashlee , Khanna Mila , Patel Priya , Ning Winnie , Sung Lillian , Dupuis L. Lee
Published: July 2018

Objectives

To describe the safety and efficacy of nabilone given to pediatric patients to prevent acute chemotherapy‐induced nausea and vomiting (CINV).

Methods

A multicenter, retrospective review of pediatric patients who received nabilone for acute CINV prophylaxis between December 1, 2010 and August 1, 2015 was undertaken. One course of nabilone was evaluated per patient. Adverse effects associated with nabilone use were noted. The proportion of patients who experienced complete acute chemotherapy‐induced vomiting (CIV) control during the acute phase was determined. The acute phase was defined as starting with the first chemotherapy dose and continuing until 24 h after administration of the last chemotherapy dose of the chemotherapy block.

Results

One hundred ten eligible patients (median age: 14.0 years, range: 1.1–18.0 years; 65 male) were identified. Most (109/110) received nabilone plus a 5‐HT3 antagonist for CINV prophylaxis. Adverse effects associated with nabilone were experienced by 34% (37/110) of children. All were of CTCAE Version 4.03 Grade 2 or less. Sedation (20.0%), dizziness (10.0%), and euphoria (3.6%) were the most commonly reported adverse events. Nabilone was discontinued in 10 patients due to an adverse event. The proportions of patients receiving highly or moderately emetogenic chemotherapy who experienced complete acute CIV control were 50.6% (42/83) and 53.8% (14/26), respectively.

Conclusion

Adverse events associated with nabilone were common but of minor clinical significance. Acute CIV control in children receiving nabilone as a part of their antiemetic regimen was poor. Future work should focus on implementation of guideline‐consistent CINV prophylaxis and treatment.
Preparation and Sensitivity Property of Nitrocellulose/Silica Composite with Silica Gel as Coating Layer
Authors: Meng Xiangjun , Xiao Zhenggang
Published: July 2018

The safety performance of propellants is one of the important issues that must be considered in their application and it is mainly determined by their sensitivity. Thus, the reduction of the sensitivity exhibited by propellants is an effective measure to improve their safety. The sensitivity of traditional propellants is partly resulted from nitrocellulose, and preparation and application of less sensitive nitrocellulose can reduce their sensitivity. However, the nitrocellulose has gained little development from the invention on the sensitivity research. The surface of nitrocellulose was grafted with the silica gel by sol‐gel method to prepare an insensitive nitrocellulose in the paper. The product was characterized by FT‐IR, SEM, XRD, XPS, TGA, DSC and sensitivity tests. Results show that the nitrocellulose surface is coated with the silica gel successfully, and its crystal form is not affected by silica gel. Furthermore, the impact sensitivities of NC/SiO2 composites are reduced significantly in comparison with pure nitrocellulose.
Entropic allostery dominates the phosphorylation‐dependent regulation of Syk tyrosine kinase release from immunoreceptor tyrosine‐based activation motifs
Authors: Feng Chao , Roy Amitava , Post Carol Beth
Published: July 2018

Spleen tyrosine kinase (Syk) is an essential player in immune signaling through its ability to couple multiple classes of membrane immunoreceptors to intracellular signaling pathways. Ligand binding leads to the recruitment of Syk to a phosphorylated cytoplasmic region of the receptors called ITAM. Syk binds to ITAM with high‐affinity (nanomolar Kd) via its tandem pair of SH2 domains. The affinity between Syk and ITAM is allosterically regulated by phosphorylation at Y130 in a linker connecting the tandem SH2 domains; when Y130 is phosphorylated, the binding affinity decreases (micromolar Kd). Previous equilibrium binding studies attribute the increase in the binding free energy to an intra‐molecular binding (isomerization) step of the tandem SH2 and ITAM, but a physical basis for the increased free energy is unknown. Here, we provide evidence that Y130 phosphorylation imposes an entropy penalty to isomerization, but surprisingly, has negligible effect on the SH2 binding interactions with ITAM and thus on the binding enthalpy. An analysis of NMR chemical shift differences characterized conformational effects of ITAM binding, and binding thermodynamics were measured from isothermal titration calorimetry. Together the data support a previously unknown mechanism for the basis of regulating protein–protein interactions through protein phosphorylation. The decreased affinity for Syk association with immune receptor ITAMs by Y130 phosphorylation is an allosteric mechanism driven by an increased entropy penalty, likely contributed by conformational disorder in the SH2–SH2 inter‐domain structure, while SH2‐ITAM binding contacts are not affected, and binding enthalpy is unchanged.
Wnt receptor Frizzled 8 is a target of ERG in prostate cancer
Authors: Chakravarthi Balabhadrapatruni V. S. K. , Chandrashekar Darshan S. , Hodigere Balasubramanya Sai Akshaya , Robinson Alyncia D. , Carskadon Shannon , Rao Uttam , Gordetsky Jennifer , Manne Upender , Netto George J. , Sudarshan Sunil , Palanisamy Nallasivam , Varambally Sooryanarayana
Published: July 2018

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overexpression of ERG in the majority of prostate cancers. Overexpression of ERG plays a critical role in prostate oncogenesis and development of metastatic disease. Among the downstream effectors of ERG, Frizzled family member FZD4 has been shown to be a target of ERG. Frizzled‐8 (FZD8) has been shown to be involved in PCa bone metastasis. In the present study, we show that the expression of FZD8 is directly correlated with ERG expression in PCa. Furthermore, we show that ERG directly targets and activates FZD8 by binding to its promoter. This activation is specific to ETS transcription factor ERG and not ETV1. We propose that ERG overexpression in PCa leads to induction of Frizzled family member FZD8, which is known to activate the Wnt pathway. Taken together, these findings uncover a novel mechanism for PCa metastasis, and indicate that FZD8 may represent a potential therapeutic target for PCa.
Effect of virgin avocado oil on diet‐induced hypercholesterolemia in rats via 1H NMR‐based metabolomics approach
Authors: Tan Chin Xuan , Chong Gun Hean , Hamzah Hazilawati , Ghazali Hasanah Mohd
Published: July 2018

Hypercholesterolemia is a major risk factor for the initiation and development of nonalcoholic fatty liver disease and atherosclerosis. The present study evaluated the hypocholesterolemic effect of virgin avocado oil (VAO) using urinary metabolomic method. Male Sprague–Dawley rats were fed high‐cholesterol diet for four weeks to induce hypercholesterolemia. After confirming the establishment of hypercholesterolemia model, the VAO (450 and 900 mg·kg−1·day−1) and simvastatin (10 mg·kg−1·day−1) were given orally while maintaining the high‐cholesterol diet for another four weeks. Assessment of urinary metabolomics using NMR revealed that VAO treatment could partially recover the metabolism dysfunction induced by hypercholesterolemia mainly via lipid, energy, amino acid, and gut microbiota metabolism.
Simulating systems with fast and slow dynamics: lessons from the electric power industry
Authors: Ford Andrew
Published: July 2018

Complex systems exhibit dynamics across multiple timescales. Strong couplings across timescales can be important, but common practice has been to ignore the couplings. This paper describes my experience modeling electric power systems when clients argued for models including both fast and slow dynamics. Their goals were realism, transparency for policymakers and fast simulations to enable policy design and sensitivity analysis in live workshop settings. I describe different methods developed to meet these needs using five modeling studies conducted over three decades. The studies focused on important policy issues, which are described for context. I summarize the strengths and weaknesses of each method, with emphasis on their applicability beyond the power industry. The paper concludes with an endorsement of a coupled system with a stand‐alone model of fast dynamics to support the design of the long‐term model. The appendices provide details to help those interested in applying the methods.

Copyright © 2018 System Dynamics Society
Lewis Acidic Ionic Liquid Immobilized on Graphene Oxide: Synthesis, Characterization, and Application in the Ultrasound‐Assisted Condensation Reactions
Authors: Zand Hamid Reza Esmaili , Ghafuri Hossein , Ghanbari Nastaran
Published: July 2018

The catalytic activity of a novel Lewis acidic Fe(III)/caffeine‐based ionic liquid immobilized on graphene oxide (Caff‐IL‐GO/Fe) was studied in three condensation reactions in water under sonication. This catalyst was characterized by Fourier‐transform infrared spectroscopy, proton nuclear magnetic resonance, thermal gravimetric analysis, energy‐dispersive X‐ray spectroscopy, field emission scanning electron microscopy, powder X‐ray diffraction, and atomic force microscopy. The performance of the synthesized Caff–IL–GO nanocatalyst was investigated in the one‐pot ultrasound‐assisted synthesis of substituted 4H‐pyrans, dihydropyrimidinones and benzimidazoles. The Caff‐IL‐GO/Fe nanocatalyst exhibited excellent activity and delivered corresponding products in high to excellent yields. Additionally, the reusability and stability of the Caff–IL–GO was also investigated. Our study indicated that the nanocatalyst could be reused up to 10 times without any significant loss of activity.
Novel Organic Compounds Containing Nitramine Groups Suitable as High‐Energy Cyclic Nitramine Compounds
Authors: Keshavarz Mohammad Hossein , Abadi Yasin Hayat
Published: July 2018

This work introduces eight novel cyclic nitramine derivatives of energetic compounds as high performance energetic compounds. Assessments of physicothermal, detonation and combustion properties as well as sensitivities with respect to external stimuli impact, friction and shock are done for these compounds. The method of density functional theory (DFT) at B3LYP/6‐31G (d,p) as well as the best available predictive methods are used for prediction of 20 different parameters including crystal density, solid phase heat formation, Gibbs free energy of formation, activation energy, heat of sublimation, melting point, enthalpy of fusion, entropy of fusion, heat of combustion, heat of detonation, temperature of detonation, specific impulse, velocity of detonation, detonation pressure, Gurney velocity, power, brisance, heat sensitivity, impact sensitivity, friction sensitivity and shock sensitivity. These properties are compared with corresponding measured or calculated data of octahydro‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocine (HMX) and 2,4,6,8‐tetranitro‐1H,5H‐2,4,6,8‐tetraazabicyclo [3.3.0] octane (BCHMX) as two high performance nitramines. Among the introduced cyclic nitramines, it shown that N,N‐bis(1,3,4,6‐tetranitrooctahydroimidazo[4, 5‐d]imidazol‐2‐yl) nitramide is a good candidate of high performance nitramine where its sensitivity with respect to impact, friction and shock is close to BCHMX.
A Dicobalt Coordination Complex with a Short Cobalt‐Cobalt Distance
Authors: Kumar Jayasree , Gorantla N. V. T. Sai Manoj , Roy Sudipta , Paesch Alexander Noel , Herbst‐Irmer Regine , Stalke Dietmar , Anusha Chakkittakandiyil , De Susmita , Parameswaran Pattiyil , Roesky Herbert W. , Mondal Kartik Chandra
Published: July 2018

The existence of a metal‐metal bond in organometallic and coordination complexes is a very important aspect. Metal‐carbonyl, carbene‐metal‐carbonyl and metal‐carbene complexes were studied for having this feature. Herein, an air stable dark green color dicobalt coordination complex [Co(III)2(hep)3(N3)3] (1) [hepH = 2‐(2‐ethylhydroxy)pyridine] with three μ‐alkoxide bridges has been synthesized and characterized by X‐ray single crystal diffraction, NMR and UV/vis spectroscopy. Complex 1 has a short Co⋅⋅⋅Co distance (2.595(6) Å) and thus it has been studied by theoretical calculations. QTAIM (quantum theory of atoms in molecules) as well as EDA‐NOCV analysis (energy decomposition analysis ‐ natural orbitals for chemical valence) do not indicate any significant metal‐metal interaction. The bonding in 1 can be best represented by the interaction of two alkokxy bridged valence electrons fragment Co(III)(hep)2N3 (3d6) with Co(III)(hep)(N3)2 (3d6) where the donation of the lone pair of electrons from three bridging Ohep‐atoms stabilizes the dinuclear Co(III) complex. Additionally, thermolysis of 1 at 550 oC led to the formation sponge like Co3O4 oxide.
Chiral to Chiral Phase Transition in a Novel Hydrogen Bond Type Molecular Ferroelectric
Authors: Yang Changshan , Tan Yuhui , Wang Changfeng , Chen Shaopeng , Wen Herui , Tang Yunzhi
Published: July 2018

Although great progress has been made for H‐bonds type molecular ferroelectrics, the systems accompanying with chiral to chiral phase transitions are still very spare. Here we display a new hydrogen bond type molecular ferroelectric, the salt of 1‐(1‐naphthyl) ethylammonium‐nopinate, 1, which undergoes a paraelectric–ferroelectric phase transition around 202 K from one chiral point group (P212121) to another chiral point group (P21). The electric hysteresis loop under 100 K directly indicates it is a potential ferroelectric material with maximum spontaneous polarization (Ps) 2.3 uC/cm2. X‐ray single crystal diffraction analysis shows that the significant hydrogen bond change along the b‐axis direction results net dipole moment and leads to the spontaneous polarization. The exceptional dielectric response in the vicinity of 202 K exhibits remarkable dielectric anomalies along the b‐axis direction than the other two directions. The strong SHG (second harmonic generation) signal (‐1.31) without obvious changes dependence on temperature further confirm the chiral to chiral structural phase transition.
Multifunctional Lanthanide Complexes: Mesomorphism, Photoluminescence and Second Order NLO Property
Authors: Chakrabarty Rupam , Dutta Abhijit , Roy Sushmita , Das Gobinda , Ledoux‐Rak Isabelle , Mondal Paritosh , Prasad Subbarao. K. , Rao Doddamane S. S. , Bhattacharjee Chira R.
Published: July 2018

A series of new mononuclear multifunctional lanthanide(III)‐Schiff base complexes have been synthesized and characterized by elemental analyses, FTIR, 1H NMR and UV/Vis spectroscopy. Potentially tridentate, the Schiff‐base ligand is based on a ‘salicyldimine’ core with a long and flexible alkoxy group which coordinates to lanthanide ions in its zwitterionic form via the phenolic‐oxygen with the proton shifted to the imine‐nitrogen. The chelate nitrato groups complete a nine‐coordinate geometry. The ligand is non‐mesomorphic, while coordination to Ln3+ ion induces a liquid crystalline behavior. The complexes exhibited a thermally stable highly viscous partially bilayer smectic Ad phase in the 45‐135°C temperature range. The molecular organization of the complexes in the mesophase is conjectured to be based on a cylindrical‐like dimeric structure with the three alkoxy group pointing up and three pointing down assembling laterally into a lamellae. The Schiff base ligand is a blue light emitter exhibiting a broad emission maximum at 435 nm while the lanthanide complexes show an intense green emission. The Tb3+ complex, interestingly, also showed mesophase luminescence. The ligand and its complexes of La3+, Dy3+ and Yb3+ exhibited a significant second order non‐linear optical (NLO) activity representing the first example of lanthanidomesogens to exhibit such behaviour.
Competing with complementors: An empirical look at Amazon.com
Authors: Zhu Feng , Liu Qihong
Published: July 2018

Research Summary: Platform owners sometimes enter complementors' product spaces and compete against them. Using data from Amazon.com to study Amazon's entry pattern into third‐party sellers' product spaces, we find that Amazon is more likely to target successful product spaces. We also find that Amazon is less likely to enter product spaces that require greater seller efforts to grow, suggesting that complementors' platform‐specific investments influence platform owners' entry decisions. While Amazon's entry discourages affected third‐party sellers from subsequently pursuing growth on the platform, it increases product demand and reduces shipping costs for consumers. We consider the implications of these findings for complementors in platform‐based markets.

Managerial Summary: Platform owners can exert considerable influence over their complementors' welfare. Many complementors with successful products are pushed out of markets because platform owners enter their product spaces and compete directly with them. To mitigate such risks, complementors could build their businesses by aggregating nonblockbuster products or focusing on products requiring significant platform‐specific investments to grow. They should also develop capabilities in new product discovery so that they could continually bring innovative products to their platforms.
Developments in Hydroxypropylation of Starch: A Review
Authors: Fu Zhen , Zhang Lu , Ren Min‐Hong , BeMiller James N.
Published: July 2018

Because hydroxypropyl starch (HPS) represents an important chemical modification of starch, extensive studies on hydroxypropylation are being carried out at various research centers worldwide. The present review summarizes development of methods for determination of the MS (molar substitution)/DS (degree of substitution) of hydroxypropyl starch, location of hydroxypropylation reaction sites in granules and on amylose and amylopectin molecules, and factors affecting reaction efficiency. Also presented is an overview of changes of physicochemical properties of starch that result from hydroxypropylation. Specifically reviewed are the effects of hydroxypropylation on granule morphology, crystallinity, thermal properties, swelling, and solubility; pasting, paste, and retrogradation properties; rheological and textural properties of HPS gels; and digestibility and uses of HPS.
Fuzzy magnetorheological device vibration control of the two Timoshenko cantilever beams interconnected under earthquake excitation
Authors: Ndemanou Buris Peggy , Nbendjo Blaise Romeo Nana
Published: July 2018

This paper deals with the nonstationary random response of the two tall buildings connected via a magnetorheological device. The Timoshenko cantilever beam approach is used to model each of the structures. An analytical procedure for obtaining the modal equations of the whole structural system is detailed. By applying numerically the peak of root‐mean‐square displacement approach, the optimal attachment point of the control device on the structures benefited to the first two vibration modes is determined. Furthermore, a fuzzy controller rule is used to model the failure data by computing the desired voltage leading to a good control at each mode.
A review of ground‐based radar as a noncontact sensor for structural health monitoring of in‐field wind turbines blades
Authors: Ochieng Francis Xavier , Hancock Craig Matthew , Roberts Gethin Wyn , Le Kernec Julien
Published: July 2018

Ground‐based radar (GBR) are increasingly being used either as a vibration‐based or as guided‐wave‐based structural health monitoring (SHM) sensors for monitoring of wind turbines blades. Despite various studies mentioning the use of radar as transducer for SHM, a singular exclusive review of GBR in blade monitoring may have been lacking.

Various studies undertaken for SHM of blades using GBR have largely been laboratory‐based or with actual wind turbines in parked positions or focussed on the extraction of only specific condition parameters like frequency or deflection with no validation with actual expected operating data. The present study provides quantitative data that relates in‐field monitoring of wind turbines by GBR with actual design operating data. As such it helps the monitoring of blades during design, testing, and operation. Further, it supports the determination of fatigue damage for in‐field wind turbine blades especially those made of composite materials by way of condition parameters residuals and deflection.

A review of the two GBR–SHM approaches is thus undertaken. Additionally, a case study demonstrating its practical use as a vibration‐based noncontact SHM sensors is also provided. The study contributes to the monitoring of blades during design, testing, and operation. Further, it supports the determination of damage detection for in‐field wind turbine blades within a 3‐tier SHM framework especially those made of composite materials by way of condition parameter residuals of extracted modal frequencies and deflection.
Inference enterprise models: An approach to organizational performance improvement
Authors: Buede Dennis M. , Axelrad Elise T. , Brown David P. , Hudson Daniel W. , Laskey Kathryn B. , Sticha Paul J. , Thomas Jordan L.
Published: July 2018

We demonstrate that our success in solving a set of increasingly complex challenge problems is associated with an inference enterprise (IE) using inference enterprise models (IEMs). As part of a sponsored research competition, we created a multimodeling inference enterprise modeling (MIEM) process to achieve winning scores on a spectrum of challenge problems related to insider threat detection. We present in general terms the motivation for and description of our MIEM solution. We then present the results of applying MIEM across a range of challenge problems, with a detailed illustration for one challenge problem. Finally, we discuss the science and promise of IEM and MIEM, including the applicability of MIEM to a spectrum of inference domains.

This article is categorized under:

Technologies > Machine Learning

Algorithmic Development > Ensemble Methods

Technologies > Prediction
Discrete gauging in six dimensions
Authors: Hanany Amihay , Zafrir Gabi
Published: July 2018

Abstract

When n M5 branes coincide on an A type singularity, ℂ2
/ℤ
k
, there is a multitude of tensionless strings which arise in the spectrum. The low energy theory when all M5 branes are separated at the singularity is given by a linear quiver with parameters n and k. The theory has a multitude of phases, as many as partitions of n, each characterized by a different Higgs branch. Each such Higgs branch can be described by a Coulomb branch of a 3d

$$ \mathcal{N}=4 $$

N
=
4

quiver. For example, at finite coupling, when all branes are separated, the quiver has a bouquet of n U(1) nodes connected to a single node. There is a natural discrete non Abelian S

n
global symmetry which acts in the theory by permuting n identical objects. It acts in particular on the Higgs branch at the above finite coupling phase. It is conjectured that at the coincident point this discrete S

n
flavor symmetry is gauged, and at partial coincidence the corresponding subgroup of S

n
is gauged. This elegant and simple effect solves several problems which are raised recently on the physics of multiple M5 branes on an A type singularity. Similar results on multitude of phases are concluded for a system of n M5 branes on an A type singularity next to an M9 plane.
Static Prognostic Factors and Appropriate Surgical Designs for Patients with Medullary Thyroid Carcinoma: The Second Report from a Single‐Institution Study in Japan
Authors: Ito Yasuhiro , Miyauchi Akira , Kihara Minoru , Higashiiyama Takuya , Fukushima Mitsuhiro , Miya Akihiro
Published: July 2018

Background

Medullary thyroid carcinoma (MTC) originates from calcitonin‐producing cells of the thyroid.
In 2009, we published our first report on the biological characteristics and prognosis of 118 MTC patients. Herein, we enrolled a larger number of patients with longer follow‐up periods to further study the biological characteristics and appropriate therapies for MTC.

Methods

In general, hemithyroidectomy and total thyroidectomy were performed for sporadic MTC confined to the thyroid lobe and for hereditary MTC with central node dissection, respectively. Moreover, prophylactic modified radical neck dissection was performed on the side of macroscopic tumors.

Results

In total, 233 patients (99 hereditary and 134 sporadic) were enrolled. The median follow‐up time was 128 months (range 7–445 months). Biochemical cure was obtained in 36 (62%) of the 58 patients who underwent prophylactic MND and were pathologically positive for lateral node metastasis. None of the patients had recurrence in the preserved thyroid. Distant recurrence was detected in 19 patients, and 12 died of MTC. Preoperative calcitonin and carcinoembryonic antigen levels, tumor size (T) > 4 cm, the male sex, clinical and pathological node metastases (N1), distant metastasis (M1), extrathyroid extension (Ex), and a lack of biochemical cure had prognostic impacts on distant recurrence and/or carcinoma‐related mortality on univariate analysis. On multivariate analysis, Ex was independently correlated with distant recurrence, and Ex, T > 4 cm, and M1 independently affected carcinoma‐related mortality.

Conclusion

MTC patients had excellent prognosis in our institutions, indicating that our surgical strategies were appropriate.
Expressive instructions: ethnographic insights into the creativity and improvisation entailed in teaching physical skills to medical students
Authors: Harris Anna , Rethans Jan-Joost
Published: July 2018

Introduction Creativity and improvisation are recognized as important aspects of training expertise in domains such as business and the arts, yet rarely discussed in medical education. This article examines how creativity and improvisation play out in the ways teachers give ‘expressive instructions’ to medical students when teaching physical skills.
Methods Ethnographic fieldwork was conducted in a medical school in Maastricht, the Netherlands, with first, second and third year students learning physical examination skills. Over 230 h of fieldwork was conducted in the Skills Lab, including 34 tutorials of 1.5 h duration, with 11 different teachers and over 500 students. Patterns found in the fieldnotes were thematically analyzed using an inductive approach, drawing on sociological theories of craftsmanship.
Results Findings showed that teachers improvise beyond the standardized lesson structure and classroom set-up, giving what we call, drawing on sociological theory, ‘expressive instructions’. This was visible in two main ways: 1) by teachers using their own bodies; 2) by teachers using materials that came to hand.
Discussion This research highlights the important yet underexplored role of creativity and improvisation in teaching physical skills. Creativity and improvisation appear to be particularly important when training expertise in skills that are difficult to articulate and thus require expressive instructions, due for example to their sensory nature. Focusing on how expressive instructions play out in medical education offers insights into the tacit components of expertise development, a process which builds upon a long period of teachers’ skilled practice.
Characteristics of X/γ-ray radiations by intense laser interactions with high-Z solids: The role of bremsstrahlung and radiation reactions
Authors: Wu D. , Yu W. , Zhao Y.T. , Fritzsche S. , He X.T.
Published: July 2018

In this work, characteristics of X/γ-ray radiations by intense laser interactions with high-Z solids are investigated by means of a newly developed particle-in-cell (PIC) simulation code. The PIC code takes advantage of the recently developed ionization and collision dynamics models, which make it possible to model different types of materials based on their intrinsic atomic properties. Within the simulations, both bremsstrahlung and nonlinear Compton scatterings have been included. Different target materials and laser intensities are considered for studying the parameter-dependent features of X/γ-ray radiations. The relative strength and angular distributions of X/γ ray productions from bremsstrahlung and nonlinear Compton scatterings are compared to each other. The threshold under which the nonlinear Compton scatterings become dominant over bremsstrahlung is also outlined.
01 Adolescent and Young Adult Central Nervous System Tumour Survivors: Documentation of late-effects risks and screening recommendations in British Columbia, Canada
Authors: Howard A. Fuchsia , Tran Jordan , Ullett Avril , McKenzie Michael , Goddard Karen
Published: July 2018

Survivors of adolescent and young adult (AYA) central nervous system (CNS) neoplasms are at risk for late effects (LE) - treatment-related health problems occurring more than 5 years after therapy). Since, in Canada, AYA survivors are usually followed in the community, information must be conveyed to primary care providers to guide risk-based follow-up care. Objective: To assess documentation of LE risks and screening recommendations (SR) in medical records of AYA CNS tumor survivors treated with radiation therapy. Methods: The medical records of all patients diagnosed with a CNS neoplasm (benign or malignant) at ages 15-39 years, treated between 1985 and 2010 in the province of British Columbia, surviving >5 years and discharged to the community were assessed. Documentation of LE and SR were extracted, and analyzed descriptively. Results: Among 132 survivors (52% female), treated with radiation therapy (95% partial brain, 10% craniospinal, 8% partial spine, and 4% whole brain) and chemotherapy (17%), 19% of charts included no documentation of LE risks, 26% included only non-specific documentation, and 55% had minimal documentation (1 or 2 LE). Documentation of at least one specific LE increased from 24% in 1980-1989, to 54% in 1990-1999, to 86% in 2000 – 2010. Based on treatment information, all survivors were at high-risk for LE, such as radiation induced neoplasm, meningioma and cerebrovascular events. Yet, SR were documented in only 25% of charts. Conclusions: The documentation of LE risks and screening recommendations has been limited, highlighting the need to improve written communication with primary care providers.
10 Toca 5: Toca 511 combined with Toca FC versus standard of care in patients undergoing planned resection for recurrent glioblastoma or anaplastic astrocytoma
Authors: Zadeh G , Walbert T , Perry J , Zhu J , Salacz M , Bota D , Kim L , Iwamoto F , Petrecca K , Sully S , Montellano T , Kheoh T , Das A , Cloughesy TF
Published: July 2018

Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.
30 Perceived versus quantified growth trajectory of serially-imaged low-grade gliomas
Authors: Gui Chloe , Lau Jonathan C. , Megyesi Joseph F.
Published: July 2018

Background. Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing primary brain tumours that remain relatively asymptomatic for long periods of time before transforming into aggressive high-grade gliomas. Surveillance of tumour stability is performed primarily by serial imaging. Methods. We retrospectively identified LGG patients that were managed by observation with numerous (≥8) serial magnetic resonance imaging (MRI) studies. Tumour volumes were measured by manual segmentation on imaging. Demographic information, tumour histopathological data, and radiological interpretations were collected from electronic medical records. MRI radiology reports of tumour volume stability were classified into "growth" and "no growth" interpretations. Results. Of 74 LGG patients, 10 (13.5%) patients were included in the study. A median of 11 MRIs (range, 8-18) over a median of 79.7 months (range, 39.8-113.8 months) were analyzed per patient. Tumour diameter linearly increased at a median rate of 2.17 mm/year. Cox regression analysis showed that initial tumour volume predicted time to clinical intervention, and Mann-Whitney U test found that tumours of patients diagnosed before age 50 grew more slowly. Radiology interpretations that reported "no growth" (n=66) corresponded to a median measured growth of 3.90 mL and 11.0% compared to the comparison scan. Reports of "growth" (n=36) corresponded to median measured volume increases of 9.36 mL and 20.5%. Conclusion. We retrospectively analyzed the natural history of LGGs in serially-imaged patients at a single institution. Comparisons to the literature suggest that this is a subset of particularly slow-growing and low-risk tumours. We also highlight the clinical value of performing accurate LGG volumetric analyses.
42 Use of Alisertib in an adult patient with recurrent atypical teratoid/thaboid tumor: A case report and literature review of AT/RT in adults
Authors: Kalidindi Navya , Mason Warren P
Published: July 2018

Atypical Teratoid Rhabdoid Tumors (AT/RTs) often affect children under the age of 3 and are the most common malignant CNS tumors in children younger than 6 months. It is very rare to see these tumors in patients older than 6 years of age. We discuss the case of a 14 year old male with AT/RT of the right insula. He had a prior diagnosis of Dysembryoplastic Neuroectodermal Tumor (DNET) at the age of 10, after two years of intermittent headaches, nausea, and seizures, which was treated with conformal radiation and chemotherapy for a year. Following the diagnosis of AT/RT, he underwent radiotherapy, multiple lines of chemotherapy, and two additional debulking surgeries of the left temporal lobe due to continuing progression. He was then treated with Alisertib (an Aurora-A kinase inhibitor) with good response on sequential MRIs after the first three cycles. He progressed after nine cycles of Alisertib and required further debulking surgery. Six years after his AT/RT diagnosis (and 10 years after his DNET diagnosis), the patient expired at the age of 20 due to ongoing progression. To our knowledge, this is only the second reported case of Alisertib use in a non-pediatric AT/RT case. We also performed a literature review of all reported cases of AT/RT in adults between the years 2000 – 2017 and discuss treatment options, patient demographics, and survival.
53 Alterations in the epigenetic profile of glioblastoma tumors within hypoxic tumor regions
Authors: Mansouri Sheila , Velasquez Carlos , Nassiri Farshad , Wilson Mark R. , Suppiah Suganth , Moraes Fabio , Metcalf Julie , Tung Takyee , Singh Olivia , Mansouri Alireza , Aldape Kenneth , Zadeh Gelareh
Published: July 2018

Glioblastomas are the most frequent and aggressive primary brain tumor in adults and despite recent therapeutic advances, they are resistant to treatment. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumor vasculature, leading to insufficient blood supply, hypoxic areas, and ultimately to the formation of necrosis. Hypoxia induces direct or indirect changes in the biology of solid tumor and their microenvironment through the activation of HIF transcription factors, leading to increased aggressiveness and tumor resistance to therapy. Not much is known about the epigenetic alterations induced by hypoxia and how they could alter tumor biology. In the present study, we have utilized PIMO as a specific marker of hypoxia in glioblastoma patients, treated with PIMO preoperatively. We have estimated PIMO positivity in each tumor (5-45%) and determined that it positively correlates with the hypoxia marker CA IX (r=0.57). In addition, 10 surgical PIMO cases were dissociated, immune labeled using PIMO antibody, followed by DNA isolation and methylation profiling. Our analysis of differentially top 4000 differentially methylated probes suggests that PIMO-positive (hypoxic) cells are differentially methylated compared to the PIMO-negative cells and these changes are associated with genes involved in hypoxic cellular response. We will validate these findings in additional glioblastoma cases and assess the mechanism of these epigenetic alterations in vitro in glioma stem cell culture conditions and upon exposure of the cells hypoxic conditions.
46 Integration of multiple platforms to discover idh-mutant glioma subtypes
Authors: Mamatjan Yasin , Nassiri Farshad , Bunda Severa , Moraes Fabio , Aldape Kenneth D. , Zadeh Gelareh
Published: July 2018

Purpose: Diffuse gliomas can be divided on the basis of presence or absence of mutation in IDH genes. IDH-mutant diffuse gliomas represent a wide range of clinical outcome, which is not accounted for by current clinical and pathologic parameters. We aim to identify clinically and biologically relevant subgroups within IDH-mutant gliomas to gain a deeper insight into finer sub-classification. Methods: We used 412 IDH-mutant glioma samples that were profiled by The Cancer Genome Atlas (TCGA) Research Network, utilising methylation/mRNA datasets to identify subtypes with unique molecular signatures. We applied a Similarity Network Fusion (SNF) on individual platforms and their integrations. Results: SNF approach split glioma into four groups. The integrated RNA/methylation subtype produced a highly prognostic groups that predict survival (p-value=0.003) compared to mRNA and methylation alone. We observed a high degree of correlation between integrative subtypes and somatic mutations. Groups 1&4 had higher TERT promoter mutations (35% and 16%, respectively) compared to groups 2&3. Groups 1&4 showed increased TERT expression (34% and 14% respectively), and high percentage of TP53 and ATRX mutations. Multivariate analysis after adjusting for confounding factors including grade and age showed prognostic factors associated with survival (HR=3.2, p-value=0.001) in group 4 versus others. Conclusions: The results indicate that clinically relevant alterations exist within IDH-mutant gliomas that could stratify patients for treatment. Interestingly, group 4 showed high expression of HOX genes (18/18) (p-value=0.01) and higher methylation of Hox genes (21) (p-value=0.01) compared to others. Higher expression of specific Hox genes were associated with worse survival.
Incidents That Require First Aid in Schools: Can Teachers Give First Aid?
Authors: Faydalı Saide , Küçük Sibel , Yeşilyurt Maide
Published: July 2018

Objective

School-aged children are a risk group in terms of accidents and injuries, and these factors may be the primary causes of death in children. Teachers have important roles in preventing accidents and injuries and giving first aid. The purpose of this research was to identify situations in which teachers most frequently encounter the need to administer first aid to children and whether the teachers performed the correct application in these events.

Methods

This descriptive study was conducted with 331 teachers in a city in the Central Anatolia Region. The study was approved by the local ethics committee and the participants.

Results

Of the 45.3% teachers educating children ages 6 to 15 years, 81.0% of the teachers were familiar with first aid, but only 23.0% claimed to have an adequate knowledge. In the previous year, situations that had required first aid included epistaxis (75.2%), abdominal pain (49.2%), and vomiting (39.2%). The study also investigated any accidents and injuries occurring, their causes, and the teachers’ interventions following the accidents and injuries. It was found that teachers had information about first aid, but they did not trust themselves enough to practice it.

Conclusion

Understanding the causes of accidents and injuries, finding preventive measures, and updating teachers’ knowledge about this subject are important to provide a safe educational environment. (Disaster Med Public Health Preparedness. 2019;13:456-462)
Self-normalized large deviation for supercritical branching processes
Authors: Chu Weijuan
Published: July 2018

We consider a supercritical branching process (Zn, n ≥ 0) with offspring distribution (pk, k ≥ 0) satisfying p0 = 0 and p1 > 0. By applying the self-normalized large deviation of Shao (1997) for independent and identically distributed random variables, we obtain the self-normalized large deviation for supercritical branching processes, which is the self-normalized version of the result obtained by Athreya (1994). The self-normalized large deviation can also be generalized to supercritical multitype branching processes.
Computable approximations for average Markov decision processes in continuous time
Authors: Anselmi Jonatha , Dufour François , Prieto-Rumeau Tomás
Published: July 2018

In this paper we study the numerical approximation of the optimal long-run average cost of a continuous-time Markov decision process, with Borel state and action spaces, and with bounded transition and reward rates. Our approach uses a suitable discretization of the state and action spaces to approximate the original control model. The approximation error for the optimal average reward is then bounded by a linear combination of coefficients related to the discretization of the state and action spaces, namely, the Wasserstein distance between an underlying probability measure μ and a measure with finite support, and the Hausdorff distance between the original and the discretized actions sets. When approximating μ with its empirical probability measure we obtain convergence in probability at an exponential rate. An application to a queueing system is presented.
‘The fiery circle of temptation: opt, opt’: why a minority of Italian Military Internees chose to cooperate with the Nazi-Fascists
Authors: Sanders Janet
Published: July 2018

Between 8 September 1943 and the end of the war, Italian Military Internees were confronted daily with a stark choice between continued resistance and opting to assist the Reich by fighting or working. Extraordinarily, over 600,000 said no, and endured internment or forced labour until they were liberated or died. Paradoxically, the minority who made the more predictable choice of opting to cooperate, the so-called optanti, constituted an anomaly. This article examines their motivation by giving an overview of the political background, the experience of deportation, the Lager environment and the phases and methods of propaganda. Primary sources indicate that hunger was a common denominator in their decision, but that the weight of other factors, which varied with individuals, broadly speaking fell into three categories: bleak honesty, specious cynicism and maverick idealism. These categories are illustrated by four case studies: the mass adhesion at Biala Podlaska and the individuals Pietro Faraci, Tranquillo Frigeni and Remo Faustini.
Exploring Roman and early-medieval habitation of the Rhine–Meuse delta: modelling large-scale demographic changes and corresponding land-use impact
Authors: van Lanen Rowin J. , de Kleijn Maurice T.M. , Gouw-Bouman Marjolein T.I.J. , Pierik Harm Jan
Published: July 2018

In this study we apply an evidence-based approach to model population-size fluctuations and their corresponding impact on land use during the Roman and early-medieval periods in the Rhine–Meuse delta in the present-day Netherlands. Past-population numbers are reconstructed based on Roman and early-medieval settlement patterns. Corresponding impacts of these demographic fluctuations on potential land use are calculated by integrating the newly developed demographic overviews with archaeological and geoscientific data using a new land-use model termed ‘Past Land-Use Scanner’ (PLUS). The primary aims are to reconstruct first-millennium palaeodemographics and to explore the potential of simulation modelling for testing the feasibility of archaeological hypotheses regarding past land use. Results show that in the study area the first millennium AD was characterised by two periods during which major population growth occurred: the middle-Roman period (AD 70–270) and early-medieval period C (AD 725–950). A major demographic decline of 78–85% occurred during the late-Roman period (AD 270–450), after which first-millennium population numbers never again reached middle-Roman period levels. The modelling outcomes demonstrate that the impact of population fluctuations (growth vs decline) on the limits of the natural landscape during the first millennium in general was low. During these thousand years, the natural landscape almost without exception (only scenario D deviates) provided sufficient options for arable farming, meadows and pastures and was not a limiting factor for population growth. These results underline the added value of simulation modelling for testing the feasibility of archaeological hypotheses and analysing human–landscape interactions in the past.
Being in “The Room Where it Happens”:Hamilton, Obama, and Nationalist Neoliberal Multicultural Inclusion
Authors: Galella Donatella
Published: July 2018

The two white male cosponsors, a Democrat and a Republican, dressed as King George and Hamilton, respectively, as they rapped the resolution in the state senate. InHamilton, chief creator Lin-Manuel Miranda stakes out space for an immigrant from the Caribbean who was in the room where the United States of America was founded. Based on Ron Chernow's biography,Hamiltonfollows the struggles and successes of Alexander Hamilton in a story largely told by his nemesis, Aaron Burr. The musical opened Off-Broadway at the Public Theater in 2015 and subsequently moved to Broadway. With its Founders Chic historical approach, hip-hop aesthetic, and multiracial cast, this Broadway blockbuster has earned substantial commercial and critical acclaim from across the political spectrum. Former President Barack Obama joked, “Hamilton, I'm pretty sure, is the only thing Dick Cheney and I agree on.”
The costs and benefits of replication studies
Authors: Coles Nicholas A. , Tiokhin Leonid , Scheel Anne M. , Isager Peder M. , Lakens Daniël
Published: July 2018

The debate about whether replication studies should become mainstream is essentially driven by disagreements about their costs and benefits and the best ways to allocate limited resources. Determining when replications are worthwhile requires quantifying their expected utility. We argue that a formalized framework for such evaluations can be useful for both individual decision-making and collective discussions about replication.