bluuebunny/crossref_metadata_2025 huggingface dataset:
O tormento da humanidade: requerentes de asilo LGBT na Europa enfrentando os limites dos direitos humanos
Authors: Bernini Lorenzo
Published: September 2018

O que é o “humano” no humano? O que faz um ser vivente ser humano? Em caso de dúvida, quem decide se um ser vivente é um ser humano? Uma cultura política liberal baseada no valor dos direitos humanos não pode evitar essas questões. Assim, este artigo usará diferentes quadros interpretativos (Thomas Hobbes, Michel Foucault, Leo Bersani, Giorgio Agamben, Judith Butler, Lee Edelman, Jasbir Puar) para dar conta da permanência de uma decisão soberana sobre o humano no governo biopolítico do presente. Exemplo disso é condição de lésbicas, gays, bissexuais, transgêneros e intersexuais vindos do continente africano para requerer asilo na Europa. Perseguidos em seus países por sua orientação sexual ou identidade de gênero, em muitos casos atravessam o Mediterrâneo em barcos precários até a terra firme – reviravolta do destino – nas mesmas ilhas em que o fascismo italiano costumava confinar homens homossexuais. Lá, são “recebidos” em campos para imigrantes ilegais onde sua completa humanidade, negada por seus países de origem, será examinada por uma comissão. Apenas se reconhecidos como membros autênticos de uma minoria sexual eles se beneficiarão da totalidade dos direitos humanos no continente europeu. Caso contrário, correm o risco de serem forçados a sair da Europa – e da humanidade. Longe de ser uma viagem de esperança, com origem na barbaridade para chegar-se à modernidade, a jornada, iniciada na África e para a Europa, torna-se um arcaico tormento.
Residual cholesteatoma of the mastoid cavity presenting with radiologic signal of a cholesterol granuloma: A case report
Authors: Isabel Marilyn , Chénard Jean , Aron Margaret
Published: September 2018

Introduction: Cholesteatoma and cholesterol granuloma can both occur in the temporal bone. Their distinct magnetic resonance imaging (MRI) signals are generally used to help differentiate one from the other to plan appropriate treatment, which differs based on the pathology.Case presentation: We present a patient with recent-onset facial paralysis whose mastoid cavity was filled with tissue radiologically resembling cholesterol granuloma but that turned out to be cholesteatoma upon surgical exploration. Complete disease extirpation was thus completed rather than simple marsupialization, the latter of which would have been sufficient in the case of cholesterol granuloma.Discussion: Cholesteatoma, although usually hypointense on T1-weighted imaging (T1WI) MRI, hyperintense on T2-weighted imaging (T2WI) MRI and showing diffusion restriction on diffusion-weighted imaging can occasionally present with an atypical MRI signal, for example, one suggestive of cholesterol granuloma.Conclusions: The clinician should keep in mind the possible diagnosis of cholesteatoma despite an atypical MRI signal in the temporal bone.
Understanding Sense of community in Subiaco, Western Australia A Study of Human Behaviour and Movement Patterns
Authors: Swapan Abu Yousuf , Marinova Dora
Published: September 2018

Despite being an important physical environment capable of promoting social sustainability, sense of community and contributing to a better quality of life, residential streets and neighbourhoods have not attracted significant research interest until now. The integrated physical interconnected network of houses, front yards, walkways, alleyways and streets offers a high potential for community building through social interactions at a neighbourhood level. Understanding people’s movements, activities and perceptions about their streets can inform design practices and local planning policy in creating better communities. This study presents an investigation of a residential neighbourhood in Subiaco, Western Australia through the use of a mixed-method methodology based on observation and a perception survey. A total of 61 households were observed and interviewed during the spring and summer of 2016–2017 to develop useful typological models centred on activities, movements and resident perceptions. The findings endorse the importance of the residential street as a focus place for behaviour setting but argues that in the case of the Subiaco neighbourhood, which is part of a larger car-dependent metropolitain area, movement patterns– including vehicular, cycling, pedestrian modes and jaywalking, have no significant impact on social interactions. According to the perception survey, 82% of the Subiaco neighbourhood residents see activities across the street as generating the highest level of sense of community. The study expands both, the existing theory and approaches to urban planning, by emphasising the need for making neighbourhood streets the centre of liveability through better physical design which encourages and facilitates pedestrian movement.
Technology Adoption in Emission Trading Programs with Market Power
Authors: André Francisco J. , Arguedas Carmen
Published: September 2018

In this paper we study the relationship between market power in emission permit markets and endogenous technology adoption. We find that the initial distribution of permits, in particular, the amount of permits initially given to the dominant firm, is crucial in determining over- or under-investment in relation to the benchmark model without market power. Specifically, if the dominant firm is initially endowed with more permits than the corresponding cost effective allocation, this results in under-investment by the dominant firm and over-investment by the competitive fringe, regardless of the specific amount of permits given to the latter firms. The results are reversed if the dominant firm is initially endowed with relatively few permits. Also, the presence of market power results in a divergence of both abatement and technology adoption levels with respect to the benchmark scenario of perfect competition, as long as technology adoption becomes more effective in reducing abatement costs.
Is energy market integration a green light for FDI?
Authors: Costa-Campi Maria T. , Paniagua Jordi , Trujillo-Baute Elisa
Published: September 2018

This paper contributes to a better understanding of the effects of the European single market strategy by studying the effect of energy market integration (EMI) on foreign direct investment (FDI). Enforcing an EMI diminishes energy uncertainty and price volatility and signals stronger and credible institutions. FDI may, as a result, increase both within and outside the EMI area through two channels: first, via energy price converge and, second, via price dispersion reduction. We develop a formal model to explain how these mechanisms affect the capital invested abroad by heterogeneous firms. The Iberian Electricity Market (MIBEL) integration of 2007 is used to quantify the effect of EMI on FDI empirically. Gravity estimates on a global dataset including bilateral FDI data show that the integration of Portugal and Spain’s electricity market increased both the amount of FDI’s participants and the number of foreign projects. In line with our theoretical expectations, our estimates show that the increase of FDI is mainly due to the reduction in price dispersion. However, the institutional credibility signal sent by MIBEL had a greater influence than expected by the actual price reduction. Furthermore, we also observe a positive increase in FDI from neighboring countries (in this instance, France), albeit lower in magnitude
Climate Anomalies and Migration between Chinese Provinces:1987-2015
Authors: Barassi M. R. , Ercolani M. G. , Herrerias M. J. , Jin Z.
Published: September 2018

Internal migration between Chinese provinces has increased substantially since the mid-1980s. Though it is generally agreed that this has been driven by economic factors, climatic factors might also have had a part to play. The challenge is to evaluate the impact of climatic factors on migration in the simultaneous presence of changing socio-economic influences. We resolve this challenge by carrying out a statistical multivariate regression analysis on bilateral migration rates between Chinese provinces. The analysis simultaneously includes climate change in the form of climate anomalies (temperature, precipitation, sunshine) and various socio-economic factors including energy consumption. To this end we have constructed a unique three-dimensional panel dataset (time, sending province, receiving province) with bilateral migration rates between 30 provinces for the period 1987-2015. Due to the distributional properties of the data and underlying theory we use a Poisson Pseudo Maximum Likelihood (PPML) estimator but include OLS estimates for comparison. The results suggest that increases in temperature and precipitation are significant migration push factors while increased sunshine discourages push migration. Provincial differentials in per capita energy consumption and Gross Regional Product (GRP) are also significant drivers of migration.
Immediation
Authors: Kacunko Slavko
Published: September 2018

21st-century media praxis is increasingly characterised by the emerging “cultural principle”, “condition” or “culture of immediacy”. The processes summarised under the term “immediation” suggest the closure of the spatio-temporal “gap” between the agencies and the media involved, resulting in a complex interplay of social, security, scientific and economic issues. The growing interest in immediation confirms its status as a new but as – yet – underestimated paradigm for the arts, sciences and humanities which calls for a future-focused inquiry into the cultures of immediacy.

However, in academic and popular discourse, the focus is on documenting either (societal) challenges or (technical) solutions. This paper seeks to address this imbalance by responding to the urgent need for a systematic understanding of the main ways in which immediation appears: firstly, today’s worldwide closed-circuit arrangements; and secondly, live-streaming practices. It proposes an innovative combination of interdisciplinary perspectives and methods to discuss the options available to increase and enrich our understanding of immediation’s potential for boosting an immense variety of societal applications. Such future-focused research into liveness and immediacy promises, in particular, to shed light onto, firstly, the concrete impacts of creative closed-circuit arrangements on the emerging “domestication” of live streaming and, secondly, the actual measures that must be taken within emerging live streaming research to assess state-of-the-art R&D in the near future.

These issues are discussed for the purpose of opening up new routes towards future solutions for a sovereign and innovative usage of cultural techniques of immediation in creative and everyday media praxis.
Polysemous light: light as a contradictory material in Rafael Lozano-Hemmer’s work
Authors: Arozqueta Claudia
Published: September 2018

This paper is a media archaeological study focused on one of the materials that has been recurrent in Rafael Lozano-Hemmer’s installations and that has a contradictory character: light. The first part of this essay traces the historical theories about light that have fascinated the artist and shows how these theories are present in some of his works. The second part analyses the use of light as a material that helps to increase visibility and serves for care but also for control purposes. Light in Lozano-Hemmer’s work has an oxymoronic character that this paper unfolds, demonstrating its multiple contradictions and the fascination of this artist with its polysemous nature.
Mirando dentro de la caja. "El Visor de dioramas con enfoque selectivo" como caso práctico de arqueología de los medios
Authors: Martín Martínez José Vicente , Albalate Gauchía Iván
Published: September 2018

La caja óptica, como parte de la cultura del entretenimiento durante los siglos xviii y xix, fue concebida en sus distintas versiones como medio para la visualización de vistas bidimensionales. El presente artículo explica el proceso de concepción y elaboración de un dispositivo que pretende continuar con la evolución de este aparato materializando una de sus variantes técnico-conceptual de la cual no hay constancia documental de su desarrollo en su época; así, es ahora rediseñada como visor de objetos tridimensionales utilizando, en ese proceso, los principios de la arqueología de los medios como disciplina o metodología de análisis teórico-práctico.

Por una parte, desde la puesta en valor de la experiencia del espectador, en tanto que tecnológica y culturalmente estructurada por los medios; por otra, desde la consideración del diseño y la materialización de dispositivos, de la práctica, como metodología de investigación. Por último, desde la utilización de técnicas obsoletas como medio de enfatizar sus valores estéticos, utilizarlos con nuevos usos o materializar posibles vías de evolución no desarrolladas. Desde esta voluntad de rescatar y valorar las cualidades genuinas de un dispositivo obsoleto, pero innovador de un modo anacrónico, surge el Visor de dioramas con enfoque selectivo.

El Visor de dioramas con enfoque selectivo es un dispositivo óptico, dotado de lente, para la presentación y visualización de dioramas, maquetas a escala u otros objetos. Mediante dicho dispositivo el espectador puede modular la profundidad de campo, regulando la distancia entre la lente y el diorama, enfocando y desenfocando los distintos planos en los que están dispuestos los elementos ubicados en su interior.
A democracia inconclusa: um estudo da reforma sanitária brasileira
Authors: Gerschman Silvia
Published: September 2018

Trata do papel dos movimentos sociais em saúde no processo de reformulação da política de saúde, plasmado na Constituição de 1988 e denominado de Reforma Sanitária brasileira. Os percalços da sua implementação são analisados no contexto do processo de democratização do País ocorrido nos últimos 10 anos. A autora contribui para a interpretação da problemática da saúde no Brasil contemporâneo, sem a qual não se pode falar em democracia e cidadania. Através da leitura deste trabalho, os cientistas políticos e os profissionais de saúde poderão refletir acerca do lugar que ocupam no sistema e nos serviços de saúde, bem como das articulações de suas representações com a política de saúde.
A Development of Foreign Language Training Course for Local Youth Guides of Dankwian Community in Thailand
Authors: Chavangklang Pitchayapa , Chavangklang Thanaset
Published: September 2018

English language has become increasingly more important as it is used as an international language to communicate with people from other countries, especially in the tourism, which is one of Thailand’s most growing industrial sectors today. Although English is taught at all educational levels in Thailand for general purposes, there is still need for specific use of English in some areas such as local tourism places. This leads to the need for improving the English language ability of people in such areas, particularly young people, who are most likely to have influential effects not only on themselves but also their families and community as a whole. The objective of this study was to develop and evaluate a foreign language training course for Local Youth Guide at Dankwian Community - a famous pottery-making village in Thailand. The course was developed in four stages: 1) Studying background information; 2) Developing the training course of Foreign Language for Local Youth Guide; 3) Trying-out the course; and 4) Evaluating the course. The training course was implemented with a group of 60 junior high school students. The study was designed for one group pretest-posttest, using pre-post tests and a satisfaction questionnaire as study tools. The study revealed the following results. 1) The community members needed a foreign language training course which has both lecturing and workshops. 2) The course consisted of one ice-breaking module and five language modules. 3) While attending the course, participants were enthusiastic, asking questions, and actively contributing to the discussions. 4) After the course, participants significantly improved their language ability at the.05 level. The participants’ satisfaction on the training course was at the ‘very high’ level. They indicated that the course emphasized on the real life applications. These results revealed the usefulness of a short training course for local youth guides in Thailand. It can be applied to other local areas in Thailand that have foreign tourists. A similar training course can be developed by making some modifications to this course to fit their local contents.
Nexus between Gender and Language Shift among the Youth in Nairobi County, Kenya
Authors: Wamaitha Kimani Rosemary , Moraa Nyarigoti Naom , Gatambuki Gathigia Moses
Published: September 2018

The phenomenon of language shift is brought about by language contact. Language shift from mother tongue to another language among the youth is an issue that cannot be wished away due to, inter alia, factors like urbanization, migration, multilingualism or bilingualism and the country’s language policy. Studies have also shown that there is notable difference in the use of language along gender lines. The objective of this study, therefore, is to assess the nexus between the gender variable and language shift among the youth in Nairobi County, Kenya. The study is anchored on a sociolinguistic theory known as the Domain Theory. The study adopted the ex-post facto research design. The study targeted students in public day secondary schools in Nairobi County, Kenya. The sample size of the study comprised 98 students drawn from public day secondary schools in three sub-counties in Nairobi County. Questionnaires were used as the tools of data collection. The reliability of the tool was computed using the Cronbach’s coefficient method with a reliability coefficient of 0.83. Descriptive statistics was used to describe the findings of the data. Chi-square tests were conducted to establish the relationship between gender and language shift. There was a significant relationship (χ2=18.143, p<0.05) between gender and the language used in communication with students of the same sex. There was also a significant relationship (χ2 =13.144, p<0.005) between gender and the language used at school. The findings also show that majority of those who use Kiswahili (62%), Sheng (100%), English and Sheng (100%) or Kiswahili and Sheng (100%) are males. The findings, therefore, show that female and male students use languages differently and therefore, language shift occurred differently between the two genders. The findings, therefore, imply that in schools, female students are more likely to use English while male students are more likely to use Sheng. Kiswahili is used equally among males and females while mother tongue is not used at all. The study concludes that gender plays a significant role in language shift among the youth in Nairobi County. The study recommends that the Ministry of Education reviews the current language policy to include instructions in mother tongue in secondary schools.
An Analysis of English Language Theories: A Case Study
Authors: Alkhaldi Ali Ata , Oshchepkova Tamara
Published: September 2018

Language is implicated in daily lives, and there are a large and open-ended number of activities (Cook, 2003), which involve language theories (Alkhaldi, 2011). This research analyses the language theories which are involved in the activities of Jordanian language materials. The researchers have chosen a sample from language materials used to teach English at Jordanian public high schools since 2015. An analysis checklist has been adapted and used, focusing on the analysis of language theories. The findings show that the students’ role is responsive rather than proactive. The dominant source of content is the materials, and the teachers’ role is overlooked in providing useful language content. Furthermore, the mental operations have not been taken to the deepest level to promote students’ creative and critical thinking skills. The findings also reveal that the materials have a sentence-based content, that is, the content provided as input to learners and content expected as output from the learners comprise individual words, phrases and sentences, and there are few opportunities for extended written and oral discourse. Consequently, it is recommended that teachers, researchers and materials developers should take into consideration such challenging findings to bridge the gap between theory and practice and to develop language materials effectively. In other words, the materials should continuously be analysed, evaluated, and developed in a systematic and rigorous way to have insights into the materials and the process of analysis for professional development purposes, and to help students improve their language learning process.
Semiology of Culture in James Joyce’s A Portrait of the Artist as a Young Man
Authors: Baradaran Jamili Leila , Arshadi Razie
Published: September 2018

This study sheds new light on the role of city whether real or fictional in modern novel as one of the signs of man’s cultural fate. For the same reason, city is not a mere physical place, but a spatial concept. Not only has city become inseparable from man’s personal and national destiny but also one’s life continues to unfold on city’s streets. James Joyce’s (1882-1941) A Portrait of the Artist as a Young Man (A Portrait, 2000) deals with Joyce’s home, Dublin. Joyce aims to universalize and simultaneously eternalize his home through his art. Accordingly, the reader of his text is to decipher the cultural signs of Dublin to get into it. As Michael Ryan (1946-) refers to culture as the total way of life that it has multiple meanings; to understand the culture of a city, to read its meaning, one has to decipher it. Semiology, based on Roland Barthes (1915-1980), is the science of signs whose emphasis is on the interpretation of codes, signs and symbols in a particular culture. Thus, the culture of Dubliners portrayed in A Portrait can be decoded through semiology by the readers. Stephen Dedalus is one who deciphers the cultural signs such as paralysis, religion, prostitution and confession through his walking in Dublin. He considers them as nets of Dublin that he tries to escape from them.
Language Learning Strategy Use and English Proficiency of Iraqi Upper Secondary School Students
Authors: Mahdi Mutar Qusay
Published: September 2018

To learn English language, there are some language-learning strategies, which learners need to be familiar with. Thus, the purpose of this study is to investigate the language learning strategies used among Iraqi sixth-grade preparatory students, and how could gender and proficiency level effect on using language-learning strategies. To analyze the collected data, SPSS software version 20 included Independent sample T-Test Besides, one-way ANOVA and Tukey HSD have been used. A total of 210 sixth-grade preparatory students were chosen randomly from four-different secondary schools for the academic year 2016-2017 at al-Karkh side of Baghdad city. The study sample consisted of (105 females and 105 males). The findings revealed that EFL learners have shown medium use of language learning strategies, besides, no statistically significant differences between male and female students in the frequency of using LLSs. the findings also showed Cognitive and memory strategies were the most frequent used categories comparing to the compensation strategies that scored the least frequent category. As for language proficiency, the result showed that students with high proficiency used all six categories of learning strategies more than medium and low-proficiency students.
Spectral and Dispersion Properties of Long Period Fiber Grating for Optical Communication Systems
Authors: Jain V. , Pawar S. , Kumbhaj S. , Sen P.K.
Published: September 2018

Present work deals with the analytical study of spectral and dispersion properties of long period fiber grating (LPFG) under linear regime. The standard parameters in the understanding of the optical features of an LPFG have been analyzed using the linear coupling processes such that one can appreciate without going through the cumbersome mathematical treatment of coupled mode equations the basic characteristics of the grating. We have analyze transmittance, phase factor, group delay and group velocity dispersion (GVD) of the LPFG as functions of physical parameters like operating wavelength, grating length, induced index change, and detuning parameter. Special attention is paid to the study of GVD with second and third order dispersion contribution as well as the filter characteristics and delay response of the grating. In case of strong grating, we find that at a particular grating strength the resonance band splits into two bands. Negative group delay for certain values of coupling strength suggested that an LPFG can also be used as dispersion compensator in optical fiber communication.
New Compact Wideband Microstrip Antenna for Wireless Applications
Authors: Shandal S. , Mezaal Y. S. , Kadim M. , Mosleh M.
Published: September 2018

In this paper, a miniature rectangular microstrip antenna over partial ground plane is presented by utilizing a space-filling property of fractal geometry in this design. It is simulated by High Frequency Software Simulator (HFSS) software, fabricated and tested by Vector Network Analyzer (VNA).Two types of slots are introduced in order to enhance antenna parameters such as bandwidth and return loss S1.1. This antenna is fabricated on FR4 substrate with a small size of (18 x 16 x 1.5) mm3, 1.5mm substrate thickness, 4.3 permittivity and 0.02 loss tangent. To feed this antenna,  microstrip line feed is used. This antenna is implemented for wide bandwidth (4.8-11.6) GHz, and has three resonant frequencies at 5.5GHz, 8.3GHz and 10.7GHz with impedance bandwidth of 6.8GHz. The gap value g between partial ground plane and rectangular patch at top layer is optimized in order to achieve optimal simulated return loss S1.1 is (-46,-32,-14) dB at three resonant frequencies (5.5, 8.3, 10.7) GHz and optimal radiation efficiency of 93.42% with gain of 3.63dB. The simulated results have tolerable agreement with measured results. This antenna is suitable for wireless computer applications within  C and X band  communications.
Circularly Polarized Split Ring Resonator Loaded Slot Antenna
Authors: Parvathy A. R. , Ajay V. G. , Thomaskutty M.
Published: September 2018

A compact circularly polarized printed slot antenna operating at 2.45 GHz is reported. The antenna consists of a pair of rotated square split ring resonators (SRR) inside a rectangular slot etched on the ground plane of an FR-4 dielectric substrate. A microstrip open-loop feed is etched on the backside of the dielectric substrate to feed the slot and the split ring resonators. The overall size of the antenna is 60x42x1.6 mm3. The measured -10dB impedance bandwidth is 10.48% (2.38-2.64 GHz) and the measured 3dB axial ratio (AR) bandwidth covers the entire impedance bandwidth.
Improving Mental Health Literacy in Post-Secondary Students: Field Testing the Feasibility and Potential Outcomes of a Peer-Led Approach
Authors: Gilham Chris , Austen Erin L. , Wei Yifeng , Kutcher Stanley
Published: September 2018

Transitions (2nd edition) is an evidence-based life-skills resource designed to help post-secondary students transition from high school to college or university. This study was an on-campus evaluation of peer-led seminars of the mental health content from Transitions. A cross-sectional survey was conducted to assess the mental health literacy of three groups of students: master trainers, student trainers, and seminar participants. Post-seminar, there were significant improvements in mental health knowledge and help-seeking, two key components of participants’ mental health literacy. This peer-led approach is a feasible option with the potential to improve student mental health literacy within a short time frame.
Extracellular histones are the ligands for the uptake of exosomes and hydroxyapatite‐nanoparticles by tumor cells via syndecan‐4
Authors: Ochieng Josiah , Nangami Gladys , Sakwe Amos , Rana Tanu , Ingram Shalonda , Goodwin Jeffrey S. , Moye Cierra , Lammers Philip , Adunyah Samuel E.
Published: September 2018

The mechanisms by which exosomes (nano‐vesicular messengers of cells) are taken up by recipient cells are poorly understood. We hypothesized that histones associated with these nanoparticles are the ligands which facilitate their interaction with cell surface syndecan‐4 (SDC4) to mediate their uptake. We show that the incubation with fetuin‐A (exosome‐associated proteins) and histones mediates the uptake of exosomes that are normally not endocytosed. Similarly, hydroxyapatite‐nanoparticles incubated with fetuin‐A and histones (FNH) are internalized by tumor cells, while nanoparticles incubated with fetuin‐A alone (FN) are not. The uptake of exosomes and FNH, both of which move to the perinuclear region of the cell, is attenuated in SDC4‐knockdown cells. Data show that FNH can compete with exosomes for uptake and that both use SDC4 as uptake receptors.
Evaluation of the truebeam machine performance check (MPC): OBI X‐ray tube alignment procedure
Authors: Barnes Michael P. , Pomare Dennis , Menk Frederick W. , Moraro Buiron , Greer Peter B.
Published: September 2018

Alignment of the On‐Board Imager (OBI) X‐ray tube is important for ensuring imaging to treatment isocenter coincidence, which in turn is important for accurate Image Guided Radiotherapy (IGRT). Varian introduced a new X‐ray tube alignment procedure for the TrueBeam linac in software version 2.5 MR2 as part of the machine performance check (MPC) application. This study evaluated the new procedure against conventional methods and examined the clinical significance of X‐ray tube misalignment. Long term stability and short term repeatability of MPC tube alignment was assessed as well as sensitivity of the method to setup error. Standard quality assurance tests expected to be sensitive to tube misalignment were performed before and after tube alignment. These tests included: IsoCal verification; MPC kV imager offset; Winston‐Lutz: kV imaging to treatment/radiation isocenter coincidence; CBCT image QA using the Catphan phantom; and OBI image geometric accuracy and center pixel alignment. Tube alignment measurements were performed with MPC, the two‐plate method, and wire‐on‐faceplate method. The X‐ray tube was then realigned by approximately 1.01 mm in the tangential plane based upon MPC and the tube alignment and standard quality assurance measurements were repeated. The time taken for each tube alignment method was estimated. The MPC method of tube alignment was found to be repeatable, insignificantly sensitive to phantom setup error and quick and simple to perform. The standard QA tests were generally insensitive to the tube alignment change, possibly because of the IsoCal correction. However, reduction in the magnitude of IsoCal correction and MPC kV imager offset was recorded after tube alignment. There was also apparent improvement in CBCT image uniformity. The MPC procedure is recommended for X‐ray tube alignment.
Effect and safety of combination lipid‐lowering therapies based on statin treatment versus statin monotherapies on patients with high risk of cardiovascular events
Authors: Wang Chunli , Wang Fei , Cao Qing , Li Zhen , Huang Liya , Chen Shuyan
Published: September 2018

This study aimed to compare the effect and safety of statin monotherapies and combination therapies on lipid‐lowing therapies. We searched for published randomized controlled trial (RCT) reports of statin monotherapies and combination therapies in patients with high risk of cardiovascular events, and extracted lipid levels to perform meta‐analysis. A total of 12 RCT reports were included in this study. According to the new guidelines (low‐density lipoprotein cholesterol [LDL‐C] < 100 mg/dL, high‐density lipoprotein cholesterol [HDL‐C] > 130 mg/dL), the percent of LDL‐C attaining goals in combination therapy is more than that of monotherapy (risk ratio [RR] = 1.43, 95% confidence interval [CI]: 1.13 to 1.82, P = 0.003), and the percent of LDL‐C and HDL‐C attaining goals in combination therapy is greater than that of monotherapy (RR = 1.43, 95% CI: 1.24 to 1.65, P = 0.000). The changing level of blood lipid had significant statistical difference between the two groups. The degree of blood lipid lowered by combination therapy was larger than in monotherapy (standard mean difference [SMD] = −0.45, 95% CI: −0.75 to −0.14, P = 0.004; SMD = −0.72, 95% CI: 0.04 to 1.39, P = 0.039; and SMD = −0.71, 95% CI: −1.12 to −0.3, P = 0.001 in LDL‐C, HDL‐C, and triglyceride, respectively). The incidence of adverse events was not significantly different between the two groups (RR = 1.15, 95% CI: 0.91 to 1.37, P = 0.096; RR = 1.5, 95% CI: 0.55 to 4.1, P = 0.427; RR = 0.63, 95% CI: 0.33 to 1.24, P = 0.181 in incidence of total adverse events, drug‐related treatment, and myalgia, respectively). Combination therapy can bring better effect in reducing lipid. It does not increase the incidence of adverse events, so it can be used widely and safely.
Melatonin and age‐related cardiovascular diseases
Authors: Zhong Jiayu , Liu Youshuo
Published: September 2018

The pineal gland is a neuroendocrine gland closely related to human aging. Melatonin is a kind of indole neuroendocrine hormone secreted by the pineal gland, which is essential for maintaining physiological function. Many researches found that melatonin plays a key role in anti‐aging‐related cardiovascular diseases. In this paper, the latest advances in the study of melatonin and aging‐related cardiovascular diseases are reviewed, and their related physiological functions and mechanisms are discussed.
Neurotoxicity after CTL019 in a pediatric and young adult cohort
Authors: Gofshteyn Jacqueline S. , Shaw Pamela A. , Teachey David T. , Grupp Stephan A. , Maude Shannon , Banwell Brenda , Chen Fang , Lacey Simon F. , Melenhorst Jan J. , Edmonson MacKenzie J. , Panzer Jessica , Barrett David M. , McGuire Jennifer L.
Published: September 2018

Objective

To characterize the incidence and clinical characteristics of neurotoxicity in the month following CTL019 infusion in children and young adults, to define the relationship between neurotoxicity and cytokine release syndrome (CRS), and to identify predictive biomarkers for development of neurotoxicity following CTL019 infusion.

Methods

We analyzed data on 51 subjects, 4 to 22 years old, who received CTL019, a chimeric antigen receptor–modified T‐cell therapy against CD19, between January 1, 2010 and December 1, 2015 through a safety/feasibility clinical trial (NCT01626495) at our institution. We recorded incidence of significant neurotoxicity (encephalopathy, seizures, and focal deficits) and CRS, and compared serum cytokine levels in the first month postinfusion between subjects who did and did not develop neurotoxicity.

Results

Neurotoxicity occurred in 23 of 51 subjects (45%, 95% confidence interval = 31–60%) and was positively associated with higher CRS grade (p < 0.0001) but was not associated with demographic characteristics or prior oncologic treatment history. Serum interleukin (IL)‐2, IL‐15, soluble IL‐4, and hepatocyte growth factor concentrations were higher in subjects with neurotoxicity than those with isolated CRS. Differences in peak levels of select cytokines including IL‐12 and soluble tumor necrosis factor receptor‐1 within the first 3 days were seen in subjects with neurotoxicity.

Interpretation

Neurotoxicity is common after CTL019 infusion in children and young adults, and is associated with higher CRS grade. Differences in serum cytokine profiles between subjects with neurotoxicity and those with isolated CRS suggest unique pathophysiological mechanisms. Serum cytokine profiles in the first 3 days postinfusion may help identify children and young adults at risk for neurotoxicity, and may provide a foundation for investigation into potential mitigation strategies. Ann Neurol 2018;84:537–546
Expanded disability status scale progression assessment heterogeneity in multiple sclerosis according to geographical areas
Authors: Bovis Francesca , Signori Alessio , Carmisciano Luca , Maietta Ilaria , Steinerman Joshua R. , Li Thomas , Tansy Aaron P. , Sormani Maria Pia
Published: September 2018

Using placebo data from 3 randomized multiple sclerosis (MS) trials with uniform inclusion criteria, we investigated heterogeneity of Expanded Disability Status Scale (EDSS) progression by geographical areas. Our analysis revealed a significantly lower EDSS progression in Eastern European countries (10.8%) compared with Western Europe (13.1%) or the USA/Canada (21.4%, p < 0.001); EDSS improvement behaved the same way. This heterogeneity is not explained by differences of baseline variables. No differences were detected on more easily quantifiable measures, the Timed 25‐Foot Walk or the Multiple Sclerosis Functional Composite. At a time when disease progression represents the target for future interventions in MS, establishment of more quantitative and objective outcomes remains a key priority of MS research. Ann Neurol 2018;84:621–625
Low‐voltage fast seizures in humans begin with increased interneuron firing
Authors: Elahian Bahareh , Lado Nathan E. , Mankin Emily , Vangala Sitaram , Misra Amrit , Moxon Karen , Fried Itzhak , Sharan Ashwini , Yeasin Mohammed , Staba Richard , Bragin Anatol , Avoli Massimo , Sperling Michael R. , Engel Jerome , Weiss Shennan A.
Published: September 2018

Objective

Intracellular recordings from cells in entorhinal cortex tissue slices show that low‐voltage fast (LVF) onset seizures are generated by inhibitory events. Here, we determined whether increased firing of interneurons occurs at the onset of spontaneous mesial–temporal LVF seizures recorded in patients.

Methods

The seizure onset zone (SOZ) was identified using visual inspection of the intracranial electroencephalogram. We used wavelet clustering and temporal autocorrelations to characterize changes in single‐unit activity during the onset of LVF seizures recorded from microelectrodes in mesial–temporal structures. Action potentials generated by principal neurons and interneurons (ie, putative excitatory and inhibitory neurons) were distinguished using waveform morphology and K‐means clustering.

Results

From a total of 200 implanted microelectrodes in 9 patients during 13 seizures, we isolated 202 single units; 140 (69.3%) of these units were located in the SOZ, and 40 (28.57%) of them were classified as inhibitory. The waveforms of both excitatory and inhibitory units remained stable during the LVF epoch (p > > 0.05). In the mesial–temporal SOZ, inhibitory interneurons increased their firing rate during LVF seizure onset (p < 0.01). Excitatory neuron firing rates peaked 10 seconds after the inhibitory neurons (p < 0.01). During LVF spread to the contralateral mesial temporal lobe, an increase in inhibitory neuron firing rate was also observed (p < 0.01).

Interpretation

Our results suggest that seizure generation and spread during spontaneous mesial–temporal LVF onset events in humans may result from increased inhibitory neuron firing that spawns a subsequent increase in excitatory neuron firing and seizure evolution. Ann Neurol 2018;84:588–600
Facioscapulohumeral Dystrophy in Childhood: A Nationwide Natural History Study
Authors: Goselink Rianne J.M. , Schreuder Tim H.A. , van Alfen Nens , de Groot Imelda J.M. , Jansen Merel , Lemmers Richard J.L.F. , van der Vliet Patrick J. , van der Stoep Nienke , Theelen Thomas , Voermans Nicol C. , van der Maarel Silvère M. , van Engelen Baziel G.M. , Erasmus Corrie E.
Published: September 2018

Objective

Facioscapulohumeral dystrophy (FSHD) is one of the most frequent heritable muscular dystrophies, with a large variety in age at onset and disease severity. The natural history and molecular characteristics of FSHD in childhood are incompletely understood. Our objective is to clinically and genetically characterize FSHD in childhood.

Methods

We performed a nationwide, single‐investigator, natural history study on FSHD in childhood.

Results

Multiple‐source recruitment resulted in 32 patients with FSHD (0–17 years), leading to an estimated prevalence of 1 in 100,000 children in The Netherlands. This series of 32 children with FSHD revealed a heterogeneous phenotype and genotype in childhood. The phenotypic hallmarks of FSHD in childhood are: facial weakness with normal or only mildly affected motor performance, decreased functional exercise capacity (6‐minute walk test), lumbar hyperlordosis, and increased echo intensity on muscle ultrasonography. In addition, pain and fatigue were frequent and patients experienced a lower quality of life compared to healthy peers. In contrast to the literature on early‐onset FSHD, systemic features such as hearing loss and retinal and cardiac abnormalities were infrequent and subclinical, and epilepsy and intellectual disability were absent. Genotypically, patients had a mean D4Z4 repeat array of 5 units (range, 2–9), and 14% of the mutations were de novo.

Interpretation

FSHD in childhood is more prevalent than previously known and the genotype resembles classic FSHD. Importantly, FSHD mainly affects functional exercise capacity and quality of life in children. As such, these results are paramount for counseling, clinical management, and stratification in clinical research. Ann Neurol 2018;84:635–645
Zirconium‐assistierte Aktivierung von Palladium zur Steigerung der Produktion von Synthesegas in der Trockenreformierung von Methan
Authors: Köpfle Norbert , Götsch Thomas , Grünbacher Matthias , Carbonio Emilia A. , Hävecker Michael , Knop‐Gericke Axel , Schlicker Lukas , Doran Andrew , Kober Delf , Gurlo Aleksander , Penner Simon , Klötzer Bernhard
Published: September 2018

Kohlenstoff‐gesättigte Pd0‐Nanopartikel mit ausgedehnter Phasengrenze zu ZrO2 bilden sich unter CH4‐Trockenreformierbedingungen aus einem intermetallischen Pd0Zr0‐Präkatalysator. Der resultierende, hochaktive Katalysatorzustand arbeitet bifunktionell: CO2 wird an oxidischen Phasengrenzplätzen effizient aktiviert, und PdxC gewährleistet die rasche Versorgung der Phasengrenze mit reaktiven C‐Atomen.
Active Sites on Nickel‐Promoted Transition‐Metal Sulfides That Catalyze Hydrogenation of Aromatic Compounds
Authors: Luo Wanqiu , Shi Hui , Schachtl Eva , Gutiérrez Oliver Y. , Lercher Johannes A.
Published: September 2018

Hydrogenation on Mo and W sulfides occurs at the edges of the sulfide slabs. The rate of hydrogen addition is directly proportional to the concentration of sulfhydryl (SH) groups at the slab edge and the metal atom attached to it. Sulfhydryl groups vicinal to edge‐incorporated Ni hydrogenate with much higher rates than SH close to Mo and W. Each subset of SH groups, however, exhibits nearly identical intrinsic activity and selectivity, independent of the sulfide composition. The higher activity of Ni‐WS2 compared to Ni‐MoS2 stems from a higher concentration of SH groups on the former sulfide associated with a higher tendency of its surface vacancies to react with H2.
Antibody–Drug Conjugates with Pyrrole‐Based KSP Inhibitors as the Payload Class
Authors: Lerchen Hans‐Georg , Wittrock Sven , Stelte‐Ludwig Beatrix , Sommer Anette , Berndt Sandra , Griebenow Nils , Rebstock Anne‐Sophie , Johannes Sarah , Cancho‐Grande Yolanda , Mahlert Christoph , Greven Simone , Terjung Carsten
Published: September 2018

The number of cytotoxic payload classes successfully employed in antibody–drug conjugates (ADCs) is still rather limited. The identification of ADC payloads with a novel mode of action will increase therapeutic options and potentially increase the therapeutic window. Herein, we describe the utilization of kinesin spindle protein inhibitors (KSPi) as a novel payload class providing highly potent ADCs against different targets, for instance HER‐2 or TWEAKR/Fn14. Aspects of technical optimization include the development of different linker attachment sites, the stabilization of ADC linkage to avoid payload deconjugation and finally, the tailor‐made design of active metabolites with a long lasting intracellular exposure in the tumor matching the mode of action of KSP inhibition. These KSPi‐ADCs are highly potent and selective in vitro and demonstrate in vivo efficacy in a broad panel of tumor models including complete regressions in a patient‐derived urothelial cancer model.
Human Brain Project: Ethics Management statt Prozeduralisierung von Reflexivität?
Authors: Maasen Sabine
Published: September 2018

Human Brain Project: Ethics Management or Proceduralization of Reflexivity? Everywhere, the reflexivity and responsibility of research and innovation is called for – the neurosciences being no exception. Undesirable side effects of scientific‐technical developments should be recognized early on and opportunities for participation by non‐scientific actors should be made available. In addition to the well‐known reflective programs such as Technology Assessment, Public Understanding of Science, Ethical Legal and Social Implications (ELSI) of Science, Science Communication and Citizen Science, a new program is emerging: Responsible Research and Innovation (RRI). With the dimensions of anticipation, reflexivity, inclusiveness and responsiveness advocated here, social accountability of research has just been expanded again: factually (applying to the scientific practice of all domains), temporally (becoming more and more permanent) and socially (involving more and more actors). The following study will first reconstruct the current prominence of RRI as the dynamics of a changing relationship between science and society, then explore into the claim and reality of RRI as documented in publicly available material. The observation: While RRI at the level of its program aims at legitimacy through democratization of knowledge production, the organization of RRI demonstrates highly orchestrated bureaucratic arrangements and procedures. In the case of the Human Brain Project, it thus becomes clear that and how RRI is being put to the service of supporting neuroinformatic big science through targeted reductions: it is mainly framed as ‘ethics management’ and hardly integrated into research practice or even public discourse.
Antitumor activity of NAX060: A novel semisynthetic berberine derivative in breast cancer cells
Authors: Pierpaoli Elisa , Fiorillo Gaetano , Lombardi Paolo , Salvatore Carmela , Geroni Cristina , Piacenza Francesco , Provinciali Mauro
Published: September 2018

Breast cancer (BC) is the most common malignancy and the most common cause of cancer death in elderly women. We recently demonstrated that innovative compounds structurally related to and semisynthetically derived from the plant alkaloid berberine represent a promising unexplored resource for novel therapeutic tools in BC therapy. In this study, we analyzed the effectiveness of new 13‐dichlorophenylalkyl berberine semisynthetic derivatives (NAX060, NAX103, NAX111, and NAX114) on the viability of BC cell lines. Our results demonstrated that the new compounds effectively inhibited the growth of a variety of human BC cell lines. In particular, the viability of HER‐2 overexpressing SK‐BR‐3 cells was significantly reduced by the treatment with NAX060, the most active compound, in a dose and time‐dependent manner. In the same tumor cell line, NAX060 induced a strong increase in sub‐G1 population while G0/G1 and G2/M phase cells remarkably decreased. NAX060 withdrawal after 72 h of treatment resulted in an irreversible cell proliferation arrest and increasing cell death. Real‐time PCR analyses showed that NAX060 induced the expression of some cell‐cycle checkpoint molecules involved in cell senescence such as p21WAF1, p27, p16INK4a, and PAI‐1. Furthermore, the HER‐2 protein expression and phosphorylation, as well as the level of heparanase expression, were remarkably reduced on SK‐BR‐3 cells. NAX060 was effective also on HER‐2 negative tumor cells, and, in particular, on human triple‐negative MDA‐MB‐231 cells. These data suggest a potential therapeutic effect of NAX060 compound in the management of BC malignancies. Interestingly, NAX060 may represent a new useful tool also in triple‐negative BC. © 2018 BioFactors, 44(5):443–452, 2018