bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined BRAF and HSP90 Inhibition in Patients with Unresectable BRAFV600E-Mutant Melanoma
Authors: Eroglu Zeynep , Chen Y. Ann , Gibney Geoffrey T. , Weber Jeffrey S. , Kudchadkar Ragini R. , Khushalani Nikhil I. , Markowitz Joseph , Brohl Andrew S. , Tetteh Leticia F. , Ramadan Howida , Arnone Gina , Li Jiannong , Zhao Xiuhua , Sharma Ritin , Darville Lancia N.F. , Fang Bin , Smalley Inna , Messina Jane L. , Koomen John M. , Sondak Vernon K. , Smalley Keiran S.M.
Published: April 2018

Purpose: BRAF inhibitors are clinically active in patients with advanced BRAFV600-mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888.

Patients and Methods: Vemurafenib (960 mg p.o. b.i.d.) combined with escalating doses of XL888 (30, 45, 90, or 135 mg p.o. twice weekly) was investigated in 21 patients with advanced BRAFV600-mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity.

Results: Objective responses were observed in 15 of 20 evaluable patients [75%; 95% confidence interval (CI), 51%–91%], with 3 complete and 12 partial responses. Median progression-free survival and overall survival were 9.2 months (95% CI, 3.8–not reached) and 34.6 months (6.2–not reached), respectively. The most common grade 3/4 toxicities were skin toxicities, such as rash (n = 4, 19%) and cutaneous squamous cell carcinomas (n = 3, 14%), along with diarrhea (n = 3, 14%). Pharmacodynamic analysis of patients' peripheral blood mononuclear cells (PBMC) showed increased day 8 HSP70 expression compared with baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy.

Conclusions: XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAFV600-mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAFV600-mutant melanoma. Clin Cancer Res; 24(22); 5516–24. ©2018 AACR.

See related commentary by Sullivan, p. 5496
Antigen Presentation Keeps Trending in Immunotherapy Resistance
Authors: Kalbasi Anusha , Ribas Antoni
Published: April 2018

Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T-cell immunotherapy not previously identified using CRISPR-based screens. MEX3B is a posttranscriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T-cell immunotherapy and indicating a new putative molecular target. Clin Cancer Res; 24(14); 3239–41. ©2018 AACR.

See related article by Huang et al., p. 3366
Tamoxifen Resistance Trumped and Oral Selective Estrogen Receptor Degraders Arrive
Authors: Jordan V. Craig
Published: April 2018

Predictive tests, to refine the estrogen receptor assay, for the adjuvant treatment of breast cancer with tamoxifen and oral selective estrogen receptor degraders (SERD) are required. A splice variant of the corepressor NCOR2, BQ2313636.1 predicts tamoxifen resistance to adjuvant tamoxifen and AZ9496, the first oral SERD, completes phase I studies. Clin Cancer Res; 24(15); 3480–2. ©2018 AACR.

See related articles by Gong et al., p. 3681 and Hamilton et al., p. 3510
Initial Management of Colonic Diverticular Bleeding: Observational Study
Authors: Wada Michiko , Kato Motohiko , Hirai Yuichiro , Kubosawa Yoko , Sunata Yukie , Abe Keiichiro , Hirata Tetsu , Takada Yoshiaki , Banno Shigeo , Takatori Yusaku , Kinoshita Satoshi , Mori Hideki , Takabayashi Kaoru , Kikuchi Miho , Kikuchi Masahiro , Suzuki Masayuki , Kanai Takanori , Uraoka Toshio
Published: April 2018

Background/Aims: Although colonic diverticular bleeding (CDB) often ceases spontaneously, re-bleeding occurs in about 30%. Bleeding diverticulum can be treated directly by endoscopic hemostasis; however, it is difficult to perform colonoscopy in all cases with limited medical resource and certain risks. The aim of this study was to clarify who should undergo colonoscopy as well as appropriate methods of initial management in CDB patients. Methods: A total of 285 patients who were diagnosed as CDB and underwent colonoscopy from March 2004 to October 2015 were retrospectively analyzed. First, the association between re-bleeding and various factors including patients’ background and initial management were analyzed. Second, the examination conditions that influenced bleeding point identification were analyzed. Results: Of 285 patients, 187 were men and 98 were women. Median age was 75 years, and the median observation period was 17.5 months. Re-bleeding was observed in 79 patients (28%). A history of CDB (OR 2.1, p = 0.0090) and chronic kidney disease (CKD; OR 2.3, p = 0.035) were risk factors, and bleeding point identification (OR 0.20, p = 0.0037) was a preventive factor for re-bleeding. Bleeding point identification significantly reduced approximately 80% of re-bleeding. Furthermore, extravasation on CT (OR 3.7, p = 0.031) and urgent colonoscopy (OR 5.3, p < 0.001) were predictors for identification of bleeding point. Compared to bleeding point identification of 11% in all patients who underwent colonoscopy, identification rate in those who had extravasation on CT and underwent urgent colonoscopy was as high as 70%. Conclusions: Contrast-enhanced CT upon arrival is suggested, and patients with extravasation on CT would be good candidates for urgent colonoscopy, as well as patients who have a history of CDB and CKD.
Sodium and Potassium Content of Meals Served in University Canteens
Authors: Barbosa Maria Inês , Fernandes Alexandra , Gonçalves Carla , Pena Maria João , Padrão Patrícia , Pinho Olívia , Moreira Pedro
Published: April 2018

A high sodium intake is associated with high blood pressure, an important risk factor for noncommunicable diseases (NCDs). In contrast, the ingestion of high levels of potassium counteracts this negative effect of high sodium intake on blood pressure, thus reducing the sodium-to-potassium ratio. The aim of this work was to determine the sodium and potassium content of meals served in university canteens in Portugal. The analysis included 35 samples of soup and 35 samples of main dish collected at 5 random days from a total of 7 university canteens. The samples were analyzed for sodium and potassium by atomic emission spectrometry technique. On average, a meal (soup and main dish) had a sodium content of 1,069.4 mg (mean sodium content was 671.4 ± 374.5 mg/portion in the main dish and 398.0 ± 153.0 mg/portion in the soup) and a potassium content of 1,004 mg (mean potassium content was 731.4 ± 385.9 mg/serving in the main dish and 272.6 ± 272.6 mg/serving in the soup). Our results revealed that with a single university meal, students can reach 53% of the maximum daily value recommended for sodium and 27% of the minimum daily value recommended for potassium. An investment to decrease sodium and increase potassium in meals served is imperative in order to prevent NCDs.
Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells
Authors: Sandbichler Adolf M. , Jansen Bianca , Peer Bettina A. , Paulitsch Monika , Pelster Bernd , Egg Margit
Published: April 2018

Background/Aims: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. Methods: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Results: Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly oxidized nocturnal cellular environment. Of note, circadian rhythms of cytosolic H2O2 remain unaltered, while the transcriptional clock is already attenuated, as it is known to occur also under chronic hypoxia. Conclusion: We therefor propose that the realignment of metabolic redox oscillations might initiate the observed hypoxia induced attenuation of the transcriptional clock, based on the reduced binding affinity of the CLOCK/BMAL complex to the DNA in an oxidized environment.
Intermittent Hypoxia Inhibits Na+-H+ Exchange-Mediated Acid Extrusion Via Intracellular Na+ Accumulation in Cardiomyocytes
Authors: Chang Huai-Ren , Lien Chih-Feng , Jeng Jing-Ren , Hsieh Jen-Che , Chang Chen-Wei , Lin Jian-Hong , Yang Kun-Ta
Published: April 2018

Background/Aims: Intermittent hypoxia (IH) has been shown to exert preconditioning-like cardioprotective effects. It also has been reported that IH preserves intracellular pH (pHi) during ischemia and protects cardiomyocytes against ischemic reperfusion injury. However, the exact mechanism is still unclear. Methods: In this study, we used proton indicator BCECF-AM to analyze the rate of pHi recovery from acidosis in the IH model of rat neonatal cardiomyocytes. Neonatal cardiomyocytes were first treated with repetitive hypoxia-normoxia cycles for 1-4 days. Cells were then acid loaded with NH4Cl, and the rate of pHi recovery from acidosis was measured. Results: We found that the pHi recovery rate from acidosis was much slower in the IH group than in the room air (RA) group. When we treated cardiomyocytes with Na+-H+ exchange (NHE) inhibitors (Amiloride and HOE642) or Na+-free Tyrode solution during the recovery, there was no difference between RA and IH groups. We also found intracellular Na+ concentration ([Na+]i) significantly increased after IH exposure for 4 days. However, the phenomenon could be abolished by pretreatment with ROS inhibitors (SOD and phenanathroline), intracellular calcium chelator or Na+-Ca2+ exchange (NCX) inhibitor. Furthermore, the pHi recovery rate from acidosis became faster in the IH group than in the RA group when inhibition of NCX activity. Conclusions: These results suggest that IH would induce the elevation of ROS production. ROS then activates Ca2+-efflux mode of NCX and results in intracellular Na+ accumulation. The rise of [Na+]i further inhibits the activity of NHE-mediated acid extrusion and retards the rate of pHi recovery from acidosis during IH.
Risk of Infective Endocarditis After Invasive Dental Treatments
Authors: Chen Tzu-Ting , Yeh Yi-Chun , Chien Kuo-Liong , Lai Mei-Shu , Tu Yu-Kang
Published: April 2018

Background:

Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE.

Methods:

The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT.

Results:

In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94–1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02–1.26) for 1 to 4 weeks after IDTs.

Conclusions:

In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.
Did they Define the Outcome? Churches and the Independence Referendum in Scotland
Authors: Mudrov Sergei A.
Published: April 2018

The 2014 referendum in Scotland, which brought victory for the unionists, was characterised by a high level of involvement of religious organisations in the campaign. Although the Churches chose to be neutral on the referendum dilemma, this was explained by prevailing attitudes among clergy, who objected Scottish independence. In this article, analysing the stance of the Church of Scotland, Roman Catholic Church, Episcopal Church of Scotland, and Free Church of Scotland, I argue that the chosen path of neutrality played more in favour of unionists. The Churches’ influence on the referendum’s outcome was far beyond statistical errors, and had Churches publicly supported independence, it would have been likely that Edinburgh would now be negotiating the terms of “divorce” with London.
An annotated checklist of the chondrichthyans of Papua New Guinea
Authors: WHITE WILLIAM T. , KO’OU ALFRED
Published: April 2018

An annotated checklist of the chondrichthyan fishes (sharks, rays, and chimaeras) of Papua New Guinean waters is herein presented. The checklist is the result of a large biodiversity study on the chondrichthyan fauna of Papua New Guinea between 2013 and 2017. The chondrichthyan fauna of Papua New Guinea has historically been very poorly known due to a lack of baseline information and limited deepwater exploration. A total of 131 species, comprising 36 families and 68 genera, were recorded. The most speciose families are the Carcharhinidae with 29 species and the Dasyatidae with 23 species. Verified voucher material from various biological collections around the world are provided, with a total of 687 lots recorded comprising 574 whole specimens, 128 sets of jaws and 21 sawfish rostra. This represents the first detailed, verified checklist of chondrichthyans from Papua New Guinean waters.
Annotated catalogue of the click-beetle tribe Dimini (Coleoptera: Elateridae: Dendrometrinae)
Authors: KUNDRATA ROBIN , MUSALKOVA MARKETA , KUBACZKOVA MAGDALENA
Published: April 2018

An annotated catalogue of the tribe Dimini (Coleoptera: Elateridae: Dendrometrinae) is presented. Altogether, 273 extant species are classified in 11 genera: Brancuccia Schimmel & Platia, 1991 (eight species), Csikia Szombathy, 1910 (eight spp.), Dima Charpentier, 1825 (77 spp.), Neocsikia Ôhira & Becker, 1972 (two spp.), Neodima Schimmel & Platia, 1992a (two spp.), Paracsikia Schimmel & Platia, 1991 (seven spp.), Parapenia Suzuki, 1982b (14 spp.), Penia Laporte, 1838 (108 spp.), Platiana Schimmel, 1993 (34 spp.), Pseudocsikia Schimmel & Platia, 1991 (10 spp.), and Sabahdima Schimmel & Platia, 1993 (three spp.). The only fossil genus included in this tribe is monotypic Alaodima Dolin, 1980. Dimini are distributed in the Palaearctic and Oriental Regions. For each taxon we provide synonyms, information on types, type localities, distribution, and bibliography. The lectotype of Penia apicalis Fleutiaux, 1936 is here designated in order to fix the identity of the species for future studies. Penia impressifrons Schimmel, 1993 from Vietnam is synonymized with Ceroleptus sulcatus (Fleutiaux, 1903), a representative of Elateridae: Oxynopterinae.
Contrasting Impacts of Radiative Forcing in the Southern Ocean versus Southern Tropics on ITCZ Position and Energy Transport in One GFDL Climate Model
Authors: Xiang Baoqiang , Zhao Ming , Ming Yi , Yu Weidong , Kang Sarah M.
Published: April 2018

Most current climate models suffer from pronounced cloud and radiation biases in the Southern Ocean (SO) and in the tropics. Using one GFDL climate model, this study investigates the migration of the intertropical convergence zone (ITCZ) with prescribed top-of-the-atmosphere (TOA) shortwave radiative heating in the SO (50°–80°S) versus the southern tropics (ST; 0°–20°S). Results demonstrate that the ITCZ position response to the ST forcing is twice as strong as the SO forcing, which is primarily driven by the contrasting sea surface temperature (SST) gradient over the tropics; however, the mechanism for the formation of the SST pattern remains elusive. Energy budget analysis reveals that the conventional energetic constraint framework is inadequate in explaining the ITCZ shift in these two perturbed experiments. For both cases, the anomalous Hadley circulation does not contribute to transport the imposed energy from the Southern Hemisphere to the Northern Hemisphere, given a positive mean gross moist stability in the equatorial region. Changes in the cross-equatorial atmospheric energy are primarily transported by atmospheric transient eddies when the anomalous ITCZ shift is most pronounced during December–May. The partitioning of energy transport between the atmosphere and ocean shows latitudinal dependence: the atmosphere and ocean play an overall equivalent role in transporting the imposed energy for the extratropical SO forcing, while for the ST forcing, the imposed energy is nearly completely transported by the atmosphere. This contrast originates from the different ocean heat uptake and also the different meridional scale of the anomalous ocean circulation.
Early-life Medicaid Coverage and Intergenerational Economic Mobility
Authors: O’Brien Rourke L. , Robertson Cassandra L.
Published: April 2018

New data reveal significant variation in economic mobility outcomes across U.S. localities. This suggests that social structures, institutions, and public policies—particularly those that influence critical early-life environments—play an important role in shaping mobility processes. Using new county-level estimates of intergenerational economic mobility for children born between 1980 and 1986, we exploit the uneven expansions of Medicaid eligibility across states to isolate the causal effect of this specific policy change on mobility outcomes. Instrumental-variable regression models reveal that increasing the proportion of low-income pregnant women eligible for Medicaid improved the mobility outcomes of their children in adulthood. We find no evidence that Medicaid coverage in later childhood years influences mobility outcomes. This study has implications for the normative evaluation of this policy intervention as well as our understanding of mobility processes in an era of rising inequality.
Days of rage
Authors: Chenoweth Erica , Pinckney Jonathan , Lewis Orion
Published: April 2018

Although the empirical study of strategic nonviolent action has expanded in recent years, no current dataset provides detailed accounts of the day-to-day methods and tactics used by various nonviolent and violent actors seeking political change. We introduce the Nonviolent and Violent Campaigns and Outcomes (NAVCO) version 3.0 dataset, which assembles over 100,000 hand-coded observations of nonviolent and violent methods in 21 countries around the world between 1991 and 2012. Researchers can use these data and their associated coding framework to (1) replicate or challenge existing findings about nonviolent and violent action; (2) test or uncover novel insights about the dynamics of violent and nonviolent action; and (3) recode existing protest events databases to capture specific variations in risk and disruption across event types. In particular, scholars can use these data to better understand which types of lower-level interactions between dissidents and regimes lead to large-scale mobilization; which sequences of nonviolent methods are most effective; and which types of spatial and participation diffusion yield the highest likelihood of success.
A comprehensive decoupling active disturbance rejection control for a gas flow facility
Authors: Sun Lijun , Zhao Yue , Wu Xia , Chen Zengqiang
Published: April 2018

Based on the linear active disturbance rejection control (LADRC), a comprehensive decoupling controller for gas flow facilities is presented to guarantee stability and a fast response during the process of gas flowmeter performance tests. First, a mathematical model is developed to describe the pressure-flow coupling system. Then, a step response method is applied to identify parameters of this model. To realize the effective decoupling control, the static coupling part is introduced into the LADRC design. The overall effect of the dynamic coupling part among two channels, the internal uncertainties and the external disturbance, are treated as total disturbance, which is estimated using the extended state observer and cancelled out by the control law. After estimating and cancelling, the pressure-flow coupling system can be transformed into two single input single output subsystems with the form of cascade integrators. Then two proportional differential controllers are applied to control the two simplified subsystems. Simulation and experimental results show that the proposed algorithm has a shorter settling time, a more effective decoupling effect and a greater capability of disturbance rejecting and stronger performance robustness in gas flow facility than conventional proportional–integral–derivative algorithms.
Robust spacecraft attitude tracking control with integral terminal sliding mode surface considering input saturation
Authors: Chen Haitao , Song Shenmin , Li Xuehui
Published: April 2018

This paper studies the finite time spacecraft attitude tracking control problem, while considering modeling uncertainty, external disturbances and control input saturation. A novel integral terminal sliding mode surface (ITSMS) is designed by combining the fast terminal sliding mode surface (FTSMS) with a low pass filter to achieve a fast finite time convergence rate for the control system, without input singularity. An auxiliary signal is used to compensate for the effects of actuator saturation. The basic controller is first formulated based on the ITSMS, fast-TSM-type reaching law and auxiliary system, in the presence of an external disturbance and input saturation. Then, an adaptive control procedure is introduced, which simultaneously handles modeling uncertainty and external disturbance, thereby creating an adaptive attitude tracking controller. The proposed controller provides a fast finite time convergence rate for the control system, based on the newly designed ITSMS, while simultaneously compensating for modeling uncertainty, external disturbances and input saturation, without restricting the parameter selection process nor requiring repeated differentiation of nonlinear functions. Finally, digital simulation results are presented and demonstrate the effectiveness of the proposed controllers.
Investigating the Pricing Impacts of the American Airlines and US Airways Merger
Authors: Zhang Yunzhou , Nozick Linda
Published: April 2018

In 2013, American Airlines merged with US Airways creating the largest airline in the world. This paper analyzes this merger’s effect on domestic airline ticket pricing using the Department of Transportation’s 10% ticket sample. This analysis confirmed insights that have been identified in prior analyses including in which there is heightened competition, prices are lower. It also demonstrates again that mergers can be correlated with rising prices. What is perhaps novel is that although legacy carriers generally increased prices post-merger, low-cost carriers did not appear to have that same freedom. Rather, they lowered prices, and those fare reductions were largest in markets for which American Airlines and US Airways played a larger role pre-merger.
Diagnostic value of complete blood count in paraquat and organophosphorus poisoning patients
Authors: Tang Yahui , Hu Lufeng , Hong Guangliang , Zhong Dahai , Song Jiaxing , Zhao Guangju , Lu Zhongqiu
Published: April 2018

Complete blood count (CBC) is one of the most extensively used tests in clinical practice. In order to determine the diagnostic value of the CBC in paraquat (PQ) and organophosphorus (OPPs) poisoning, the CBC indices of PQ- and OPPs-poisoned patients were investigated in this study. A total of 96 PQ poisoning patients, 90 OPPs poisoning patients, and 188 healthy subjects were included in this study. The PQ- and OPPs-poisoned patients were divided into different groups according to their clinical symptoms. All CBC indices were analyzed by Fisher discriminant, partial least-squares discriminant analysis (PLS-DA), variance analysis, and receiver operating characteristic (ROC). The discriminant results showed that 87.7% of original grouped cases correctly classified between PQ-poisoned patients, OPPs-poisoned patients, and healthy subjects. The PLS-DA results showed that the important variable order was different in PQ- and OPPs-poisoned patients. Both white blood cell (WBC) and neutrophil (NE) counts were the most important indexes in PQ- and OPPs-poisoned patients. In OPPs poisoning patients, WBC and NE showed statistical differences between the severe poisoning group and the moderate poisoning group. Their areas under the ROC curve (AUC) were 0.673 (WBC) and 0.669 (NE), which were higher than cholinesterase (CHE; AUC 0.326). In conclusion, the CBC indices had a diagnostic value in PQ and OPPs poisoning; WBC and NE were the first responses and had clinical significance in PQ and OPPs poisoning; moreover, they are better than CHE in diagnosing OPPs poisoning.
Regulation of the Neuroligin-1 Gene by Clock Transcription Factors
Authors: Hannou Lydia , Bélanger-Nelson Erika , O’Callaghan Emma K. , Dufort-Gervais Julien , Ballester Roig Maria Neus , Roy Pierre-Gabriel , Beaulieu Jean-Martin , Cermakian Nicolas , Mongrain Valérie
Published: April 2018

NEUROLIGIN-1 (NLGN1) is a postsynaptic adhesion molecule involved in the regulation of glutamatergic transmission. It has been associated with several features of sleep and psychiatric disorders. Our previous work suggested that transcription of the Nlgn1 gene could be regulated by the transcription factors CLOCK and BMAL1 because they bind to the Nlgn1 gene promoter in vivo. However, whether CLOCK/BMAL1 can directly activate Nlgn1 transcription is not yet known. We thus aimed to verify whether CLOCK/BMAL1, as well as their homologs NPAS2 and BMAL2, can activate transcription via the Nlgn1 promoter by using luciferase assays in COS-7 cells. We also investigated how Nlgn1 expression was affected in Clock mutant mice. Our results show transcriptional activation in vitro mediated by CLOCK/BMAL1 and by combinations with their homologs NPAS2 and BMAL2. Moreover, CLOCK/BMAL1 activation via the Nlgn1 gene fragment was repressed by GSK3β. In vivo, Nlgn1 mRNA expression was significantly modified in the forebrain of Clock mutant mice in a transcript variant–dependent manner. However, no significant change in NLGN1 protein level was observed in Clock mutant mice. These findings will increase knowledge about the transcriptional regulation of Nlgn1 and the relationship between circadian rhythms, mental health, and sleep.
Visceral politics across the Strait: Food and risk in China–Taiwan relations
Authors: Kan Karita , Yuen Samson
Published: April 2018

The globalization of food systems has led to the increased circulation of food risks across national boundaries. While there is a rich literature on the domestic risk politics of food safety in China, much less attention has been given to the external dimension of China’s food safety issues and how these interplay with relations in the international arena. This article examines the visceral politics of food and risk in China–Taiwan relations. Drawing on the scandal of the export of tainted milk products from China to Taiwan in 2008 and the ongoing food safety debates surrounding the implementation of the Cross-Strait Economic Cooperation Framework Agreement, we argue that perceptions of and responses to food risks cannot be considered in isolation from the political, economic and social context of cross-strait relations where different state, societal and media actors interact in the construction of risks. Rather than being a purely technical matter of safety assessment, the identification, representation and management of food risks are shown to be a social process that is contested at all times.
Three-directional contact force model for the ball spinning of a thin-walled tube
Authors: Zhao Chun-jiang , Su Meng-ying , Jiang Zheng-yi , Lian-yun Jiang , Yang Xiaorong , Cui Hai-long
Published: April 2018

This paper provides a computational model for calculating three-directional ball spinning force in accordance with the theory of space analytic geometry. The contact boundary equation of the ball and tube is obtained. By projection, the two-dimensional curve in each coordinate plane is acquired. The projected area of the contact zone in the coordinate plane is calculated through the curve integral. It is assumed that the average pressure of the forming region is nearly equal to that when the steel ball is pressed into the tube. Hence, the unit pressure of the deformation zone is obtained. Then, the spinning component force and total spinning force are calculated. Using a Tu1 thin-walled tube of oxygen-free copper as experimental object, a ball spinning experiment is conducted, the axial spinning components force are tested and the ball spinning force calculation model is verified. Based on deformation rate, backward sliding accumulation and extension and frictional heating, the factors influencing calculation error are analysed at the end of this paper.
Estimating under-five mortality in space and time in a developing world context
Authors: Wakefield Jon , Fuglstad Geir-Arne , Riebler Andrea , Godwin Jessica , Wilson Katie , Clark Samuel J
Published: April 2018

Accurate estimates of the under-five mortality rate in a developing world context are a key barometer of the health of a nation. This paper describes a new model to analyze survey data on mortality in this context. We are interested in both spatial and temporal description, that is wishing to estimate under-five mortality rate across regions and years and to investigate the association between the under-five mortality rate and spatially varying covariate surfaces. We illustrate the methodology by producing yearly estimates for subnational areas in Kenya over the period 1980–2014 using data from the Demographic and Health Surveys, which use stratified cluster sampling. We use a binomial likelihood with fixed effects for the urban/rural strata and random effects for the clustering to account for the complex survey design. Smoothing is carried out using Bayesian hierarchical models with continuous spatial and temporally discrete components. A key component of the model is an offset to adjust for bias due to the effects of HIV epidemics. Substantively, there has been a sharp decline in Kenya in the under-five mortality rate in the period 1980–2014, but large variability in estimated subnational rates remains. A priority for future research is understanding this variability. In exploratory work, we examine whether a variety of spatial covariate surfaces can explain the variability in under-five mortality rate. Temperature, precipitation, a measure of malaria infection prevalence, and a measure of nearness to cities were candidates for inclusion in the covariate model, but the interplay between space, time, and covariates is complex.
Desistance and Treatment Seeking Among Women With Substance Use Disorders
Authors: Rhodes Blythe E. , Gottfredson Nisha C. , Hill Lauren M.
Published: April 2018

Addiction rates are rising faster among women than men. However, women with substance use disorders are less likely to enter treatment than males. This study seeks to understand how turning-point events and other maturational processes affect “life course persistent” women’s motivations for seeking treatment for their disorder. We conducted semi-structured in-depth interviews with 30 women who were receiving treatment for addiction using thematic analysis. Recurring themes were as follows: experiences of rock-bottom events prior to entering treatment, feeling “sick and tired” in regard to both their physical and mental health, and shifting identities or perceptions of themselves. We discuss the importance of motivating shifts in identity to prevent women from entering treatment as a result of more traumatic mechanisms as well as the possibility of intercepting women with substance dependence and chronic health conditions in primary care or hospital settings with the aim of encouraging treatment.
An Unusual Case of an Odontogenic Keratocyst Associated With an Ungrafted Alveolar Cleft: A Case Report and Review of the Literature
Authors: Radia Sapna , Cash Alexander C. , Moar Kanwalraj
Published: April 2018

We describe an unusual case of an odontogenic keratocyst (OKC) associated with an ungrafted left-sided alveolar cleft in a 10-year-old male patient. There is no previous report in the literature of OKC or other dental cysts associated with an alveolar cleft. We discuss the management of the OKC prior to secondary bone grafting and present this case to highlight the difficulty in the management of OKC concurrent with grafting of the alveolar cleft site, the proximity of unerupted permanent teeth, and possible treatment modalities.
All That Glitters Is Not Gold
Authors: Mende Martin , Scott Maura L. , Bolton Lisa E.
Published: April 2018

A service provider’s conspicuous consumption can undermine customer attitudes and behavioral intentions toward the provider—a so-called penalty effect of conspicuous consumption. Four studies investigate customer and contextual factors that moderate this penalty effect. The results show that customers low in materialism penalize service providers who consume conspicuously (e.g., decreased patronage intentions). In addition, as another facet of the penalty effect, a service provider’s conspicuous consumption undermines customer cost-benefit assessments (decreased perceived value and price fairness), which function as mediating variables. However, service providers can use “service warmth” as a protective strategy to attenuate the penalty effect. Notably, materialistic customers do not react more favorably to service providers who engage in conspicuous consumption (in contrast with their established tendency to favor conspicuous goods). Taken together, the results provide a deeper and theoretically nuanced understanding of when and how customers respond negatively to conspicuous service providers, with meaningful implications for the management of services. For example, when service firms design their aesthetic labor strategy, they should consider their customers’ levels of materialism accordingly. In addition, service firms need to educate their frontline employees about the potential downsides of displaying conspicuous consumption cues.
Approaches to Studying Masculinity: A Nonlinear Perspective of Theoretical Paradigms
Authors: Borkowska Katarzyna
Published: April 2018

The aim of this article is to argue that there is a need to locate theoretical paradigms on masculinity within a nonlinear perspective, and this has implications for the conceptualization of the research agenda. Over the last forty years, discussions and research on masculinity have been arranged in time-related stages where each stage is marked by a change in theoretical underpinnings. These conceptual shifts uphold a distinction between “old” and “new” paradigms, where in consequence, the former or the latter (depending on personal beliefs) becomes devalued to some degree. This article suggests that in the context of masculinity studies, one cannot impede or deny the usefulness and value of the previous theoretical paradigms. Similarly, new paradigms should not be seen as less significant. The approach based on “nonlinearity of theoretical paradigms” acknowledges the coexistence of paradigms, which are seen as equally relevant to contemporary contexts. Moreover, this discussion on nonlinearity implies that research on masculinity, in its search for comprehensiveness, could apply a concept of theoretical paradigm as a modus operandi for each undertaken study.
An Efficient System for Gene Perturbation in Embryonic Hippocampal Progenitors Using Ex Vivo Electroporation Followed by In Vitro Dissociated Cell Culture
Authors: Muralidharan Bhavana , D’Souza Leora , Tole Shubha
Published: April 2018

We established an efficient cell culture assay that permits combinatorial genetic perturbations in hippocampal progenitors to examine cell-autonomous mechanisms of fate specification. The procedure begins with ex vivo electroporation of isolated, intact embryonic brains, in a manner similar to in utero electroporation but with greatly improved access and targeting. The electroporated region is then dissected and transiently maintained in organotypic explant culture, followed by dissociation and plating of cells on coverslips for in vitro culture. This assay recapitulates data obtained in vivo with respect to the neuron-glia cell fate switch and can be effectively used to test intrinsic or extrinsic factors that regulate this process. The advantages of this ex vivo procedure over in utero electroporation include the fact that distinct combinations of perturbative reagents can be introduced in different embryos from a single litter, and issues related to embryonic lethality of transgenic animals can be circumvented.
Tastes and practices in three Australian cultural fields: television, music and sport
Authors: Rowe David , Bennett Tony
Published: April 2018

This article introduces the Themed Section of Media International Australia, ‘Tastes and practices in three Australian cultural fields: television, music and sport’, which presents selected findings of the 2014-2015 survey of Australian cultural practices conducted as part of the Australian Research Council project Australian Cultural Fields: National and Transnational Dynamics (DP140101970). It briefly discusses the social organisation of the production of consumption of Australia in the period between the national cultural policies Creative Nation (1994) and Creative Australia (2013). The Introduction then outlines the methodology underlying the Australian Cultural Fields survey that, in building on the approach of French sociologist Pierre Bourdieu, was developed to assess how far entrenched cultural hierarchies and inequalities have been displaced by broadened patterns of access to arts and culture. Of particular concern is the role of traditional and new forms of cultural capital in differentiating patterns of cultural consumption and participation across relations of class, gender and ethnicity, which the distinctive survey design and administration seek to capture in the Australian context. Bringing together the methods of Multiple Correspondence Analysis (MCA) and Cluster Analysis, each article highlights specific aspects of the relations between cultural tastes, practices, and social positions in contemporary Australia via an engagement with contemporary debates in cultural capital theory. The contributions on television (by Tony Bennett, Modesto Gayo, and David Rowe), music (Ben Dibley and Modesto Gayo) and sport (Modesto Gayo and David Rowe) address the dynamics of these Australian cultural fields, while also indicating the significance of their research findings for studies of other nationally-constituted cultural fields, as well as the contested play of cultural capital within nations and in the transnational/global sphere.
A history of anticipating the future: an analysis of the AN Smith lectures, Andrew Olle Lectures and media commentary
Authors: Fuller Glen , Barnes Renee
Published: April 2018

There are multiple narratives of technological and organisational change for making sense of the news media industry since the turn of the century. In Australia, the Andrew Olle and AN Smith lectures have served as key sites whereby leading members of the journalistic field have articulated narratives of change. Drawing on Bourdieu’s concept of ‘field’ and using Foucault’s notion of ‘commentary’ as a method, we begin by analysing all Andrew Olle and AN Smith lectures from 1997 to 2015 and selected those that substantially discuss journalism and the media industry more broadly. Our analysis develops an account of the narratives of change to better understand the different negotiations and translations of the journalistic field. We found three key narratives: (1) commercial performance and concerns over the decline of ‘quality journalism’, (2) the role of technology in surviving industrial change and (3) fundamental change to journalistic practice.
A method to eliminate unsprung adverse effect of in-wheel motor-driven vehicles
Authors: Nie Shida , Zhuang Ye , Chen Fan , Wang Yong , Liu Shu
Published: April 2018

In-wheel motor-driven vehicles are the development trend for future vehicles due to its high energy efficiency and low emission as well as its flexibility to achieve independent steering, driving, etc. However, the weighted wheel of in-wheel electric vehicles involves more unexpected unsprung vibrations, which imposes adverse effect on vehicle ride comfort. In addition, there exists an invariant point around the unsprung resonance frequency in both controlled and uncontrolled suspensions, which greatly limits the elimination of unsprung adverse effect of in-wheel electric vehicles. In this paper, a combined structure is proposed to eliminate the unsprung adverse effect. The structure is composed of the vehicle suspension and a tuned mass damper, which are both controlled by a sliding mode controller, aiming at eliminating the unsprung adverse effect as well as improving ride comfort across the whole frequency spectrum. The tunes mass damper is used to get rid of the constraint of the invariant point. The simulation and hardware-in-the-loop results show that the root mean square of the sprung mass acceleration and tire deflection is reduced by 31.2% and 2.2% respectively, which indicates that the proposed method is effective and ride comfort is greatly improved.
A Posteriori Segmentation of Personal Profiles of Online Video Games’ Players
Authors: Ramírez-Correa Patricio E. , Rondán-Cataluña F. Javier , Arenas-Gaitán Jorge
Published: April 2018

There are diverse segmentations of online players in the literature. Most of them are proposed a priori, and there are no segmentations based on the acceptance of technology and the personal values of the players. The foremost purpose of this study is to obtain a posteriori segmentation of online video games’ players, founded on unified theory of acceptance and use of technology model, and to describe the subsequent segments consistent with the personal values of Schwartz. The measurement model and the structural model were analyzed with partial least squares (PLS). Subsequently, the PLS-prediction-oriented segmentation technique has been devoted to inspecting unobserved heterogeneity and to find players’ segments. Four segments are obtained from the statistical analysis, and data analysis shown that in each of the segments, the explained variance of both use and behavioral intention (which are the endogenous variables of the model) is significantly improved by comparing the results of the global sample.
Four-Strand Versus 2-Strand Suture-Button Constructs in First Carpometacarpal Arthroplasty: A Biomechanical Study
Authors: Grasu Beatrice L. , Trontis Andrew J. , Parks Brent G. , Wittstadt Raymond A.
Published: April 2018

Background: Suture-button fixation is an alternative to no fixation, first metacarpal distraction techniques, or Kirschner wire fixation after trapeziectomy in treatment of first carpometacarpal (CMC) arthritis. A 4-strand suture-button construct requires a 2.7-mm tunnel, whereas a 2-strand construct requires a 1.1-mm tunnel, potentially decreasing the risk of metacarpal fracture. We compared stability and failure criteria of 4-strand versus 2-strand construct in a biomechanical model of first CMC joint arthroplasty. Methods: Ten fresh-frozen matched pairs of human cadaveric hands were randomized to receive a 4-strand or 2-strand suture-button device. Trapeziectomy and fluoroscopic measurement of the fixed posttrapeziectomy space was performed before and after cycling 1000 times at 0.2 Hz in a custom loading device. The constructs were loaded to failure and failure mechanism was noted. Results: There was no significant difference between the groups in unfixed posttrapeziectomy, fixed precyclic loading, or postcyclic loading height. No difference in pinch pressure was found in any group. No difference in load to failure was observed. The 4-strand device failed through the first ray in 8 of 11 specimens, and the suture of the 2-strand device failed in 5 of 9 specimens. Conclusions: The 4-strand and 2-strand suture-button constructs provide comparable biomechanical stability for first CMC arthroplasty. If construct stability is similar between these procedures, the smaller tunnel used with the 2-strand construct may offer an advantage.
Research on energy conversion characteristic of pump as turbine
Authors: Miao Senchun , Yang Junhu , Shi Fengxia , Wang Xiaohui , Shi Guangtai
Published: April 2018

Pump as turbine is a device for energy conversion. To master the characteristics of energy transformation, especially within impeller, plays important roles for further optimum design of pump as turbine. In order to analyze the energy-changing features in detail using computational fluid dynamics, the impeller is divided into six regions by the radius. Under different operating conditions, the variations of power in the different radial cross-section of the impeller, the input net energy in different regions of the impeller, and the energy from the fluid to the impeller were demonstrated. The results show that the pressure energy of fluid is primary for impeller work, instead of the kinetic energy; the front and middle regions of the impeller (about the area of (0.6–1.0) D2) are important parts for energy conversion; in the rear area of the impeller, it acquires little energy from fluid relatively, what’s more, the fluid not only does not work to impeller, but also consumes the impeller mechanical energy under the large flow conditions. So this research may point out the direction for optimization design of the impeller blade.