bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth, expectations and tariffs
Authors: Honkapohja Seppo , Turunen‐Red Arja H. , Woodland Alan D.
Published: December 2016

We present a growth model of international trade in which expectations about profitability and growth influence innovation and investment. Adaptive learning dynamics determine transition paths for countries with differing structural parameters. Countries limiting trade by tariffs on imports of capital goods can experience gains in growth and perceived utility for a finite time, whereas the rest of the world is adversely affected. Asymmetric gains persist longer when structural advantages of the country applying tariffs are larger. Substantial differences in levels of innovation, output and utility can appear within our asymmetric country setting.
Cross‐border mergers and acquisitions in services: The role of policy and industrial structure
Authors: Barattieri Alessandro , Borchert Ingo , Mattoo Aaditya
Published: December 2016

This paper explores the role of policy and economic structure in determining international mergers and acquisitions (M&A) in services sectors. The analysis is based on bilateral sectoral M&A flow data and detailed information on policy barriers from a new database. Restrictive investment policies are found to reduce the probability of M&A inflows, controlling for bilateral frictions such as geography. This negative effect, however, is mitigated in countries with relatively large shares of manufacturing and (to a lesser extent) services in GDP. The same result holds for the number of M&A deals concluded. Findings are robust to accounting for the potential endogeneity of policy restrictiveness. The evidence suggests that the impact of policy is state‐dependent and related to the composition of GDP in the target economy.
The Clean Development Mechanism in a world carbon market
Authors: Bréchet Thierry , Ménière Yann , Picard Pierre M.
Published: December 2016

This paper discusses the role of the Clean Development Mechanism (CDM) in the market for carbon quotas and countries' commitments to reduce their carbon emission levels. We show that the CDM contributes to an efficient funding of clean technology investments in least developed countries. However, the CDM is not neutral on the global level of carbon emissions as it entices countries to raise their emission caps. The CDM may also make inappropriate the inclusion of any country that takes no emission abatement commitment. It can even make inefficient a country's decision to commit to an emission target. The implications of the presence of non‐additional projects are also analyzed.
Implementing partial tax harmonization in an asymmetric tax competition game with repeated interaction
Authors: Itaya Jun‐ichi , Okamura Makoto , Yamaguchi Chikara
Published: December 2016

This paper investigates the conditions under which partial harmonization for capital taxation is sustained in a repeated interactions model of tax competition when there are three countries with heterogenous capital endowments. We show that regardless of the structure of the coalition (i.e., full or partial tax coordination), whether partial tax harmonization is sustainable or not crucially depends on the extent to which the capital endowment of the medium‐sized country is similar to that of the large or small country. The most noteworthy finding is that the closer the capital endowment of the median country is to the average one, the less likely the tax harmonization including the median country is to prevail and the more likely the partial tax harmonization excluding the median country is to prevail. We also show that partial tax harmonization makes the member countries of the tax union better off and non‐member countries worse off, which stands in sharpe contrast with previous studies, such as Konrad and Schjelderup (1999) and Bucovetsky (2009).
Product sophistication and spillovers from foreign direct investment
Authors: Eck Katharina , Huber Stephan
Published: December 2016

Foreign direct investment (FDI) in developing countries is often associated with higher economic growth due to knowledge and technology spillovers to local firms. One way that FDI speeds up growth is by facilitating the manufacturing of more sophisticated products by local firms. So far, there is a lack of firm‐level evidence how the presence of multinational firms affects the product sophistication of firms in a developing country. The aim of this paper is to fill this gap. We compile an extensive firm–product‐level data set of Indian manufacturing firms, which we complement with information on product sophistication and spillovers from FDI. We then explore different channels through which spillovers from multinationals to local Indian firms foster the manufacturing of sophisticated products. We find evidence that spillovers through supplier linkages strongly increase the manufacturing of sophisticated products in India.
Changing income inequality: A distributional paradigm for Canada
Authors: Beach Charles M.
Published: December 2016

This paper examines the major changes in income inequality in Canada since the 1970s and collects them as a distributional paradigm for Canada. It focuses on labour market changes in terms of shares of workers and earnings shares for lower earners, middle‐class workers and higher earners in a flexible general framework. Polarization of full‐time workers, loss of middle‐class earnings share and increase in a higher earnings gap are highlighted. Changing returns to human capital, role of demographics and cohort effects and declining labour share are examined. The paper also reviews evidence of changing economic mobility and estimating the role of inequality of opportunity.
Targeting MUC1 and JNK by RNA interference and inhibitor inhibit the development of hepatocellular carcinoma
Authors: Wang Juan , Ni Wei‐hua , Hu Ke‐bang , Zhai Xiao‐yu , Xie Fei , Jie Jing , Zhang Nan‐nan , Jiang Li‐na , Yuan Hong‐yan , Tai Gui‐xiang
Published: December 2016

Mucin 1 (MUC1), as an oncogene, is overexpressed in hepatocellular carcinoma (HCC) cells and promotes the progression and tumorigenesis of HCC through JNK/TGF‐β signaling pathway. In the present study, RNA interference (RNAi) and JNK inhibitor SP600125, which target MUC1 and/or JNK, were used to treat HCC cells in vitro, and the results showed that both silencing the expression of MUC1 and blocking the activity of JNK inhibited the proliferation of HCC cells. In addition, MUC1‐stable‐knockdown and SP600125 significantly inhibited the growth of tumors in the subcutaneous transplant tumor models that established in BALB/c nude mice rather than MUC1 or JNK siRNAs transiently transfection. Furthermore, the results from immunohistochemical staining assays showed that the inhibitory effects of MUC1 gene silencing and SP600125 on the proliferation of HCC cells in vivo were through the JNK/TGF‐β signaling pathway. These results indicate that MUC1 and JNK are attractive targets for HCC therapy and may provide new therapeutic strategies for the treatment of HCC.
MET4 expression predicts poor prognosis of gastric cancers with Helicobacter pylori infection
Authors: Sakamoto Naoko , Tsujimoto Hironori , Takahata Risa , Cao Brian , Zhao Ping , Ito Nozomi , Shimazaki Hideyuki , Ichikura Takashi , Hase Kazuo , Vande Woude George F. , Shinomiya Nariyoshi
Published: December 2016

The role of HGF/SF‐MET signaling is important in cancer progression, but its relation with Helicobacter pylori‐positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti‐HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan–Meier method and compared with log‐rank. Cox proportional hazards models were fit to determine the independent association of MET‐staining status with outcome. The effect of live H. pylori bacteria on cell signaling and biological behaviors was evaluated using gastric cancer cell lines. MET4‐positive gastric cancers showed poorer prognosis than MET4‐negative cases (overall survival, P = 0.02; relapse‐free survival, P = 0.06). Positive staining for MET4 was also a statistically significant factor to predict poor prognosis in H. pylori‐positive cases (overall survival, P < 0.01; relapse‐free survival, P = 0.01) but not in H. pylori‐negative cases. Gastric cancers positively stained with both HGF/SF and MET4 showed a tendency of the worst prognosis. Stimulation of MET‐positive gastric cancer cells with live H. pylori bacteria directly upregulated MET phosphorylation and activated MET downstream signals such as p44/42MAPK and Akt, conferring cell proliferation and anti‐apoptotic activity. In conclusion, positive staining for MET4 was useful for predicting poor prognosis of gastric cancers with H. pylori infection. Helicobacter pylori stimulated MET‐positive gastric cancers and activated downstream signaling, thereby promoting cancer proliferation and anti‐apoptotic activity. These results support the importance of H. pylori elimination from gastric epithelial surface in clinical therapy.
Hypoxia promotes the phenotypic change of aldehyde dehydrogenase activity of breast cancer stem cells
Authors: Shiraishi Akira , Tachi Kana , Essid Nesrine , Tsuboi Ikki , Nagano Masumi , Kato Toshiki , Yamashita Toshiharu , Bando Hiroko , Hara Hisato , Ohneda Osamu
Published: December 2016

Stable breast cancer cell (BCC) lines are valuable tools for the identification of breast cancer stem cell (BCSC) phenotypes that develop in response to several stimuli as well as for studying the basic mechanisms associated with the initiation and maintenance of BCSCs. However, the characteristics of individual, BCC‐derived BCSCs varies and these cells show distinct phenotypes depending on the different BCSC markers used for their isolation. Aldehyde dehydrogenase (ALDH) activity is just such a recognized biomarker of BCSCs with a CD44+/CD24− phenotype. We isolated BCSCs with high ALDH activity (CD44+/CD24−/Aldefluorpos) from a primary culture of human breast cancer tissue and observed that the cells had stem cell properties compared to BCSCs with no ALDH activity (CD44+/CD24−/Aldefluorneg). Moreover, we found Aldefluorpos BCSCs had a greater hypoxic response and subsequent induction of HIF‐1α expression compared to the Aldefluorneg BCSCs. We also found that knocking down HIF‐1α, but not HIF‐2α, in Aldefluorpos BCSCs led to a significant reduction of the stem cell properties through a decrease in the mRNA levels of genes associated with the epithelial‐mesenchymal transition. Indeed, HIF‐1α overexpression in Aldefluorneg BCSCs led to Slug and Snail mRNA increase and the associated repression of E‐cadherin and increase in Vimentin. Of note, prolonged hypoxic stimulation promoted the phenotypic changes of Aldefluorneg BCSCs including ALDH activity, tumorigenesis and metastasis, suggesting that hypoxia in the tumor environment may influence BCSC fate and breast cancer clinical outcomes.
Longitudinal monitoring of gene expression in ultra-low-volume blood samples self-collected at home
Authors: Speake C , Whalen E , Gersuk V H , Chaussabel D , Odegard J M , Greenbaum C J
Published: December 2016

Blood transcriptional profiles could serve as biomarkers of clinical changes in subjects at-risk for or diagnosed with diabetes. However, transcriptional variation over time is poorly understood due to the impracticality of frequent longitudinal phlebotomy in large patient cohorts. We have developed a novel transcriptome assessment method that could be applied to fingerstick blood samples self-collected by study volunteers. Fifteen μL of blood from a fingerstick yielded sufficient RNA to analyse > 176 transcripts by high-throughput quantitative polymerase chain reaction (PCR). We enrolled 13 subjects with type 1 diabetes and 14 controls to perform weekly collections at home for a period of 6 months. Subjects returned an average of 24 of 26 total weekly samples, and transcript data were obtained successfully for > 99% of samples returned. A high degree of correlation between fingerstick data and data from a standard 3 mL venipuncture sample was observed. Increases in interferon-stimulated gene expression were associated with self-reported respiratory infections, indicating that real-world transcriptional changes can be detected using this assay. In summary, we show that longitudinal monitoring of gene expression is feasible using ultra-low-volume blood samples self-collected by study participants at home, and can be used to monitor changes in gene expression frequently over extended periods.
Pathogens and antibiotic sensitivities in endophthalmitis
Authors: Slean Geraldine R , Shorstein Neal H , Liu Liyan , Paschal John F , Winthrop Kevin L , Herrinton Lisa J
Published: December 2016

Background

Antibiotic prophylaxis in cataract surgery is intended to minimize endophthalmitis. We describe pathogenic organisms, antibiotic sensitivities and antibiotic prophylaxis in culture‐proven endophthalmitis cases.

Design

Retrospective consecutive case series and community‐based setting were used.

Participants

Two hundred fifteen cases of endophthalmitis after cataract surgery performed during 2007–2012 in Kaiser Permanente, California.

Methods and Main Outcome Measures

Descriptive analysis of isolated organisms and antibiotic sensitivities in relation to antibiotic prophylaxis in culture‐proven endophthalmitis cases.

Results

The majority of culture‐confirmed organisms (n = 83) were Gram positive (96%), most notably coagulase‐negative Staphylococci (n = 34, 52%), of which all that underwent testing were sensitive to vancomycin (n = 32). Among 19 cases that had received only topical antibiotic prophylaxis, seven (37%) were resistant to the antibiotic given: 50% of cases (5 of 10 isolates) that had received ofloxacin were resistant to this antibiotic, 40% (2 of 5 isolates) that had received gatifloxacin were resistant. In contrast, 100% of cases (n = 4) that had received aminoglycosides were susceptible. Few culture‐confirmed cases occurred in patients who received intracameral antibiotic (n = 4).

Conclusions

In cases where fluoroquinolones were administered as antibiotic prophylaxis, isolates demonstrated a degree of bacterial resistance. The majority of endophthalmitis cases isolated occured following topical antibiotic prophylaxis only and were attributed to Gram‐positive organisms, while few occurred in association with intracameral antibiotic.
Mitochondrial phylogenomics illuminates the evolutionary history of Neuropterida
Authors: Wang Yuyu , Liu Xingyue , Garzón‐Orduña Ivonne J. , Winterton Shaun L. , Yan Yan , Aspöck Ulrike , Aspöck Horst , Yang Ding
Published: December 2016

Neuroptera (lacewings) and allied orders Megaloptera (dobsonflies, alderflies) and Raphidioptera (snakeflies) are predatory insects and together make up the clade Neuropterida. The higher‐level relationships within Neuropterida have historically been widely disputed with multiple competing hypotheses. Moreover, the evolution of important biological innovations among various Neuropterida families, such as the origin, timing and direction of transitions between aquatic and terrestrial habitats of larvae, remains poorly understood. To investigate the origin and diversification of lacewings and their allies, we undertook phylogenetic analyses of mitochondrial genomes of all families of Neuropterida using Bayesian inference, maximum likelihood and maximum parsimony methods. We present a robust, fully resolved phylogeny and divergence time estimation for Neuropterida with strong statistical support for almost all nodes. Mitochondrial sequence data are typified by significant compositional heterogeneity across lineages, and parsimony and models assuming homogeneous rates did not recover Neuroptera as monophyletic. Only a model accounting for compositional heterogeneity (i.e. CAT‐GTR) recovered all orders of Neuropterida as monophyletic. Significant findings of the mitogenomic phylogeny include recovering Raphidioptera as sister to Megaloptera plus Neuroptera. The sister family of all other lacewings are the dusty‐wings (Coniopterygidae), rather than Nevrorthidae. Nevrorthidae are instead returned to their traditional position as the sister group of the spongilla‐flies (Sisyridae) and closely related to Osmylidae. Our divergence time analysis indicates that the Mesozoic was indeed a ‘golden age’ for lacewings, with most families of Neuropterida diverging during the Triassic and Jurassic and all extant families present by the Early Cretaceous. Based on ancestral character state reconstructions of larval habitat we evaluate competing hypotheses regarding the life style of early neuropteridan larvae as either aquatic or terrestrial.
Intra‐surgical vs. radiographic bone level assessments in measuring peri‐implant bone loss
Authors: Serino Giovanni , Sato Hirohisa , Holmes Patrick , Turri Alberto
Published: December 2016

Objective

To evaluate the accuracy between the intra‐surgical and the peri‐apical radiographic measurements of bone loss at implant with peri‐implantitis.

Materials and methods

A total of 46 Brånemark implants in 24 patients with diagnosis of peri‐implantitis were included in the study. The amount of peri‐implant bone loss occurred at those implants was measured during peri‐implant surgery and compared to the radiographic bone loss measured by three independent examiners.

Results

The mean bone loss measured on radiographs underestimated the intra‐surgical bone loss at the correspondent sites (0.7 mm at the mesial and 0.6 mm at the distal sites); this underestimation was found to be a consistent finding in all the three examiners. Only 21% of the radiographic measurements corresponded to the clinical bone loss assessments, while an over‐ and underestimation within a range of ± 1–2 mm was recorded in 57% of the cases. There was a moderate positive linear correlation between the radiographic measurements and the clinical bone loss for mesial and distal sites (r = range 0.58–0.65). The variability between the three examiners in the radiographic measurements was frequently on the range of ± 1–2 mm.

Conclusion

The radiographic measurements of bone loss at implant affected by peri‐implantitis often underestimated the clinical bone loss occurred at the implants. A difference of about ± 1–2 mm in the estimation of radiographic bone loss could be merely assigned as inter‐examiner different assessments.
The prominence of smoking‐related mortality among individuals with alcohol‐ or drug‐use disorders
Authors: Callaghan Russell C. , Gatley Jodi M. , Sykes Jenna , Taylor Lawren
Published: December 2016

Introduction and Aims

Even though individuals with substance‐use disorders have a high prevalence of tobacco smoking, surprisingly little is known about smoking‐related mortality in these populations. The current retrospective cohort study aims to address this gap.

Design and Methods

The study sample included cohorts of individuals hospitalised in California between 1990 and 2005 with alcohol‐ (n = 509 422), cocaine‐ (n = 35 276), opioid‐ (n = 53 172), marijuana‐ (n = 15 995) or methamphetamine‐use (n = 36 717) disorders. Death records were linked to inpatient data. Age‐, race‐ and sex‐adjusted standardised mortality ratios (SMR) were generated for 19 smoking‐related causes of death.

Results

Smoking‐related conditions comprised 49% (79 188/163 191) of total deaths in the alcohol, 40% (1412/3570) in the cocaine, 39% (4285/11 091) in the opioid, 42% (554/1332) in the methamphetamine and 36% (1122/3095) in the marijuana cohorts. The SMRs for all smoking‐linked diseases were: alcohol, 3.57 (95% confidence interval [CI] = 3.55 to 3.58); cocaine, 2.40 (95% CI = 2.39 to 2.41); opioid, 4.26 (95% CI = 4.24 to 4.27); marijuana, 3.73 (95% CI = 3.71 to 3.74); and methamphetamine, 2.58 (95% CI = 2.57 to 2.59). The SMRs for almost all of the 19 cause‐specific smoking‐related outcomes were elevated across cohorts.

Discussion and Conclusions

Given the current findings, addressing tobacco smoking among persons with substance‐use disorders should be a critical concern, especially given the heavy smoking‐related mortality burden and the currently limited attention devoted to smoking in these populations. [Callaghan RC, Gatley JM, Sykes J, Taylor L. The prominence of smoking‐related mortality among individuals with alcohol‐ or drug‐use disorders. Drug Alcohol Rev 2018;37:97–105]
The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis
Authors: Hum Justine , Shatzel Joseph J. , Jou Janice H. , Deloughery Thomas G.
Published: December 2016

Introduction

The coagulopathy of cirrhosis is complex, placing patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have equivalent or superior efficacy and safety as compared to vitamin K antagonists (VKAs); however, their efficacy and safety in liver cirrhosis has not been studied. To better define this, we evaluated outcomes of patients with cirrhosis prescribed DOACs compared to other anticoagulants at our center.

Methods

Retrospective cohort study of patients with cirrhosis prescribed therapeutic anticoagulation over a 3‐year period for thrombosis or prevention of stroke in patients with atrial fibrillation. The primary outcomes of interest were bleeding events and recurrent thrombosis or stroke.

Results

During the study period, 27 patients with cirrhosis were prescribed a DOAC and 18 were prescribed VKA or low molecular weight heparin (LMWH). Both groups had similar total bleeding events (8 DOAC vs 10 other, P=.12). There were significantly less major bleeding episodes in the DOAC group (1 [4%] vs 5 [28%], P=.03). Recurrent thrombosis occurred in one patient receiving a DOAC (4%) and one patient (6%) receiving other anticoagulation (P=1.0).

Conclusions

Direct oral anticoagulant use in patients with cirrhosis may be as safe as traditional anticoagulants. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or thrombosis.
Predictive factors for anemia response to erythropoiesis‐stimulating agents in myelofibrosis
Authors: Hernández‐Boluda Juan‐Carlos , Correa Juan‐Gonzalo , García‐Delgado Regina , Martínez‐López Joaquín , Alvarez‐Larrán Alberto , Fox María‐Laura , García‐Gutiérrez Valentín , Pérez‐Encinas Manuel , Ferrer‐Marín Francisca , Mata‐Vázquez María‐Isabel , Raya José‐María , Estrada Natalia , García Silvia , Kerguelen Ana , Durán María‐Antonia , Albors Manuel , Cervantes Francisco
Published: December 2016

Objective

Erythropoiesis‐stimulating agents (ESAs) are commonly used to treat the anemia of myelofibrosis (MF), but information on the predictors of response is limited.

Methods

Results of ESA therapy were analyzed in 163 MF patients with severe anemia, most of whom had inadequate erythropoietin (EPO) levels (<125 U/L) at treatment start.

Results

According to the revised criteria of the International Working Group for Myelofibrosis Treatment and Research, anemia response was achieved in 86 patients (53%). Median response duration was 19.3 months. In multivariate analysis, baseline factors associated with a higher response rate were female sex (P=.007), leukocyte count ≥10×109/L (P=.033), and serum ferritin <200 ng/mL (P=.002). Patients with 2 or 3 of the above features had a significantly higher response rate than the remainder (73% vs 28%, respectively; P<.001). Over the 373 patient‐years of follow‐up on ESA treatment, nine patients developed thrombotic complications (six arterial, three venous), accounting for 2.41 events per 100 patient‐years. Survival time from ESA start was longer in anemia responders than in non‐responders (P=.011).

Conclusion

Besides the already established predictive value of EPO levels, these data can help to identify which MF patients are more likely to benefit from ESA treatment.
Verbal memory after temporal lobe epilepsy surgery in children: Do only mesial structures matter?
Authors: Law Nicole , Benifla Mony , Rutka James , Smith Mary Lou
Published: December 2016

Objective

Previous findings have been mixed regarding verbal memory outcome after left temporal lobectomy in children, and there are few studies comparing verbal memory change after lateral versus mesial temporal lobe resections. We compared verbal memory outcome associated with sparing or including the mesial structures in children who underwent left or right temporal lobe resection. We also investigated predictors of postsurgical verbal memory change.

Methods

We retrospectively assessed verbal memory change approximately 1 year after unilateral temporal lobe epilepsy surgery using a list learning task. Participants included 23 children who underwent temporal lobe surgery with sparing of the mesial structures (13 left), and 40 children who had a temporal lobectomy that included resection of mesial structures (22 left).

Results

Children who underwent resection from the left lateral and mesial temporal lobe were the only group to show decline in verbal memory. Furthermore, when we considered language representation in the left temporal resection group, patients with left language representation and spared mesial structures showed essentially no change in verbal memory from preoperative to follow‐up, whereas those with left language representation and excised mesial structures showed a decline. Postoperative seizure status had no effect on verbal memory change in children after left temporal lobe surgery. Finally, we found that patients with intact preoperative verbal memory experienced a significant decline compared to those with below average preoperative verbal memory.

Significance

Our findings provide evidence of significant risk factors for verbal memory decline in children, specific to left mesial temporal lobe epilepsy. Children who undergo left temporal lobe surgery that includes mesial structures may be most vulnerable for verbal memory decline, especially when language representation is localized to the left hemisphere and when preoperative verbal memory is intact.
TRPC3 channels play a critical role in the theta component of pilocarpine‐induced status epilepticus in mice
Authors: Phelan Kevin D. , Shwe U Thaung , Cozart Michael A. , Wu Hong , Mock Matthew M. , Abramowitz Joel , Birnbaumer Lutz , Zheng Fang
Published: December 2016

Objective

Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell‐specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain‐derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine‐induced status epilepticus (SE).

Methods

The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3‐selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine‐induced seizures were performed.

Results

We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root‐mean‐square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine‐induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine‐induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine‐induced SE and a selective reduction in the theta activity during SE.

Significance

Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine‐induced SE and could be a novel molecular target for new anticonvulsive drugs.
Uptake and efflux kinetics, and intracellular activity of voriconazole against Aspergillus fumigatus in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis
Authors: Wang Taotao , Yang Qianting , Chen Lu , Li Ying , Meng Ti , Wang Yan , Zhang Tao , Lei Jin'e , Xing Jianfeng , Dong Yalin
Published: December 2016

Invasive pulmonary aspergillosis (IPA), most caused by Aspergillus fumigatus, is a serious life‐threatening infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against A. fumigatus in A549 cells. High‐performance liquid chromatography/tandem mass spectrometry and time‐kill method were used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole. Voriconazole exerted a concentration‐dependent toxic effect on A549 cells and could penetrate into cells, reaching plateau concentrations of 1.14 ± 0.64, 3.72 ± 1.38 and 6.36 ± 0.95 ng/mg protein after A549 cells were exposed to voriconazole at extracellular concentrations of 2, 8 and 16 mg/L for 2 h, respectively. The efflux of voriconazole was rapid, with a half‐life of 10.2 min. Voriconazole can decrease the A. fumigatus conidia invade cells, and the number of viable A. fumigatus conidia in cells can be decreased 2.1‐ to 20.6‐fold when A549 cells were cultured in medium containing voriconazole. After 24‐h incubation, 75.6% and 80.5% of intracellular A. fumigatus were killed when extracellular voriconazole concentration was 8 and 16 mg/L, respectively. This study illustrated a new application for the prophylaxis and early treatment of IPA from the cellular pharmacokinetics and pharmacodynamics and emphasized the importance of monitoring concentrations of voriconazole in epithelial lining fluid in immunocompromised patients receiving voriconazole therapy.
Assessing forest vulnerability to climate warming using a process‐based model of tree growth: bad prospects for rear‐edges
Authors: Sánchez‐Salguero Raúl , Camarero Jesus Julio , Gutiérrez Emilia , González Rouco Fidel , Gazol Antonio , Sangüesa‐Barreda Gabriel , Andreu‐Hayles Laia , Linares Juan Carlos , Seftigen Kristina
Published: December 2016

Growth models can be used to assess forest vulnerability to climate warming. If global warming amplifies water deficit in drought‐prone areas, tree populations located at the driest and southernmost distribution limits (rear‐edges) should be particularly threatened. Here, we address these statements by analyzing and projecting growth responses to climate of three major tree species (silver fir,Abies alba; Scots pine,Pinus sylvestris; and mountain pine,Pinus uncinata) in mountainous areas ofNESpain. This region is subjected to Mediterranean continental conditions, it encompasses wide climatic, topographic and environmental gradients, and, more importantly, it includes rear‐edges of the continuous distributions of these tree species. We used tree‐ring width data from a network of 110 forests in combination with the process‐based Vaganov–Shashkin‐Lite growth model and climate–growth analyses to forecast changes in tree growth during the 21st century. Climatic projections were based on four ensemblesCO2emission scenarios. Warm and dry conditions during the growing season constrain silver fir and Scots pine growth, particularly at the species rear‐edge. By contrast, growth of high‐elevation mountain pine forests is enhanced by climate warming. The emission scenario (RCP8.5) corresponding to the most pronounced warming (+1.4 to 4.8 °C) forecasted mean growth reductions of −10.7% and −16.4% in silver fir and Scots pine, respectively, after 2050. This indicates that rising temperatures could amplify drought stress and thus constrain the growth of silver fir and Scots pine rear‐edge populations growing at xeric sites. Contrastingly, mountain pine growth is expected to increase by +12.5% due to a longer and warmer growing season. The projections of growth reduction in silver fir and Scots pine portend dieback and a contraction of their species distribution areas through potential local extinctions of the most vulnerable driest rear‐edge stands. Our modeling approach provides accessible tools to evaluate forest vulnerability to warmer conditions.
In vitro probiotic evaluation of potential antioxidant lactic acid bacteria isolated from idli batter fermented with Piper betle leaves
Authors: Sadishkumar Vishwanathan , Jeevaratnam Kadirvelu
Published: December 2016

Lactic acid bacteria isolated from food sources can be introduced as probiotics because of their health‐promoting and nonpathogenic characteristics. Eight lactic acid bacteria from idli batter fermented with Piper betle leaves were selected to screen the antioxidant potential and biofilm‐forming ability. Five isolates exhibited good antioxidant potential and biofilm formation and showed antagonistic activity against the pathogenic biofilm‐forming Staphylococcus aureus. Further, in vitro probiotic properties of five isolates exhibited excellent acid tolerance, bile tolerance, simulated gastrointestinal juice tolerance, auto‐aggregation and co‐aggregation and hydrophobicity and showed resistance to antibiotics such as ciprofloxacin, nalidixic acid, norfloxacin and colistin. Isolates also showed positive bile salt hydrolase activity, cholesterol assimilation, β‐galactosidase production and mucin binding ability. The isolate KJBB10 exhibited good adhesion and pathogen exclusion percentage with human colon cancer cells (HCT‐15 and HT‐29). Hence, the isolates KJBB10, KJBB56 and KJBC06 can be used as beneficial probiotic starter cultures for the formulation of functional foods.
Effect of thermal processing on phenolic profiles and antioxidant activities in Castanea mollissima
Authors: Liu Fengyuan , Chang Xiaoxiao , Hu Xiaodan , Brennan Charles S. , Guo Xinbo
Published: December 2016

The effect of three domestic thermal processing methods on chestnut fruit was analysed in this study. By evaluating the changes of the contents of free and bound phenolic profiles as well as the antioxidant activity in chestnut fruit, our study indicated that steaming could better preserve and enhance the level of phenolics and flavonoids in chestnut fruit and thus brought to a higher antioxidant activity. Microwaving could increase the phenolic content and the antioxidant activity of chestnut fruits within a short time, while blanching caused a decrease of flavonoid contents. In addition, our research suggested that there was formation of new phenolics in chestnut fruit, which were discovered during thermal processing because of the increases of bound phenolics after processing. Therefore, the potential of chestnut fruits to be developed as a kind of functional food could be highly expected.
Phytochemical composition, cellular antioxidant capacity and antiproliferative activity in mango (Mangifera indica L.) pulp and peel
Authors: Abbasi Arshad Mehmood , Liu Fengyun , Guo Xinbo , Fu Xiong , Li Tong , Liu Rui Hai
Published: December 2016

Cellular antioxidant activity (CAA) and inhibition of hepato‐cellular carcinoma (HepG2) proliferation were evaluated for the first time in the pulp and peel of mango cultivars. Comparatively, peel had high flavonoids and tocopherols content and showed significant antioxidant activity. Among all the studied cultivars, the Xiao Tainong peel was predominant with highest fistein, mangiferin and alpha‐tocopherol content and significant cellular antioxidant activity value 2986 ± 380 μmol QE/100 g FW. The HepG2 cells antiproliferation was maximum in the peel of Da Tainong and pulp of Aozhou with lowest EC50 values, 2.35 ± 0.65 (peel) and 185.4 ± 10.9 (pulp) mg mL−1, in a dose‐dependent manner. Negative associations of flavonoids and tocopherol compounds with CAA and antiproliferative activity in mango confirmed synergistic, additive or antagonistic actions of phytochemicals. The current study suggests that mango peel could be used as a value added ingredient or functional food and may contribute considerably to promote consumer health.
Myeloperoxidase in blood neutrophils during normal and abnormal menstrual cycles in women of reproductive age
Authors: Shibata T. , Sakamoto J. , Osaka Y. , Neyatani N. , Fujita S. , Oka Y. , Takagi H. , Mori H. , Fujita H. , Tanaka Y. , Sasagawa T.
Published: December 2016

Introduction

We previously reported that granulocyte colony‐stimulating factor (G‐CSF) plays a critical role in ovulation, suggesting that neutrophils may maintain ovulation. We assessed myeloperoxidase (MPO), a major and specific enzyme of neutrophils, in women with abnormal and normal menstrual cycles to clarify the relationship between MPO and ovulation.

Methods

We analyzed MPO activity in blood neutrophils of women with abnormal menstrual cycles (indicative of anovulation, n = 12) and age‐ and body mass index‐matched normal menstrual cycles (indicative of ovulation, n = 24) using two parameters as a marker of MPO, Neut X and mean peroxidase index (MPXI).

Results

MPO of women with abnormal menstrual cycles was significantly lower than that of women with normal menstrual cycles [Neut X: 62.6 ± 1.1 (mean ± standard error of the mean) vs. 66.2 ± 0.3, P = 0.009; MPXI: −0.54 ± 1.66 vs. 4.91 ± 0.53, P = 0.008]. Among women with normal menstrual cycles, MPO was highest in the follicular phase (Neut X: 67.0 ± 0.3; P = 0.033).

Conclusion

The difference in MPO between women with abnormal and normal menstrual cycles and the upregulation of MPO before ovulation suggest that neutrophils and MPO are closely related to ovulation.
Japanese Society for Laboratory Hematology flow cytometric reference method of determining the differential leukocyte count: external quality assurance using fresh blood samples
Authors: Kawai Y. , Nagai Y. , Ogawa E. , Kondo H.
Published: December 2016

Introduction

To provide target values for the manufacturers’ survey of the Japanese Society for Laboratory Hematology (JSLH), accurate standard data from healthy volunteers were needed for the five‐part differential leukocyte count. To obtain such data, JSLH required an antibody panel that achieved high specificity (particularly for mononuclear cells) using simple gating procedures. We developed a flow cytometric method for determining the differential leukocyte count (JSLH‐Diff) and validated it by comparison with the flow cytometric differential leukocyte count of the International Council for Standardization in Haematology (ICSH‐Diff) and the manual differential count obtained by microscopy (Manual‐Diff).

Methods

First, the reference laboratory performed an imprecision study of JSLH‐Diff and ICSH‐Diff, as well as performing comparison among JSLH‐Diff, Manual‐Diff, and ICSH‐Diff. Then two reference laboratories and seven participating laboratories performed imprecision and accuracy studies of JSLH‐Diff, Manual‐Diff, and ICSH‐Diff. Simultaneously, six manufacturers’ laboratories provided their own representative values by using automated hematology analyzers.

Results

The precision of both JSLH‐Diff and ICSH‐Diff methods was adequate. Comparison by the reference laboratory showed that all correlation coefficients, slopes and intercepts obtained by the JSLH‐Diff, ICSH‐Diff, and Manual‐Diff methods conformed to the criteria. When the imprecision and accuracy of JSLH‐Diff were assessed at seven laboratories, the CV% for lymphocytes, neutrophils, monocytes, eosinophils, and basophils was 0.5~0.9%, 0.3~0.7%, 1.7~2.6%, 3.0~7.9%, and 3.8~10.4%, respectively. More than 99% of CD45 positive leukocytes were identified as normal leukocytes by JSLH‐Diff.

Conclusions

When JSLH‐Diff method were validated by comparison with Manual‐Diff and ICSH‐Diff, JSLH‐Diff showed good performance as a reference method.
Retroperitoneal liposarcoma excreting insulin‐like growth factor 2 that induced severe hypoglycemia
Authors: Kato Takuma , Sugimoto Mikio , Yamashita Motoki , Miyauchi Yasuyuki , Hirama Hiromi , Tsunemori Hiroyuki , Ueda Nobufumi , Imachi Hitomi , Shibuya Shinsuke , Kushida Yoshio , Kakehi Yoshiyuki
Published: December 2016

Insulin‐like growth factor 2 is overexpressed in various cancers, and is associated with a poor prognosis. Also, it is known that insulin‐like growth factor 2 is an etiology of non‐islet cell tumor hypoglycemia. In this report, we describe a case of unexpected hypoglycemia caused by a dedifferentiated liposarcoma producing insulin‐like growth factor 2. A large mass in the retroperitoneum was detected in a 61‐year‐old man who complained of appetite loss. Despite having no history of diabetes mellitus, hypoglycemia suddenly occurred after admission, but oral glucose therapy was ineffective. After total parenteral nutrition, tumor resection was attempted, but failed as a result of rigid adhesion to the surrounding organs. The patient died of the disease 21 days after surgery. Pathological diagnosis at autopsy revealed dedifferentiated liposarcoma, and immunohistochemical staining showed that the tumor excreted insulin‐like growth factor 2. The possibility of an insulin‐like growth factor 2‐producing tumor should be taken into consideration when we encounter a patient with spontaneous hypoglycemia resistant to glucose substitution therapy.
Missional Discipleship
Authors: Gibson Ezekiel Lesmore
Published: December 2016

Most communities of the world, and particularly in the continent of Africa, are multi‐faith and multicultural. Christianity is a major religion in the continent that has succeeded in persuading adherents of African traditional religions to switch off from their indigenous belief and switch on to Christian belief. Christianity is not the only religious faith in Africa. It has other sibling monotheistic religions and other religious expressions. Christianity, being a mission‐oriented religious faith, has a mandate to bring about transformation as reflected in its sacred text, the Bible. This article will explore how the transformation is stimulated and sustained. Meanwhile, it is necessary to state that African people were religious people even before the advent of Christianity and Islam. As a result, religion plays a critical role in their public engagements. Nevertheless, what may be investigated further would be whether religion, and Christian faith in particular, influences the people to be good citizens/disciples as they engage in the socio‐political and economic life of the society. The article seeks to use the notion of missional discipleship as a compelling stimulus for inclusive transformation in African societies.
Reflecting and Confessing in the Spirit
Authors: Yong Amos
Published: December 2016

The Arusha, Tanzania, 2018 World Mission Conference theme, “Moving in the Spirit: Called to Transforming Discipleship,” can be read from one perspective as acknowledging the continued growth and expansion of pentecostal and charismatic movements across the world Christian stage, especially in the majority world. Such ongoing developments beg the question of whether pentecostal and charismatic renewal has anything to contribute to global mission theology and theologizing in the present time. This essay suggests that the Spirit‐filled and empowered life invites a pneumatological imagination, hermeneutic, and theological method that carves out a via media between a fundamentalistic scripturalism that neglects the ongoing work of the Spirit on the one side, and a subjectivistic experientialism that is untethered to the biblical and theological tradition on the other. Such an approach will be exemplified – not just laid out propositionally (or “scientifically,” in the old tradition of hermeneutics, understood as the science of interpretation) – in light of the Day of Pentecost narrative as recorded in the book of Acts.
What Happens when History Does Not Walk as We Wish?
Authors: McGeoch Graham
Published: December 2016

The modern ecumenical movement calls the churches to pray together and to stay together. Through the World Council of Churches, this call has been supported by theological reflection, most notably on baptism, eucharist and ministry and, more recently, ecclesiology. It has also been nurtured by the missionary movement and its practical calls to common witness and service.

This article sets out the context of the work of a parish church in Edinburgh, UK. It provides context to ecumenical and interfaith relations in the parish and to pastoral work within what is called the pink triangle. It concludes with a reflection on John Zizioulas's local church and considers the implications of an ecclesiology and missiology that reflect the life of the parish: “While cherishing the unity of the Spirit in the one Church, it is also important to honour the ways in which each local congregation is led by the spirit to respond to its own contextual realities.”
Noah's Ark, Mt. Meru, and the God of the Rainbow
Authors: Chang Yoon‐Jae
Published: December 2016

The warning is clear: Unless human beings reach a change of civilization in the ecological sense within the next ten years, we will not have a future—any future. However, a change of civilization does require a change of religious beliefs as well. As Lynn White Jr. asserted many years ago, our present science and technology are so tinctured with orthodox Christian arrogance toward nature that no solution for our ecological and economic crises can be expected from them alone. “Since the roots of our trouble are so largely religious,” as White assures, “the remedy must also be essentially religious.” Still, where do we begin? The author is convinced that any ecological reconstruction of Christian theology and missiology must begin with the Scripture. A solid re‐reading of the Bible will do. This is the reason why the author revisits the well‐known story of Noah's ark to reveal the inconvenient truth almost verbatim – the truth that the Noah's Ark is the story of God's new covenant of life with not only human beings but also with the Earth, represented by the animals from the ark. After scrutinizing the creation stories in Genesis 1 to 9, comparing in particular the two different commandments of God in Genesis 1 and Genesis 2, as well as in Genesis 1 and Genesis 9, the author confirms that a just and sustainable future can only be built upon the biblical God of the rainbow, who shows no favor to human beings, and who makes a new covenant of life with all flesh. What we need is a new vision of Christian beliefs and discipleship that honors God, values the Earth, and emphasizes humility [humus] of humanity [humus], concludes the author.
Fostering a Spirituality That Can Transform Mission?
Authors: Corlett Janet
Published: December 2016

To be moved by the Spirit into transforming discipleship, we need to know how to make ourselves available to God to receive God's gifts. We also need to practise discernment regarding what gives life and what does not. This paper considers themes for the 2018 Mission Conference, including money, love, and prayer. Examples, parables, and illustrations are given from experience and the practice of missionary discipleship. There is a particular emphasis on means of grace and the spiritual disciplines outlined by St. Ignatius of Loyola. The conclusions point to a focus on prayer in the planning, preparation, and programming for the 2018 Conference.
The Legacy, Leadership, and Hope of Pan‐African Women of Faith in Building Sustainable Just Communities as a Missional Focus
Authors: Walker‐Smith Angelique
Published: December 2016

Conceiving mission in relation to discipleship entails learning from the margins. This article analyzes the experience and self‐understanding of pan‐African women of faith. Especially in relation to and utilizing the methodology of the ongoing emphasis on an ecumenical “pilgrimage of justice and peace,” their vision of hope is examined under the headings of via positiva, via negativa, and via transformativa. The article concludes by detailing recent and future work of PAWEEN–the Pan African Womens Ecumenical Empowerment Network–in relation to the Sustainable Development Goals of the United Nations.