bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiarrhythmic activity in occlusion‐reperfusion model of 1‐(1H‐indol‐4‐yloxy)‐3‐{[2‐(2‐methoxyphenoxy)ethyl]amino} propan‐2‐ol and its enantiomers
Authors: Bednarski Marek , Otto Monika , Dudek Magdalena , Siwek Agata , Zygmunt Małgorzata , Knutelska Joanna , Nowiński Leszek , Groszek Grażyna , Sapa Jacek
Published: September 2015

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide, especially in developed countries. The most serious problem after myocardial infarction is reperfusion injury that manifests as functional impairment, arrhythmia, and accelerated progression of cell death in certain critically injured myocytes. Subsequently the infarcted myocardium develops features of necrosis and reactive inflammation. To reduce lethal reperfusion injury in patient with AMI antioxidants, anti‐inflammatory agents, adenosine, opioids, metabolic modulators (glucose, insulin, and potassium, nicorandil and agents which reduce intracellular Ca2+ overload and inhibit Na+‐H+ exchange) are used. In this study a novel compound (compound 9) 1‐(1 h‐indol‐4‐yloxy)‐3‐{[2‐(2‐methoxyphenoxy) ethyl]amino}propan‐2‐ol and its enantiomers are examined in arrhythmia associated with coronary artery occlusion and reperfusion in a rat model. Antioxidant properties are also determined for test compounds using the malondialdehyde (MDA) lipid peroxidation and ferric reducing antioxidant power (FRAP) tests. In summary, the tested compounds, especially the S enantiomer has a strong antiarrhythmic activity in a model of occlusion and reperfusion of the left coronary artery which is probably related to their adrenolytic action. In contrast to carvedilol, none of the test compound reduced the lipid peroxidation but increased ferric reducing antioxidant power. In the antioxidant effect, there was no difference between the optical forms of compound 9.
Oxygen‐glucose deprivation preconditioning protects neurons against oxygen‐glucose deprivation/reperfusion induced injury via bone morphogenetic protein‐7 mediated ERK, p38 and Smad signalling pathways
Authors: Guan Junhong , Du Shaonan , Lv Tao , Qu Shengtao , Fu Qiang , Yuan Ye
Published: September 2015

Bone morphogenetic protein (BMP)‐7 mediated neuroprotective effect of cerebral ischemic preconditioning (IPC) has been studied in an ischemic animal model, but the underlying cellular mechanisms have not been clearly clarified. In this study, primary cortical neurons and the SH‐SY5Y cell line were used to investigate the role of BMP‐7 and its downstream signals in the neuroprotective effects of oxygen‐glucose deprivation preconditioning (OGDPC). Immunocytochemistry was used to detect the expression of neurofilament in neurons. MTT and lactate dehydrogenase activity assays were used to measure the cytotoxicity. Western blot was used to detect the protein expression of BMP‐7 and downstream signals. BMP inhibitor, mitogen‐activated protein kinase inhibitors, Smad inhibitor and siRNA of Smad 1 were used to investigate the role of corresponding signalling pathways in the OGDPC. Results showed that OGDPC‐induced overexpression of BMP‐7 in primary cortical neurons and SH‐SY5Y cells. Both of endogenous and exogenous BMP‐7 could replicate the neuroprotective effects seen in OGDPC pretreatment. In addition, extracellular regulated protein kinases, p38 and Smad signalling pathway were found to be involved in the neuroprotective effects mediated by OGDPC via BMP‐7. This study primarily reveals the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia.
Tobacco denormalisation and representations of different tobacco users in Norway: a cross‐sectional study
Authors: Sæbø Gunnar
Published: September 2015

This study asks whether representations of different typical tobacco users vary in line with established stereotypes and by social group membership (especially tobacco user status). Social identity theory posits that representations differ due to varying identification with product users on the basis of personal use, while distinction theory suggests representations will be structured by proximity and distance to user groups. Using principal component analysis to identify representations and regression analysis to determine variances in representations, we find that four of five groups of typical tobacco users (snus users, pipe, cigarette, and cigar smokers) can be classified according to three similar representations: socially secure, culturally marginal and unappealing. Respondents who themselves use a certain tobacco product are more likely to consider a ‘typical’ user from their own group as more ‘socially secure’ and less ‘culturally marginal’ and ‘unappealing’ than non‐users. Former smokers tend to side with non‐smokers, which suggests their ‘smoker identity’ is on the wane. At the representational level, then, socio‐historical distinctions between different tobacco products seem to have diminished in favour of a largely dual classification, with users expressing positive and non‐users negative representations, of any typical user. This is a likely consequence of persistent tobacco denormalisation policies.
Clinical Effects of a Longer Duration of Polymyxin B‐Immobilized Fiber Column Direct Hemoperfusion Therapy for Severe Sepsis and Septic Shock
Authors: Yamashita Chizuru , Hara Yoshitaka , Kuriyama Naohide , Nakamura Tomoyuki , Nishida Osamu
Published: September 2015

Polymyxin B‐immobilized fiber column direct hemoperfusion (PMX‐DHP) therapy is widely used for the treatment of severe sepsis and septic shock, and is generally performed for 2 h. Although previous studies demonstrated the efficacy of PMX‐DHP therapy, it currently remains unclear whether its optimal duration is 2 h. This retrospective study analyzed 37 patients with septic shock who showed a poor clinical response to 2 h of PMX‐DHP, and underwent a longer duration of this therapy. The mean duration of PMX‐DHP therapy was 15.8 ± 7.9 h, and none of the patients developed adverse events, which enabled the therapy to be performed safely. The pressure catecholamine index [CAIP = catecholamine index/mean arterial pressure; catecholamine index = dopamine + dobutamine + (adrenaline + noradrenaline) × 100 μg/kg per min], as an indicator of hemodynamics, improved significantly in the survival group in the period between the start and 24 h after the end of PMX‐DHP therapy (P < 0.01), and between 2 h after the start of and the end of this therapy (P < 0.05). In addition, the P/F ratio improved significantly in the group of surviving patients with acute respiratory distress syndrome (ARDS) in the period between the start and 24 h after the end of PMX‐DHP therapy (P < 0.01), and between 2 h after the start of and the end of this therapy (P < 0.01). These results suggest that a longer duration of PMX‐DHP therapy can be expected to improve the hemodynamics and pulmonary oxygenation capacity of patients with severe sepsis/septic shock. Strict prospective studies are needed in the future.
Granulocyte and Monocyte Adsorption Apheresis for Generalized Pustular Psoriasis: Therapeutic Outcomes in Three Refractory Patients
Authors: Fujisawa Tomomi , Suzuki Satoko , Mizutani Yoko , Doi Tomoaki , Yoshida Shozo , Ogura Shinji , Seishima Mariko
Published: September 2015

Generalized pustular psoriasis (GPP) is a type of neutrophilic dermatosis that is sometimes resistant to medications. In patients with neutrophilic skin diseases, granulocyte and monocyte adsorption apheresis (GMA) has been demonstrated to selectively and efficiently eliminate myeloid‐lineage leukocytes from the peripheral blood. We evaluated the efficacy and safety of repeated GMA therapy in three refractory GPP patients. Three GPP patients refractory to previous therapies received weekly GMA with five sessions per course, which was repeated when the symptoms reappeared. The efficacy was assessed by the disease severity scores 2 weeks after each course of GMA. The GPP severity scores of all three patients were reduced in all courses (N = 9); they were reduced by more than 3 points in six courses and by 2 points in three courses. After the first GMA course, the GPP severity scores were reduced by more than 3 points in all three patients. On average, the GPP severity scores were reduced by 4.67 and 3.67 points after the first course and repeated courses, respectively. The severity of edema and pustules were particularly improved in all patients and no adverse effects were observed. GMA showed efficacy for the treatment of refractory GPP patients as a non‐pharmacologic intervention without any associated adverse effects, and was particularly effective in the first course, but also effective in the subsequent courses.
Plasma Adiponectin Levels in Acute Liver Failure Patients Treated with Plasma Filtration with Dialysis and Plasma Exchange
Authors: Yamamoto Hiroshi , Nakae Hajime , Uji Yoshitaka , Maeda Kazuhisa , Tani Tohru , Eguchi Yutaka
Published: September 2015

Plasma filtration with dialysis (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside of the hollow fibers. Improvement of hypoadiponectinemia is considered to be a useful therapeutic approach for ameliorating fatal conditions including cardio‐metabolic and infectious disease. We investigated the effects of PDF in comparison to PE in terms of plasma adiponectin (APN) changes in patients with acute liver failure. Seventeen patients with liver failure were studied; PDF was performed 55 times and PE 14 times. Plasma APN levels increased significantly after PDF, while decreasing significantly after PE. PDF appears to be among the most useful blood purification therapies in acute liver failure cases in terms of increasing APN levels.
Low‐Density Lipoprotein Apheresis Ameliorates Renal Prognosis of Cholesterol Crystal Embolism
Authors: Ishiyama Katsuya , Sato Toshinobu , Taguma Yoshio
Published: September 2015

Drugs such as corticosteroids and statins have been used to treat cholesterol crystal embolism (CCE), but the prognosis remains poor. This study evaluated the efficacy of low‐density lipoprotein apheresis (LDL‐A) in patients with CCE. Patients with CCE who showed renal deterioration after vascular interventions were studied retrospectively. Information on demographic variables, clinical measurements, and medication use was collected. The outcomes were incidence of maintenance dialysis and mortality at 24 weeks. A total of 49 patients with CCE were included, among whom 37 (76%) were diagnosed pathologically and the remainder were diagnosed clinically. The median estimated GFR at baseline and at diagnosis were 40.5 and 13.4 mL/min per 1.73 m2, respectively. Corticosteroids were used in 42 patients (86%), statins in 30 patients (61%), and angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers in 29 patients (59%). LDL‐A was performed in 25 patients (LDL‐A group), and not in 24 patients (control group). Smoking (100% vs. 72%, P = 0.02), white blood cell count (8900/mm3 vs. 7000/mm3) and corticosteroid use (96% vs. 75%) were higher in the LDL‐A group compared with the control group, but there were no differences in other demographic and clinical parameters between the groups. Patients in the LDL‐A group had a lower incidence of maintenance dialysis (2/25 (8%) vs. 8/24 (33%), P < 0.05), and a trend towards lower mortality (2/25 (8%) vs. 7/24 (29%), P = 0.074). These results suggest that LDL‐A decreases the risk of maintenance dialysis in severe renal CCE patients after vascular interventions.
Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange
Authors: Ohkubo Atsushi , Okado Tomokazu , Kurashima Naoki , Maeda Takuma , Arai Shingo , Miyamoto Satoko , Itagaki Ayako , Seshima Hiroshi , Iimori Soichiro , Naito Shotaro , Sohara Eisei , Uchida Shinichi , Rai Tatemitsu
Published: September 2015

Selective plasma exchange (SePE) using a selective membrane separator is a modified method of simple plasma exchange (PE). Immunoglobulin G (IgG) subclass distribution is one of the important immunological characteristics of IgG. However, there is little information regarding the removal characteristics of IgG subclasses by SePE and conventional PE. Here, we investigated the removal ratio of IgG subclasses by PE and SePE in seven patients with immunological disorders. When the mean processed volume was 0.88 plasma volume (PV) (corresponding to 2.12 L), the mean percent reductions by PE were as follows: IgG, 63.2%; IgG1, 64.5%; IgG2, 64.0%; IgG3, 61.4%; and IgG4, 69.5%. When the mean processed volume was 1.18 PV (corresponding to 2.98 L), the mean percent reductions by SePE were as follows: IgG, 51.6%; IgG1, 55.3%; IgG2, 52.0%; IgG3, 53.7%; and IgG4, 64.6%. In both PE and SePE, using albumin solution as the supplementary fluid, IgG was effectively eliminated regardless of IgG subclasses.
Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis
Authors: Sandhya Pulukool , Danda Debashish , Sharma Disha , Scaria Vinod
Published: September 2015

The human body is an environmental niche which is home to diverse co‐habiting microbes collectively referred as the human microbiome. Recent years have seen the in‐depth characterization of the human microbiome and associations with diseases. Linking of the composition or number of the human microbiota with diseases and traits date back to the original work of Elie Metchnikoff. Recent advances in genomic technologies have opened up finer details and dynamics of this new science with higher precision. Microbe‐rheumatoid arthritis connection, largely related to the gut and oral microbiomes, has showed up as a result – apart from several other earlier, well‐studied candidate autoimmune diseases. Although evidence favouring roles of specific microbial species, including Porphyromonas, Prevotella and Leptotricha, has become clearer, mechanistic insights still continue to be enigmatic. Manipulating the microbes by traditional dietary modifications, probiotics, and antibiotics and by currently employed disease‐modifying agents seems to modulate the disease process and its progression. In the present review, we appraise the existing information as well as the gaps in knowledge in this challenging field. We also discuss the future directions for potential clinical applications, including prevention and management of rheumatoid arthritis using microbial modifications.
Least Squares Sparse Principal Component Analysis: A Backward Elimination Approach to Attain Large Loadings
Authors: Merola Giovanni Maria
Published: September 2015

Sparse principal components analysis (SPCA) is a technique for finding principal components with a small number of non‐zero loadings. Our contribution to this methodology is twofold. First we derive the sparse solutions that minimise the least squares criterion subject to sparsity requirements. Second, recognising that sparsity is not the only requirement for achieving simplicity, we suggest a backward elimination algorithm that computes sparse solutions with large loadings. This algorithm can be run without specifying the number of non‐zero loadings in advance. It is also possible to impose the requirement that a minimum amount of variance be explained by the components. We give thorough comparisons with existing SPCA methods and present several examples using real datasets.
Face‐down or no face‐down posturing following macular hole surgery: a meta‐analysis
Authors: Hu Zizhong , Xie Ping , Ding Yuzhi , Zheng Xinhua , Yuan Dongqing , Liu Qinghuai
Published: September 2015

Purpose

To evaluate the impact of postoperative posturing with or without face‐down on the anatomical and functional outcomes of macular hole surgery.

Methods

A literature‐based meta‐analysis was conducted to identify studies relevant to posturing following macular hole surgery (MHS). PubMed and Web of Science databases were used to retrieve articles up to 1 June 2015. The primary measures included MH closure and ideal vision acuity improvement. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in Review Manager.

Results

Four randomized control trials (RCTs) comprising 251 cases were included in the final meta‐analysis. No face‐down posturing (FDP) after MHS revealed lower anatomic success rate compared to face‐down posturing (OR = 0.33, 95% CI [0.13, 0.81], p = 0.02). For holes smaller than 400 μm in size, the subgroup meta‐analysis indicated no significant effect of FDP on successful hole closure (OR = 0.29, 95% CI [0.01, 7.34], p = 0.45). However, when holes were larger than 400 μm, it seemed less effective on MH closure following surgery in no FDP group (OR = 0.23, 95% CI [0.07, 0.71]), and this was statistically significant (p = 0.01).

Conclusions

Our work found that no FDP was not inferior to its face‐down counterpart for the success of MHS when macular holes were smaller than 400 μm in size. For macular holes larger than 400 μm, statistical analysis proved that FDP might be necessary. More well‐conducted randomized control trials are needed to verify our findings.
Geographies of marketisation in English higher education: territorial and relational markets and the case of undergraduate student fees
Authors: Hall Sarah
Published: September 2015

In this paper, I use the case of the marketisation of higher education in England to contribute to the growing interest in placing markets, and processes of market making, more centrally within economic geographical research agendas. In particular, my argument focuses on the spatiality of marketisation through the specific case of the introduction of undergraduate student fees in England from 1998 onwards. I argue that the marketisation of English higher education has operated, implicitly at least, with a territorial logic in which students fees are justified through an assumption that the value of a degree from an English university will arise from graduate salary premiums in domestic graduate labour markets. However, I demonstrate how English higher education overflows this territorial framing through the internationalisation of student choice and graduate labour markets in ways that challenge the marketisation process itself. This analysis reveals the hitherto comparatively neglected role of extra‐territorial relations in marketisation and the importance of these geographies for the future marketisation of higher education.
MalignantTFE3-rearranged perivascular epithelioid cell neoplasm (PEComa) presenting as a subcutaneous mass
Authors: Shon W. , Kim J. , Sukov W. , Reith J.
Published: September 2015

Perivascular epithelioid cell neoplasms (PEComas) are a group of mesenchymal tumours with concurrent melanocytic and myogenic differentiation. Although many cases are sporadic, PEComas can be associated with tuberous sclerosis. A distinct subset of deep-seated PEComas has been shown to carry TFE3 fusions. To our knowledge, this is the first reported case of primary subcutaneous malignant PEComa with molecular confirmation of TFE3 gene rearrangement.
Leadership and gender in groups: An experiment
Authors: Grossman Philip J. , Komai Mana , Jensen James E.
Published: September 2015

We conduct a laboratory experiment to study gender differences in leadership. We strip the concept of leadership down to its most basic elements. Questions of style and evaluations of a leader based on style of leadership adopted are made irrelevant. Our leader is an average player who is distinguished merely by occupying the leadership position. Legitimacy is conferred on the leader by the special information possessed. Followers voluntarily choose whether or not to follow the better‐informed leader. The effectiveness of the leader is reduced to two simple factors: is the leader willing or not to voluntarily place him/herself in a vulnerable position to achieve an outcome beneficial to both the leader and his/her followers? Do followers trust their leaders to make the right choice? We provide experimental evidence that female leaders and followers are more cooperative than the males in most circumstances. Female leaders show a hesitation to lead in mixed‐gender environments with gender signalling in circumstances where followers' refusal to follow can significantly hurt them. The behaviour of the followers is the same toward the leaders regardless of their gender.
Valproic Acid Modifies Synaptic Structure and Accelerates Neurite Outgrowth Via the Glycogen Synthase Kinase‐3β Signaling Pathway in an Alzheimer's Disease Model
Authors: Long Zhi‐Min , Zhao Lei , Jiang Rong , Wang Ke‐Jian , Luo Shi‐Fang , Zheng Min , Li Xiao‐Feng , He Gui‐Qiong
Published: September 2015

Aim

Tau hyperphosphorylation and amyloid β‐peptide overproduction, caused by altered localization or abnormal activation of glycogen synthase kinase‐3β (GSK‐3β), is a pathogenic mechanism in Alzheimer's disease (AD). Valproic acid (VPA) attenuates senile plaques and neuronal loss. Here, we confirmed that VPA treatment improved spatial memory in amyloid precursor protein (APP)/presenilin 1 (PS 1) double‐transgenic mice and investigated the effect of VPA on synaptic structure and neurite outgrowth.

Methods

We used ultrastructural analysis, immunocytochemistry, immunofluorescence staining, and Western blot analysis to assess the effect of VPA treatment in mice.

Results

VPA treatment thickened the postsynaptic density, increased the number of presynaptic vesicles, and upregulated the expression of synaptic markers PSD‐95 and GAP43. VPA increased neurite length of hippocampal neurons in vivo and in vitro. In VPA‐treated AD mouse brain, inactivated GSK‐3β (pSer9‐GSK‐3β) was markedly increased, while hyperphosphorylation of tau at Ser396 and Ser262 was decreased; total tau levels remained similar. VPA treatment notably improved pSer133‐cAMP response element‐binding protein (CREB) and brain‐derived neurotrophic factor (BDNF) levels, which are associated with synaptic function and neurite outgrowth.

Conclusion

VPA improves behavioral deficits in AD, modifies synaptic structure, and accelerates neurite outgrowth, by inhibiting the activity of GSK‐3β, decreasing hyperphosphorylated tau, enhancing CREB and BDNF expression.
Synaptic Plasticity and Signal Transduction Gene Polymorphisms and Vulnerability to Drug Addictions in Populations of European or African Ancestry
Authors: Levran Orna , Peles Einat , Randesi Matthew , Correa da Rosa Joel , Ott Jurg , Rotrosen John , Adelson Miriam , Kreek Mary Jeanne
Published: September 2015

Aim

Drug addiction is characterized, in part, by deregulation of synaptic plasticity in circuits involved in reward, stress, cue learning, and memory. This study was designed to assess whether 185 variants in 32 genes central to synaptic plasticity and signal transduction contribute to vulnerability to develop heroin and/or cocaine addiction.

Methods

Analyses were conducted in a sample of 1860 subjects divided according to ancestry (African and European) and drug of abuse (heroin or cocaine).

Results

Eighteen SNPs in 11 genes (CDK5R1, EPHA4, EPHA6, FOSL2, MAPK3, MBP, MPDZ, NFKB1, NTRK2, NTSR1, and PRKCE) showed significant associations (P < 0.01), but the signals did not survive correction for multiple testing. SNP rs230530 in the NFKB1 gene, encoding the transcription regulator NF‐kappa‐B, was the only SNP indicated in both ancestry groups and both addictions. This SNP was previously identified in association with alcohol addiction. SNP rs3915568 in NTSR1, which encodes neurotensin receptor, and SNP rs1389752 in MPDZ, which encodes the multiple PDZ domain protein, were previously associated with heroin addiction or alcohol addiction, respectively.

Conclusions

The study supports the involvement of genetic variation in signal transduction pathways in heroin and cocaine addiction and provides preliminary evidence suggesting several new risk or protective loci that may be relevant for diagnosis and treatment success.
Too Big to Jail? Company Status and Judicial Bias in an Emerging Market
Authors: Choi Hansoo , Kang Hyung‐Goo , Kim Woojin , Lee Changmin , Park Jongsik
Published: September 2015

Manuscript Type

Empirical

Research Question/Issue

This paper examines prosecutorial and judicial decisions to incarcerate the suspect upon indictment or conviction of embezzlement or breach of fiduciary duty in Korean firms. Our aim is to evaluate whether the judicial system is biased in favor of large business groups or chaebols in criminal cases.

Research Findings/Insights

Using a sample of 84 indictments and 78 convictions for embezzlement or breach of duty against managers of publicly traded firms in Korea between 2004 and 2008, we find that the probability of incarceration is much smaller if the indicted are associated with large business groups or large firms. In non‐large business group firms, initial disclosure of such accusation results in an average loss of a quarter of market value, and three quarters of convicted individuals are eventually removed from managerial positions. However, we observe neither such a loss nor turnover in large business group member firms.

Theoretical/Academic Implications

We identify a new determinant of judicial bias, namely the status of the company, in addition to individual‐level social status or class that has been examined in the previous literature. Such bias may reflect potential future career concerns of the prosecutors and judges who later become lawyers. The results also suggest that an additional motivation behind empire building or size‐maximizing behavior of top management is to effectively implement a legal strategy, a form of non‐market strategy.

Practitioner/Policy Implications

Corporate managers may apply our findings to manage legal risks and to formulate nonmarket strategies. However, biases in individual sentences may create system risk and economy‐wide inefficiencies. In order to reform the legal system, policymakers should take into account the externalities in individual sentencing decisions.
Proposal for an algorithm for liver transplantation in Caroli's disease and syndrome: putting an uncommon effort into a common task
Authors: Lai Quirino , Lerut Jan
Published: September 2015

Liver transplantation (LT) represents an uncommon indication for Caroli's disease (CD) or syndrome (CS). Excellent results of LT have been reported as shown by recent multicentric European and American registry reports. Clear therapeutic flowcharts to adopt in these diseases are still lacking. This review aims at analyzing highlighting recent transplant experiences in this field and also at focusing on the role of LT in case‐specific comorbidities such as development of cholangiocellular cancer or renal failure are present.
Digital pathology: elementary, rapid and reliable automated image analysis
Authors: Bouzin Caroline , Saini Monika L , Khaing Kyi‐Kyi , Ambroise Jérôme , Marbaix Etienne , Grégoire Vincent , Bol Vanesa
Published: September 2015

Aims

Slide digitalization has brought pathology to a new era, including powerful image analysis possibilities. However, while being a powerful prognostic tool, immunostaining automated analysis on digital images is still not implemented worldwide in routine clinical practice.

Methods and results

Digitalized biopsy sections from two independent cohorts of patients, immunostained for membrane or nuclear markers, were quantified with two automated methods. The first was based on stained cell counting through tissue segmentation, while the second relied upon stained area proportion within tissue sections. Different steps of image preparation, such as automated tissue detection, folds exclusion and scanning magnification, were also assessed and validated. Quantification of either stained cells or the stained area was found to be correlated highly for all tested markers. Both methods were also correlated with visual scoring performed by a pathologist. For an equivalent reliability, quantification of the stained area is, however, faster and easier to fine‐tune and is therefore more compatible with time constraints for prognosis.

Conclusions

This work provides an incentive for the implementation of automated immunostaining analysis with a stained area method in routine laboratory practice.
Profile of killer cell immunoglobulin‐like receptor and its human leucocyte antigen ligands in dengue‐infected patients from Western India
Authors: Alagarasu K. , Bachal R. V. , Shah P. S. , Cecilia D.
Published: September 2015

Killer cell immunoglobulin‐like receptors (KIRs) regulate the activation of natural killer cells (NKs). Qualitative and quantitative differences in the type and the number of KIRs expressed on NK cells affect its activation which would influence the outcome of the disease. In this study, 114 hospitalized cases of dengue [82 dengue fever (DF) and 32 dengue haemorrhagic fever (DHF) cases] and 104 healthy controls (HC) without no known history of hospitalization for dengue‐like illness were investigated for their KIR gene profile to find out the association of KIR genes with dengue disease severity. KIR gene profile was investigated using duplex sequence‐specific priming polymerase chain reaction‐based typing system. The results revealed a higher frequency of KIR3DL1 gene [P = 0.0225; odds ratio (OR) 4.1 95% confidence interval (CI) 1.1–14.8] and lower frequency of KIR3DS1/3DS1 genotype [P = 0.0225; OR 0.24 95% CI (0.068–0.88)] in DF cases compared to HC. Immunoglobulin‐like receptor gene frequencies were not different between DHF and DF or HC. The results suggest that KIR3DL1/KIR3DS1 locus might be associated with the risk of developing DF.
Molecular Characterization of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in Captive Wildlife at Zhengzhou Zoo, China
Authors: Li Junqiang , Qi Meng , Chang Yankai , Wang Rongjun , Li Tongyi , Dong Haiju , Zhang Longxian
Published: September 2015

Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are common gastrointestinal protists in humans and animals. Two hundred and three fecal specimens from 80 wildlife species were collected in Zhengzhou Zoo and their genomic DNA extracted. Three intestinal pathogens were characterized with a DNA sequence analysis of different loci. Cryptosporidium felis, C. baileyi, and avian genotype III were identified in three specimens (1.5%), the manul, red‐crowned crane, and cockatiel, respectively. Giardia duodenalis was also found in five specimens (2.5%) firstly: assemblage B in a white‐cheeked gibbon and beaver, and assemblage F in a Chinese leopard and two Siberian tigers, respectively. Thirteen genotypes of E. bieneusi (seven previously reported genotypes and six new genotypes) were detected in 32 specimens (15.8%), of which most were reported for the first time. A phylogenetic analysis of E. bieneusi showed that five genotypes (three known and two new) clustered in group 1; three known genotypes clustered in group 2; one known genotype clustered in group 4; and the remaining four genotypes clustered in a new group. In conclusion, zoonotic Cryptosporidium spp., G. duodenalis, and E. bieneusi are maintained in wildlife and transmitted between them. Zoonotic disease outbreaks of these infectious agents possibly originate in wildlife reservoirs.
Shallow genetic divergence and species delineations in the endemic Labeobarbus species flock of Lake Tana, Ethiopia
Authors: Nagelkerke L. A. J. , Leon‐Kloosterziel K. M. , Megens H.‐J. , De Graaf M. , Diekmann O. E. , Sibbing F. A.
Published: September 2015

To assess whether the species distinctions of Lake Tana's Labeobarbus spp. are supported by genetic information, microsatellite markers were used. A total of 376 Labeobarbus spp., belonging to 24 populations of 11 species from three regions of the lake (north, south and east), were sampled. Eight microsatellite markers were analysed. In general, differences between conspecific populations were smaller than differences between populations of different species. For six species, conspecific populations from different regions in the lake were consistently more similar than populations of other species from the same region. For four species this was not the case, while for one species two populations were similar, but different from the third population. River‐spawning species appeared to be more distinct than presumed lake spawners. On the species level, there was a significant correlation between genetic and morphological differentiation, especially in morphological aspects associated with ecological functioning. This suggests that genetic differentiation arose together with adaptive radiation, although the overall genetic differentiation among the Lake Tana Labeobarbus spp. is small.
Strategic Choices at Entry and Relative Survival Advantage of Cooperatives versus Corporations in the US Bio‐Ethanol Industry, 1978‐2015
Authors: Boone Christophe , Özcan Serden
Published: September 2015

The sustainability of cooperatives versus corporations is hotly contested. We propose that strategic choices at entry can help to explain the endurance of these two governance modes. We hypothesize that cooperatives have a survival advantage if their major drawback – high coordination costs – is curbed by high levels of member engagement at founding. Our analysis of survival rates in the US bio‐ethanol industry shows that cooperatives outlive corporations (1) if investment size at founding is large (strong financial engagement), (2) if they enter de novo instead of de alio (strong product‐market engagement) and (3) if the cooperative venture has been carefully planned from the start (greenfield entry) instead of built upon the acquisition of an existing plant (strong venture‐building engagement). These findings caution against the view that a particular mode of governance is superior or inferior to another in all circumstances.
Enhancing Stock Market Return with New Product Preannouncements: The Role of Information Quality and Innovativeness
Authors: Lee Ruby P. , Chen Qimei , Hartmann Nathaniel N.
Published: September 2015

To advance development and application of signaling theory in the new product preannouncement literature while seeking to resolve ambiguity regarding the influence of innovativeness on stock market return, the role of information quality is examined. Specifically, this study investigates the effect of innovativeness across low and high levels of information quality. The results, ascertained using event study methodology on a sample of 243 new product preannouncements collected over a nine‐year period, indicate that higher information quality increases the strength of the positive relationship between innovativeness and stock market return. The findings offer managers insight into what role information quality plays in new product preannouncements that can help their firms generate higher stock market return.
When a liver biopsy is ‘normal’…
Authors: Prati Daniele , Colli Agostino
Published: September 2015

See Article on Page 119
Development of enzalutamide for metastatic castration‐resistant prostate cancer
Authors: Bhattacharya Suman , Hirmand Mohammad , Phung De , van Os Steve
Published: September 2015

Prostate cancer is the most prevalent cancer among men in the Western world and a leading cause of cancer‐related death among men. Within 5 years of initial diagnosis, approximately 10–20% of men will progress to metastatic castration‐resistant prostate cancer (mCRPC). Often characterized by increased prostate‐specific antigen and androgen receptor (AR) activity despite castrate levels of testosterone, mCRPC has a poor prognosis and causes significant deterioration in quality of life. Enzalutamide is an AR inhibitor approved to treat mCRPC in both post‐ and pre‐chemotherapy settings on the basis of results from two phase III randomized, placebo‐controlled trials, AFFIRM and PREVAIL, respectively. Enzalutamide significantly prolonged overall survival (hazard ratio (HR), AFFIRM 0.63, 95% confidence interval (CI) 0.53–0.75, P < 0.001; PREVAIL 0.71, 95% CI 0.60–0.84, P < 0.001) and radiographic progression (HR, AFFIRM 0.40, 95% CI 0.35–0.47, P < 0.001; PREVAIL 0.19, 95% CI 0.15–0.23, P < 0.001), and significantly improved quality of life. With an acceptable safety profile, enzalutamide is one of several emerging alternative options for men with mCRPC. Studies are ongoing to explore potential benefits of enzalutamide in earlier stages of prostate cancer and in breast cancer.
Novel anticoagulants: general overview and practical considerations for dental practitioners
Authors: Elad S , Marshall J , Meyerowitz C , Connolly G
Published: September 2015

Currently, 4 novel Direct Oral Anticoagulants (DOACs) were approved by the FDA. This review focuses on these agents and proposes a matrix for the general dentists to assess bleeding risk in dental management of patient on DOACs. The outline covers the pharmacology of DOACs (rivaroxaban, apixaban, edoxaban and dabigatran), bleeding complications, risk associated with discontinuation, monitoring/reversal, and implications for the dental practitioners. A total of 18 randomized controlled trials were identified with mixed results in regards to the risk for bleeding. Considering the pharmacology of DOACs and challenges in monitoring and reversing their effect, the dentist should consider carefully the management of patients on DOACs as it may differ from patients on conventional anticoagulants. Based on the type of dental procedure and the medical risk assessment, several general treatment approaches can be considered: continue DOACs, time dental treatment as late as possible after the last DOACs dose, discontinue DOACs for 24hrs, or discontinue DOACs for 48hrs. Based on the current reported dental literature, limited dental surgery may benefit from the first 2 conservative options. However, this needs to be proven in comparative clinical trials.
Rapid leaf development drives the seasonal pattern of volatile organic compound (VOC) fluxes in a ‘coppiced’ bioenergy poplar plantation
Authors: Brilli Federico , Gioli Beniamino , Fares Silvano , Terenzio Zenone , Zona Donatella , Gielen Bert , Loreto Francesco , Janssens Ivan A. , Ceulemans Reinhart
Published: September 2015

Leaves of fast‐growing, woody bioenergy crops often emit volatile organic compounds (VOC). Some reactive VOC (especially isoprene) play a key role in climate forcing and may negatively affect local air quality. We monitored the seasonal exchange of VOC using the eddy covariance technique in a ‘coppiced’ poplar plantation. The complex interactions of VOC fluxes with climatic and physiological variables were also explored by using an artificial neural network (Self Organizing Map). Isoprene and methanol were the most abundant VOC emitted by the plantation. Rapid development of the canopy (and thus of the leaf area index, LAI) was associated with high methanol emissions and high rates of gross primary production (GPP) since the beginning of the growing season, while the onset of isoprene emission was delayed. The highest emissions of isoprene, and of isoprene photo‐oxidation products (Methyl Vinyl Ketone and Methacrolein, iox), occurred on the hottest and sunniest days, when GPP and evapotranspiration were highest, and formaldehyde was significantly deposited. Canopy senescence enhanced the exchange of oxygenated VOC. The accuracy of methanol and isoprene emission simulations with the Model of Emissions of Gases and Aerosols from Nature increased by applying a function to modify their basal emission factors, accounting for seasonality of GPP or LAI.
Impact Factors and Risk Analysis of Tropical Cyclones on a Highway Network
Authors: Yang Saini , Hu Fuyu , Jaeger Carlo
Published: September 2015

Coastal areas typically have high social and economic development and are likely to suffer huge losses due to tropical cyclones. These cyclones have a great impact on the transportation network, but there have been a limited number of studies about tropical‐cyclone‐induced transportation network functional damages, especially in Asia. This study develops an innovative measurement and analytical tool for highway network functional damage and risk in the context of a tropical cyclone, with which we explored the critical spatial characteristics of tropical cyclones with regard to functional damage to a highway network by developing linear regression models to quantify their relationship. Furthermore, we assessed the network's functional risk and calculated the return periods under different damage levels. In our analyses, we consider the real‐world highway network of Hainan province, China. Our results illustrate that the most important spatial characteristics were location (in particular, the midlands), travel distance, landfalling status, and origin coordinates. However, the trajectory direction did not obviously affect the results. Our analyses indicate that the highway network of Hainan province may suffer from a 90% functional damage scenario every 4.28 years. These results have critical policy implications for the transport sector in reference to emergency planning and disaster reduction.
Public Discourses About International Students
Authors: Yi Joseph E. , Jung Gowoon
Published: September 2015

A growing, English‐language literature analyzes the public discourse of international education and students. One large set of studies highlight the discursive marginalization of non‐western, international students in western, host societies. They draw on critical discourse analysis (CDA) and meta‐narratives of western, White, and elite dominance, which diminish the theoretical importance of discourse in non‐western and non‐elite settings. A second, smaller set of studies analyze the public discourse of international education in non‐western, specifically Asian, countries; they generally reference educational discourse in both Asian and western countries. Relatively few studies critically examine patterns of discursive domination in Asian discourse; but the ones that do so compare both Asian and Western countries. Even rarer are studies of social media discourse among international students. We find a few studies of social media discourse among Asian students who studied abroad, but none of foreign students studying in host, Asian countries. Attention to multiple discourses and theoretical narratives offers a fruitful, research agenda and underlines the complex, dynamic, global nature of contemporary public discourse on international education.
Normative Accountability: How the Medical Model Influences Transgender Identities and Experiences
Authors: Johnson Austin H.
Published: September 2015

The medicalization of gender variance is a key force in transgender people's experiences of embodiment, identity, and community. While most directly dictating experiences of diagnosis and medical classification, it is important to acknowledge that the effects of medicalization are widespread across social contexts and institutions. I explore the medical model of transgender identity, with special attention to its current diagnostic classification, in order to highlight how transgender people's interactional experiences of gender are shaped by medical authority. I review literature that highlights the operation of the medical model as a normative accountability structure in its influence across multiple institutions of social life including health and healthcare, transgender community groups, and legal classification.
Organizational Political Economy and Environmental Pollution
Authors: Prechel Harland
Published: September 2015

Environmental scholars have made important progress explaining the social forces associated with pollution. Although important exceptions exist, insufficient attention has been given to organizations, which is where most environmental pollution is produced. Even less attentions has been given to parent companies, which have ultimate decision‐making authority over their polluting facilities. To file this gap in the literature, this paper develops an organizational political economy perspective to advance our understanding of how organizational and political‐legal arrangements affect parent companies' capacity to externalize their pollution costs to society. Organizational political economy maintains that corporations' organizational complexity, financial characteristics, management operating systems, political embeddedness in subnational states, and the degree of compliance with national and subnational environmental policies affect their capacity to externalize pollution costs. This perspective also shows how the exercise of organizational power to externalize pollution costs subsidizes the managerial and investor classes by the middle and working classes, whose taxes pay for a large share of environmental clean‐up costs, thereby contributing to economic inequality that goes beyond standard inequality measurements.
Extreme‐phenotype genome‐wide association study (XP‐GWAS): a method for identifying trait‐associated variants by sequencing pools of individuals selected from a diversity panel
Authors: Yang Jinliang , Jiang Haiying , Yeh Cheng‐Ting , Yu Jianming , Jeddeloh Jeffrey A. , Nettleton Dan , Schnable Patrick S.
Published: September 2015

Although approaches for performing genome‐wide association studies (GWAS) are well developed, conventional GWAS requires high‐density genotyping of large numbers of individuals from a diversity panel. Here we report a method for performing GWAS that does not require genotyping of large numbers of individuals. Instead XP‐GWAS (extreme‐phenotype GWAS) relies on genotyping pools of individuals from a diversity panel that have extreme phenotypes. This analysis measures allele frequencies in the extreme pools, enabling discovery of associations between genetic variants and traits of interest. This method was evaluated in maize (Zea mays) using the well‐characterized kernel row number trait, which was selected to enable comparisons between the results of XP‐GWAS and conventional GWAS. An exome‐sequencing strategy was used to focus sequencing resources on genes and their flanking regions. A total of 0.94 million variants were identified and served as evaluation markers; comparisons among pools showed that 145 of these variants were statistically associated with the kernel row number phenotype. These trait‐associated variants were significantly enriched in regions identified by conventional GWAS. XP‐GWAS was able to resolve several linked QTL and detect trait‐associated variants within a single gene under a QTL peak. XP‐GWAS is expected to be particularly valuable for detecting genes or alleles responsible for quantitative variation in species for which extensive genotyping resources are not available, such as wild progenitors of crops, orphan crops, and other poorly characterized species such as those of ecological interest.
Pim kinases modulate resistance to FLT3 tyrosine kinase inhibitors in FLT3-ITD acute myeloid leukemia
Authors: Green Alexa S. , Maciel Thiago T. , Hospital Marie-Anne , Yin Chae , Mazed Fetta , Townsend Elizabeth C. , Pilorge Sylvain , Lambert Mireille , Paubelle Etienne , Jacquel Arnaud , Zylbersztejn Florence , Decroocq Justine , Poulain Laury , Sujobert Pierre , Jacque Nathalie , Adam Kevin , So Jason C. C. , Kosmider Olivier , Auberger Patrick , Hermine Olivier , Weinstock David M. , Lacombe Catherine , Mayeux Patrick , Vanasse Gary J. , Leung Anskar Y. , Moura Ivan C. , Bouscary Didier , Tamburini Jerome
Published: September 2015

Synergy between FLT3 and Pim kinase inhibition in acute myeloid leukemia with FLT3-ITD mutation.
Polya’s bees: A model of decentralized decision-making
Authors: Golman Russell , Hagmann David , Miller John H.
Published: September 2015

A mathematical model helps explain how the complex social systems of ants and bees make collective decisions.
Organic printed photonics: From microring lasers to integrated circuits
Authors: Zhang Chuang , Zou Chang-Ling , Zhao Yan , Dong Chun-Hua , Wei Cong , Wang Hanlin , Liu Yunqi , Guo Guang-Can , Yao Jiannian , Zhao Yong Sheng
Published: September 2015

Flexible organic photonic devices for high-performance optical information processing can be produced via ink-jet printing.