bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 3‐methyladenine on isolated left atria subjected to simulated ischaemia–reperfusion
Authors: Hermann Romina , Vélez Débora Elisabet , Rusiecki Tatiana Mariel , Fernández Pazos María de las Mercedes , Mestre Cordero Victoria Evangelina , Marina Prendes María Gabriela , Perazzo Rossini Juan Carlos , Savino Enrique Alberto , Varela Alicia
Published: October 2014

Although autophagy is a prominent feature of myocardial ischaemia and reperfusion, its functional significance is unclear and controversial. In order to gain a deeper insight into the role of autophagy in myocardial ischaemia‐reperfusion, we explored the effects of the pharmacological inhibitor of autophagy 3‐methyladenine (3‐MA). Isolated rat atria subjected to simulated 75‐min ischaemia/75‐min reperfusion (Is‐Rs) in the presence or absence of 3‐MA were used. The LC3‐II/LC3‐I ratio, an indicator of autophagosome formation, did not increase after ischaemia either in the presence or absence of 3‐MA, but there was significant enhancement during reperfusion, which was prevented by the presence of 3‐MA. The autophagy inhibitor also increased p62 protein, one of the specific substrates degraded through the autophagy‐lysosomal pathway. Electron micrographs showed double membrane autophagosome‐like structures during reperfusion, which were absent in atria subjected to Is‐Rs in the presence of 3‐MA. These findings suggest that this agent inhibited the autophagic flux under the present experimental conditions. Inhibition of autophagy during Is‐Rs was accompanied by a high incidence of tachyarrhythmias during reperfusion, and a decrease in the maximal inotropic response to β‐adrenergic and to calcium stimulation at the end of Is‐Rs. Deterioration of mitochondrial morphology and function, without affecting cell viability, was observed in atria subjected to Is‐Rs in the presence of 3‐MA. The present results suggest an association between the inhibition of autophagy and functional alterations of the cells that have undergone sublethal stress, and have been able to recover in this experimental model of ischaemia–reperfusion.
Should the individual preterm birth risk be incorporated into the embryo transfer policy in in vitro fertilisation? A decision analysis
Authors: Kamphuis EI , van Wely M , Repping S , van der Veen F , de Groot CJM , Hompes P , Mol BWJ , Kazemier BM
Published: October 2014

Objective

To assess by proof of principle whether the individual risk for preterm birth (PTB) should be incorporated into the embryo transfer policy in in vitro fertilisation (IVF).

Design and setting

A theoretical decision analysis.

Methods and main outcome measures

A decision tree was built to compare the consequences of different chances of PTB on the outcome of single embryo transfer (SET) or double embryo transfer (DET) in patients with different prognosis of conception. Based on patient characteristics, three scenarios of prognosis of conception were considered and the consequences of SET and DET were calculated for different chances of PTB in these groups. The primary outcome was the health of the children born. Sensitivity analyses were performed for both prognosis for conception and chances of PTB.

Results

In women with good fertility prospects, one IVF cycle with DET increases the ongoing pregnancy rate (OPR) from 29 to 39% compared with SET, whereas the chances of poor neonatal outcome in these extra pregnancies range from 1.4 to 11% per pregnancy depending on the individual PTB risk. However, for women with poor fertility prospects, DET increases the OPR from 8 to 11% with minimal additional poor neonatal outcome, ranging from 0.3 to 4.0% per pregnancy for women with a low or high PTB risk, respectively. Our findings were robust in multiple sensitivity analyses.

Conclusion

In an IVF programme, the optimal embryo transfer strategy is dependent on the singleton and multiple pregnancy chances of a woman, but also on her PTB risk. In women with low PTB risk, DET increases the OPR for a small additional risk of neonatal complications. Our analysis pleads for a tailored management strategy, taking into account the personalised prognosis for (multiple) pregnancy and PTB.
Degenerate slave‐makers, but nevertheless slave‐makers? Host worker relatedness in the ant Myrmoxenus kraussei
Authors: SUEFUJI Masaki , HEINZE Jürgen
Published: October 2014

Socially parasitic ants of the formicoxenine genus Myrmoxenus exhibit considerable diversity in colony structure and life history. While some species are active slave‐makers with many workers and others are workerless ‘murder‐parasites,’ Myrmoxenus kraussei is considered as a ‘degenerate slave‐maker’ because of its very low worker numbers. Here, we document that Temnothorax recedens host workers in single colonies of M. kraussei from Lago di Garda, Italy, exhibit significantly more genetic diversity than workers in unparasitized colonies. This raises the possibility that, despite its low worker numbers, M. kraussei may actively engage in slave raids in nature.
Acute alcohol use among suicide decedents in 14USstates: impacts of off‐premise and on‐premise alcohol outlet density
Authors: Giesbrecht Norman , Huguet Nathalie , Ogden Lauren , Kaplan Mark S. , McFarland Bentson H. , Caetano Raul , Conner Kenneth R. , Nolte Kurt B.
Published: October 2014

Aims

To estimate the association between per capita alcohol retail outlet density and blood alcohol concentration (BAC) from 51 547 suicide decedents and to analyse the relationship between alcohol outlet density and socio‐demographic characteristics among alcohol‐positive suicide decedents in theUnitedStates by racial/ethnic groups and method of suicide.

Design

Analysis ofUSdata, 2003–11,NationalViolentDeathReportingSystem.

Setting

Suicide decedents from 14USstates.

Participants

A total of 51 347 suicide decedents tested for BAC.

Measurements

BAC and levels were derived from coroner/medical examiner reports. Densities of county level on‐premises and off‐premises alcohol retail outlets were calculated using the 2010Census.

Findings

Multi‐level logistic regression models suggested that higher off‐premises alcohol outlet densities were associated with greater proportions of alcohol‐related suicides among men—for suicides with alcohol present [BAC>0; adjusted odds ratio (AOR) = 1.08, 95% confidence interval (CI) = 1.03–1.13]. Interactions between outlet density and decedents' characteristics were also tested. There was an interaction between off‐premises alcohol availability andAmericanIndian/AlaskaNative race (AOR = 1.36; 95%CI = 1.10–1.69) such that this subgroup had highestBACpositivity. On‐premises density was also associated withBAC>0 (AOR = 1.07; 95%CI = 1.03–1.11) andBAC≥0.08 (AOR = 1.05; 95%CI = 1.02–1.09) among male decedents.

Conclusions

In theUnited States, the density of both on‐ and off‐premises alcohol outlets in a county is associated positively with alcohol‐related suicide, especially amongAmericanIndians/AlaskaNatives.
“Our Goal Is Not to Punish but to Reconcile”: Mediation in Postgenocide Rwanda
Authors: Doughty Kristin C.
Published: October 2014

In this article, I explore what is at stake in embedding mediation efforts in legal forums backed by force across a wide range of disputes in postgenocide Rwanda as well as what is at stake in participants’ contestation over the terms of unity. Considering genocide courts, mediation committees, and a legal aid clinic in one analytic frame underscores continuities in both their top‐down social engineering goals and people's experience of the mediation focus across them. Building on Laura Nader's research to analyze the emphasis on harmony in these forums, I illustrate how mediation served as a technique of governance intended to reshape postgenocide Rwanda into a particular kind of community and how exhortations to unity were linked to broader forms of cultural control. I argue that although law‐based mediation was framed as benign and is often promoted by the transitional justice movement on the basis of local culture, its implementation always involves coercion and accompanying resistance. What emerges, I argue, is not the creation of idealistic state versions of national belonging, nor simply coercive silencing, but, rather, a space in which people contest the terms of community and shape new moral orders.
Political Economy, Ethnogenesis, and Language Dispersals in the Prehispanic Andes: A World‐System Perspective
Authors: Hornborg Alf
Published: October 2014

In this article, I argue, first, that a world‐system perspective can illuminate the role of prestigious trade goods such as Spondylus in the reproduction of pre‐Hispanic Andean societies and the significance of their procurement for the course of Andean prehistory. Second, I argue that the successive dispersals of major Andean languages (Aymara, Quechua, Pukina) reflect the establishment of prestigious lingua francas integrating such systems of long‐distance exchange. Political, agricultural, stylistic, and linguistic expansions in prehistory are interpreted as reflections of the integration of regional and interregional systems of exchange and interaction. The theoretical framework of world‐system analysis is shown not only to be applicable to the shifting economic and political geography of the pre‐Hispanic Andes but also to help account for a range of cultural phenomena that are generally not viewed from this perspective, including familiar details of Inca history such as Cuzco's relations to preexisting languages and ethnic identities. Rather than viewing the emergence of linguistic, stylistic, and other identity‐related homogeneities as consequences of political unification, I suggest that ethnolinguistic integration may precede efforts at political control.
Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients
Authors: Helin‐Toiviainen Minna , Rönkkö Seppo , Puustjärvi Tuomo , Rekonen Petri , Ollikainen Minna , Uusitalo Hannu
Published: October 2014

Purpose

Chronic conjunctival inflammation, caused by various reasons, for example long‐term use of topical drugs and/or their preservatives, affects the outcome of glaucoma surgery by interfering with wound healing. Matrix metalloproteinases (MMPs) remodel extracellular matrix (ECM) and are involved in the wound healing process. This study was designed to evaluate the conjunctival expression of MMPs and their tissue inhibitors (TIMPs) in the normal eye, primary open‐angle glaucoma (POAG) and exfoliation glaucoma (ExG) and whether there is an association between staining intensities and deep sclerectomy outcome.

Methods

Immunohistochemical procedures were performed on conjunctival samples which were obtained from POAG (n = 11) and ExG (n = 14) patients as well as normal (n = 7) subjects. Antibodies against MMPs (MMP‐1, ‐2, ‐3 and ‐9) and TIMPs (TIMP‐1, ‐2 and ‐3) were used.

Results

In conjunctival stroma, expression levels of MMP‐2 (p = 0.047), MMP‐3 (p = 0.009), MMP‐9 (p < 0.001), TIMP‐1 (p = 0.003), TIMP‐2 (p < 0.001) and TIMP‐3 (p < 0.001) in ExG and MMP‐9 (p = 0.008), TIMP‐2 (p = 0.02) and TIMP‐3 (p = 0.002) in POAG were significantly increased compared to control. We further found correlations between expression of MMP‐1 and MMP‐3 and the length of pilocarpine treatment.

Conclusion

The expression of MMPs and TIMPs is increased in the conjunctiva of POAG and ExG patients having a long history of topical antiglaucoma drops. Antiglaucoma agents and/or their preservatives alter the remodelling balance of ECM in conjunctiva of POAG and ExG eyes. The balance between MMPs and TIMPs may play a crucial role in the conjunctival wound healing process and the outcome of glaucoma surgery.
The incidence of hepatocellular carcinoma is reduced in patients with chronic hepatitis B on long‐term nucleos(t)ide analogue therapy
Authors: Coffin C. S. , Rezaeeaval M. , Pang J. X. , Alcantara L. , Klein P. , Burak K. W. , Myers R. P.
Published: October 2014

Background

North American data are lacking on the effect of nucleos(t)ide analogues (NA) in preventing chronic hepatitis B (CHB)‐related hepatocellular carcinoma (HCC).

Aim

To determine the incidence of HCC in NA‐treated patients and compare this risk with that predicted without treatment based on the REACH‐B model.

Methods

In this retrospective study, the incidence of HCC was determined in CHB patients initiated on NA from 1999 to 2012. Pre‐treatment data utilised in the REACH‐B model were used to predict the annual HCC risk. The standardised incidence ratio (SIR) for HCC was calculated by comparing the observed to expected number of cases, and HCC risk factors determined by Cox proportional hazards regression.

Results

Five hundred and forty nine initiated NA (14% lamivudine, 5% adefovir, 1.5% telbivudine, 39% entecavir, 41% tenofovir). Over a median follow‐up of 3.2 years (IQR 1.9–4.6), 11 (3.2%) were diagnosed with HCC. Among 322 with data to calculate the REACH‐B model, the median age at treatment initiation was 46 years (IQR 38–55), 65% were male, 32% HBeAg positive and 20% had cirrhosis. The median pre‐treatment ALT was 71 U/L (IQR 41–127) and HBV DNA was 6.48 log10 copies/mL (4.95–8.04). The observed annual HCC incidence (0.9%; 95% CI 0.5–1.7) was significantly lower than predicted without treatment by the REACH‐B model (SIR 0.46; 95% CI 0.23–0.82); this risk was reduced after 4 years of therapy (SIR 0.49; 95% CI 0.2–1.00).

Conclusions

In this Canadian study of nucleos(t)ide analogues‐treated patients with chronic hepatitis B, the incidence of HCC was lower than expected, suggesting that NA reduce the risk of chronic hepatitis B‐related HCC.
The prevention of pregnancy‐related venous thromboembolism
Authors: Guimicheva Boriana , Czuprynska Julia , Arya Roopen
Published: October 2014

Pregnancy‐related venous thromboembolism (VTE) remains one of the leading causes of maternal mortality and morbidity in the developed world. There is a lack of high‐level data surrounding the use of thromboprophylaxis in pregnancy. In the UK, following the publication of the first Royal College of Obstetricians and Gynaecologists (RCOG) guideline for VTE prophylaxis during pregnancy and the puerperium in 2004, a fall in maternal deaths secondary to VTE was observed during the subsequent triennium (2006–2008). For the first time since 1985, VTE was no longer the most common cause of maternal death. Low‐molecular‐weight‐heparin (LMWH) is generally the agent of choice for thromboprophylaxis in this setting, and is considered safe and efficacious. The accurate risk stratification of women in order to allow the targeted provision of thromboprophylaxis is challenging. A number of international guidelines support risk assessment for pregnancy‐related VTE and the provision of LMWH for those who are deemed at sufficiently high risk. This review describes the importance of VTE in pregnancy and the puerperium, the part played by different risk factors and the role of thromboprophylaxis in this group of patients.
Human renal tubular epithelial cells suppress alloreactive T cell proliferation
Authors: Demmers M W H J , Korevaar S S , Roemeling-van Rhijn M , van den Bosch T P P , Hoogduijn M J , Betjes M G H , Weimar W , Baan C C , Rowshani A T
Published: October 2014

Renal tubular epithelial cells (TECs) are one of the main targets of alloreactive T cells during acute rejection. We hypothesize that TECs modulate the outcome of alloimmunity by executing immunosuppressive effects in order to dampen the local inflammation. We studied whether TECs possess immunosuppressive capacities and if indoleamine 2,3-dioxygenase (IDO) might play a role in suppressing T cell alloreactivity. Next, we studied the role of programmed death ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1 with regard to TEC-related immunomodulatory effects. CD3/CD28 and alloactivated peripheral blood mononuclear cells were co-cultured with activated TECs. We analysed CD4+ and CD8+ T cell proliferation and apoptosis in the absence or presence of IDO inhibitor 1-methyl-L-tryptophan (1-L-MT), anti-PD-L1 and anti-ICAM-1. Further, we examined whether inhibition of T cell proliferation was cell–cell contact-dependent. We found that TECs dose-dependently inhibited CD4+ and CD8+ T cell proliferation (P < 0·05). Activated TECs showed significantly increased IDO activity and up-regulated PD-L1 and ICAM-1 expression. Suppressed CD4+ and CD8+ T cell proliferation was only partially restored or failed to restore using 1-L-MT. Activated TECs increased early and late apoptosis of proliferating CD4+ and CD8+ T cells; only CD4+ T cell apoptosis was statistically affected by 1-L-MT. Transwell experiments revealed that TEC-mediated immunosuppression is cell–cell contact-dependent. We found that anti-ICAM-1 affected only CD4+ T cell apoptosis and not T cell proliferation. Our data show that TECs suppress both CD4+ and CD8+ T cell proliferation contact dependently. Interestingly, inhibition of proliferation and enhancement of apoptosis of T cell subsets is differentially regulated by indoleamine 2,3-dioxygenase and ICAM-1, with no evidence for the involvement of PD-L1 in our system.
A Visualization Tool Used to Develop New Photon Mapping Techniques
Authors: Spencer B. , Jones M. W. , Lim I. S.
Published: October 2014

We present a visualization tool aimed specifically at the development and optimization of photon map denoising methods. Our tool allows the rapid testing of hypotheses and algorithms through the use of parallel coordinates, domain‐specific scripting, colour mapping and point plots. Interaction is carried out by brushing, adjusting parameters and focus‐plus‐context and yields interactive visual feedback and debugging information. We demonstrate the use of the tool to explore high‐dimensional photon map data, facilitating the discovery of novel parameter spaces which can be used to dissociate complex caustic illumination. We then show how these new parametrizations may be used to improve upon pre‐existing noise removal methods in the context of the photon relaxation framework.
Botanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Process
Authors: Zhao Jia , Cheng Yuan‐Yuan , Fan Wen , Yang Chuan‐Bin , Ye Shui‐Fen , Cui Wei , Wei Wei , Lao Li‐Xing , Cai Jing , Han Yi‐Fan , Rong Jian‐Hui
Published: October 2014

Aim

Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal‐regulated‐kinases (ERK) 1/2 and phosphoinositide‐3‐kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C‐glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process.

Methods

We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP‐lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2, and HO‐1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit.

Results

Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP‐lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10‐fold. Mechanistic studies revealed: (1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase‐1 (HO‐1) pathways; (2) ERK1/2, PI3K/Akt, and HO‐1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF‐induced neuritogenesis in a timing‐dependent manner.

Conclusion

Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin‐related compounds in neurodegenerative diseases.
Factors associated with conversion from laparoscopic to open colectomy using the National Surgical Quality Improvement Program (NSQIP) database
Authors: Bhama A. R. , Charlton M. E. , Schmitt M. B. , Cromwell J. W. , Byrn J. C.
Published: October 2014

Aim

Conversion rates from laparoscopic to open colectomy and associated factors are traditionally reported in clinical trials or reviews of outcomes from experienced institutions. Indications and selection criteria for laparoscopic colectomy may be more narrowly defined in these circumstances. With the increased adoption of laparoscopy, conversion rates using national data need to be closely examined. The purpose of this study was to use data from the American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP) to identify factors associated with conversion of laparoscopic to open colectomy at a national scale in the United States.

Method

The ACS‐NSQIP Participant Use Data Files for 2006–2011 were used to identify patients who had undergone laparoscopic colectomy. Converted cases were identified using open colectomy as the primary procedure and laparoscopic colectomy as ‘other procedure’. Preoperative variables were identified and statistics were calculated using sas version 9.3. Logistic regression was used to model the multivariate relationship between patient variables and conversion status.

Results

Laparoscopy was successfully performed in 41 585 patients, of whom 2508 (5.8%) required conversion to an open procedure. On univariate analysis the following factors were significant: age, body mass index (BMI), American Society of Anesthesiologists (ASA) class, presence of diabetes, smoking, chronic obstructive pulmonary disease, ascites, stroke, weight loss and chemotherapy (P < 0.05). The following factors remained significant on multivariate analysis: age, BMI, ASA class, smoking, ascites and weight loss.

Conclusion

Multiple significant factors for conversion from laparoscopic to open colectomy were identified. A novel finding was the increased risk of conversion for underweight patients. As laparoscopic colectomy is become increasingly utilized, factors predictive of conversion to open procedures should be sought via large national cohorts.
Histopathological evaluation of the effects of variable extraoral dry times and enamel matrix proteins (enamel matrix derivatives) application on replanted dogs' teeth
Authors: Barbizam Joao V. B. , Massarwa Rasha , da Silva Lea Assed Bezerra , da Silva Raquel Assed Bezerra , Nelson‐Filho Paulo , Consolaro Alberto , Cohenca Nestor
Published: October 2014

The extra‐alveolar dry period and storage medium in which the tooth was kept prior to replantation remain the critical factors affecting the survival and regeneration of the damaged periodontium. When the replantation is delayed, replacement root resorption is the most common complication following replantation of an avulsed tooth. The aim of this histological study was to evaluate the periodontal healing of replanted dogs' teeth after 20 min (short) and 60 min (long) extraoral dry time with and without the application of enamel matrix proteins. Eighty mature premolar roots (40 teeth) maxillary and mandibular premolars were extracted, the root canals were accessed, instrumented, and filled using a lateral condensation technique, and the access cavity was restored with amalgam. Each root was randomly assigned to one of experimental groups: Groups I and II: Roots were replanted after an extraoral dry time of 20 min. In group II, Emdogain® (Biora, Malmo, Sweden) was applied directly to the external root surface with complete coverage. Groups III and IV: Roots were replanted after an extraoral dry time of 60 min. In group IV, Emdogain® was applied to the whole external root surface before replantation. Roots that replanted within a total extraoral dry time of 10 min were used as negative controls, while those replanted after 90 min of extraoral dry time were assigned as positive controls. After 4 months, the dogs were euthanized, and the maxillary and mandibular processes were processed for histology and microscopically evaluated. Statistical analysis showed no significant differences (P = 0.1075) among the experimental groups. The results of this study show that 20 min of extraoral dry time is as detrimental to the PDL cells as 60 or 90 min of extraoral dry time, with avulsed dogs' teeth, even when replanted with an inductive material such as EMD. This study provides strong evidence in relation to the threshold of the extraoral dry time of avulsed teeth, suggesting that the extraoral dry time threshold of PDL cell viability is significantly less than that which current guidelines promote.
Behaviour and biology ofChilo partelluson maize landraces
Authors: Mutyambai Daniel M. , Midega Charles A.O. , Bruce Toby J.A. , van den Berg Johnnie , Pickett John A. , Khan Zeyaur R.
Published: October 2014

Plants defend themselves against herbivores through activation of both constitutive and induced defences. Previous studies reported that egg deposition on maize landraces induces the release of volatiles that attract parasitoids, but little is known on the effect of these volatiles on subsequent herbivore oviposition. In addition, larval preference and development on these maize landraces is unknown. We evaluated six landraces and one hybrid maize variety for their resistance toChilo partellus(Swinhoe) (Lepidoptera:Crambidae). Larval orientation, settling, arrest and dispersal, feeding, development, survival, and subsequent oviposition of moths were determined for individuals reared on each of these varieties under laboratory and screen house conditions. For oviposition preference studies, all treatments were initially exposed to egg deposition whereas the control treatments were not. Larval preference was generally higher for hybrid maize, compared to the landraces. Similarly, first‐instar feeding on maize leaves was more intense in hybrid maize than in four of the six landraces. The amount of food consumed and assimilated by third instars over a 24‐h period was, however, not different among the maize varieties. Larval survival was significantly lower in maize landraces (32%) compared to hybrid maize (54%). However, there was no difference in the larval development period between any of the treatments. Two‐choice oviposition assays showed that moths preferred non‐exposed maize landraces for subsequent oviposition, whereas in the hybrid, there was no difference in oviposition preference between exposed and non‐exposed plants. Although the mechanism of larval suppression was beyond the scope of this study, it was inferred that the landraces showed some resistance toC. partellusfeeding and that initial egg deposition on these landraces deters further colonisation by the herbivore.
Microbial degradation of organic carbon sorbed to phyllosilicate clays with and without hydrous iron oxide coating
Authors: Saidy A. R. , Smernik R. J. , Baldock J. A. , Kaiser K. , Sanderman J.
Published: October 2014

Sorption of organic carbon (OC) to phyllosilicate clays and hydrous iron oxides retards its mineralization, thus contributing to stabilization of organic carbon in soils. The degree of protection varies with the nature of the minerals present. In a previous study, we reported that when the amount of OC exceeds the sorption capacity of minerals, the rate of OC mineralization is determined primarily by mineral surface area. Here, we report on OC mineralization under conditions of less OC loading and with OC pre‐sorbed to the mineral surfaces. The same suite of minerals (kaolinite, illite and smectite with and without goethite coating and illite coated with haematite, goethite and ferrihydrite) was used as in the previous study. The stability of sorbed OC decreased in the order kaolinite > illite > smectite amongst the uncoated clays. Goethite coating of kaolinite and smectite increased the stability of sorbed OM against microbial decomposition, while the stability of illite‐associated OC did not change with goethite coating. For illite coated with different hydrous iron oxides, only ferrihydrite increased the stability of sorbed OC against microbial decomposition. These differences reflect closely the differences in the strength and reversibility of OC sorption, as measured in previous batch sorption experiments on these systems, rather than reflecting differences in mineral surface area. These findings demonstrate that at relatively small loadings of OC, the degree of protection of sorbed OC provided by mineral surfaces is controlled primarily by the strength of organo–mineral associations.
The Internationalisation of Regions: Paradiplomacy or Multi‐level Governance?
Authors: Dickson Francesca
Published: October 2014

This article reviews the two primary frameworks used to explore the external relations of regions. It argues that the concepts of multi‐level governance and paradiplomacy are used to describe similar, but distinct, international activities on the part of regions and sub‐state governments. Both approaches look at the ways in which regions engage beyond the local level, and increasingly so. The inevitable overlap between their subject matter has meant that the two terms are sometimes used interchangeably, leading to a mischaracterisation of the practices themselves. The international mobilisation of regions manifests in numerous modes, and therefore much greater specificity is required in analysing and interpreting these varied phenomena. In particular, the novelty of paradiplomacy, and the political contestation that it can imply, risks being under‐reported. Firmer boundaries between the two approaches, and a better conceptualisation of the relationship between them, are called for in this interdisciplinary review. The article argues that where multi‐level governance presents a predominately structural account of ‘governance’ based activities, paradiplomacy has the potential to provide an agency‐oriented explanation of autonomous, diplomatic practices – often with deeply political connotations. It is suggested that the two can represent parallel, alternative or complementary approaches, depending on the exact nature of the activity under consideration. It concludes by suggesting future avenues for paradiplomatic research.
Geographical Studies of Humor
Authors: Ridanpää Juha
Published: October 2014

Humor is a spatially embedded institution in many ways. Although a highly marginal field of study, the number of geographical studies on humor has been increasing lately. The aim of this article is to introduce the various approaches and also draw connecting links between them. The review shows how practices of popular media are geopolitically charged, how humor is intertwined with issues of social marginalization, how humor operates as an important element in the construction of group cohesion, how humor works as a non‐cognitive element of human actions, feelings, and emotions, as well as how it represents a useful tool for educational and economic purposes, and how all of this has been studied by scholars of geography. The review shows the various directions of the geographical studies of humor at the same time emphasizing that the relevance, variety, and multidimensionality of the topic have not been fully recognized.
Cultural Ecosystem Services and the Challenge for Cultural Geography
Authors: Leyshon Catherine
Published: October 2014

Cultural ecosystem services are one of four services identified by the Millennium Ecosystem Assessment as critical to the support of human life on earth and therefore in need of proper valuation and protection. Cultural services seem to embody the objects of enquiry for cultural geographers interested in landscape, identity and place. However, potentially insurmountable epistemological challenges face the participation of cultural geographers in the following: (i) the identification and evaluation of CES; and (ii) the operationalisation of environmental governance. One challenge for cultural geographers is to make the relevance of their theoretical and conceptual insights felt in a field dominated by the natural sciences and scientific epistemologies. Meanwhile, the problems of defining and identifying cultural services in ways that make them compatible with provision, regulating and supporting services, even threaten the continued inclusion of cultural services in the ecosystem services approach. The concept of landscape seems to provide a shared intellectual terrain over which cultural geographers can work with others interested in cultural ecosystem services.
For Geographies of Children, Young People and Popular Culture
Authors: Horton John
Published: October 2014

This paper calls for more direct, careful, sustained research on geographies of children, young people and popular culture. I present three sets of empirical and conceptual resources for researchers developing work in this area. Part 1 signposts classic work from cultural/media studies, marketing and sociology, which has been centrally concerned with meanings of popular culture designed for children and young people (e.g. via critiques of the gendered content of iconic popular cultural phenomena). Part 2 foregrounds nascent conceptualisations of social‐material geographies of childhood and youth. I argue that these conceptualisations can extend and unsettle classic work on popular culture, by questioning how popular cultural texts, objects and phenomena matter. Halfway through the paper is a ‘commercial break’. Here, I present some personal reflections on working at the intersection between the ideas discussed in Parts 1 and 2. With reference to a specific popular cultural artefact (the Toys ‘Я’ Us Christmas toy catalogue), I argue that both meanings and matterings are crucial for geographers engaging with children and young people's popular cultures. In conclusion, I argue that more geographers should engage with the literature and issues outlined in Part 1, but also that the geographical concepts discussed in Part 2 demand new modes of research, thinking and writing in relation to popular cultural texts, objects and phenomena.
Dementia in patients with atrial fibrillation and the value of the Hachinski ischemic score
Authors: Di Nisio Marcello , Prisciandaro Michele , Rutjes Anne WS , Russi Ilaria , Maiorini Luisa , Porreca Ettore
Published: October 2014

Aim

To assess the prevalence of vascular dementia, mixed dementia and Alzheimer's disease in patients with atrial fibrillation, and to evaluate the accuracy of the Hachinski ischemic score for these subtypes of dementia.

Methods

A nested case–control study was carried out. A total of 103 of 784 consecutive patients evaluated for cognitive status at the Ambulatory Geriatric Clinic had a diagnosis of atrial fibrillation. Controls without atrial fibrillation were randomly selected from the remaining 681 patients using a 1:2 matching for sex, age and education.

Results

The prevalence of vascular dementia was twofold in patients with atrial fibrillation compared with controls (21.4% vs 10.7%, P = 0.024). Alzheimer's disease was also more frequent in the group with atrial fibrillation (12.6% vs 7.3%, P = 0.046), whereas mixed dementia had a similar distribution. The Hachinski ischemic score poorly discriminated between dementia subtypes, with misclassification rates between 46% (95% CI 28–66) and 70% (95% CI 55–83). In patients with atrial fibrillation, these rates ranged from 55% (95% CI 32–77) to 69% (95% CI 39–91%). In patients in whom the diagnosis of dementia was excluded, the Hachinski ischemic score suggested the presence of vascular dementia in 11% and mixed dementia in 30%.

Conclusions

Vascular dementia and Alzheimer's disease, but not mixed dementia, are more prevalent in patients with atrial fibrillation. The discriminative accuracy of the Hachinski ischemic score for dementia subtypes in atrial fibrillation is poor, with a significant proportion of misclassifications. Geriatr Gerontol Int 2015; 15: 770–777.
Correlation between dispensed and prescribed doses of factor products for bleeding disorders: can a small, centre‐based pharmacy hit the mark?
Authors: Croteau S. E. , Saxena K. , Neufeld E. J.
Published: October 2014

The prescribing and dispensing of factor replacement products have come under scrutiny in recent years. Some payers are shunting patients away from local 340B pharmacies anticipating larger pharmacies will be better able to match dispensed antihaemophilic factor vials to the prescribed dose. Our aims were to assess our baseline ability to achieve an aggregate and per patient dispensed to prescribed factor ratio (D:P ratio) of 1 and to evaluate obstacles to achieving unity. We conducted a retrospective review of the factor products dispensed from our 340B pharmacy and the corresponding prescriptions over the 6‐month period prior to instituting routine D:P ratio assessment. The mean D:P ratio for all 65 patients was 1.00 (SD = 0.07). The mean paediatric D:P ratio differed from unity (P = 0.017) and from the mean adult D:P ratio (P = 0.003) in favour of a higher dispensed dose. A correlation between lighter patients and a higher dispensed dose was observed. Also, paediatric patients receiving 2 vials per dose had a mean D:P ratio greater than unity (P = 0.002). Pharmacy size does not dictate the ability to achieve a D:P ratio of unity. Ongoing monitoring of D:P ratios and dose ranges prescribed should be performed by all pharmacies to ensure acceptable allocation and cost of factor replacement for each patient. To further improve the D:P ratio metric in the paediatric population manufacturers should strongly consider adding more nominal dose increments within their lower range of vial sizes.
Different effect of oral cyclosporine therapy and oral antihistamine therapy on serum high‐sensitivity C‐reactive protein level and thymus and activation‐regulated chemokine level in atopic dermatitis in older children and adulthood
Authors: Ohtsuka Tsutomu
Published: October 2014

Background

Many patients with atopic dermatitis (AD) are treated with oral cyclosporine or antihistamine therapy in clinical practice.

Objective

To evaluate the effectiveness of oral cyclosporine and antihistamine therapy on clinical and laboratory findings in patients with AD.

Subjects and methods

Twenty‐five patients with AD (male–female = 11 : 14, age 16–42 years old, mean 26.2 years old) were treated with oral cyclosporine therapy. Twenty‐three patients with AD (male–female = 10 : 13, age 15–32 years old, mean 24.2 years old) were treated with oral antihistamine therapy. Laboratory findings including high‐sensitivity C‐reactive protein (CRP) and thymus and activation‐regulated chemokine (TARC) were statistically studied.

Results

Serum TARC level after oral cyclosporine therapy (1013 ± 883 pg/ml) was significantly decreased compared to before therapy (38 194 ± 4678 pg/ml; P < 0.02). Basophil counts in peripheral blood after the therapy (49.7 ± 26.4 × 10−3 cells/μl) were more significantly increased than before therapy (41.1 ± 16.7 × 10−3 cells/μl; P < 0.05). Serum high‐sensitivity CRP level after antihistamine therapy (0.09 ± 0.08 mg/ml) was significantly decreased compared to before therapy (0.13 ± 0.12 mg/ml; P < 0.05). Basophil counts in peripheral blood after the therapy (33.4 ± 16.2 × 10−3 cells/μl) were more significantly decreased than before therapy (41.5 ± 23.3 × 10−3 cells/μl; P < 0.01).

Conclusion

Different effects of oral cyclosporine therapy and oral antihistamine therapy to serum high‐sensitivity CRP level, TARC level, and peripheral blood basophils in adult patients with AD were shown. A combination of these two therapies may be more effective for the treatment of AD in adults.
Bench to bedside: mechanistic principles of targeting the RAF kinase in melanoma
Authors: Rajakulendran Thanashan , Adam David N.
Published: October 2014

Melanoma, in its advanced form, is an aggressive cancer with a poor prognosis. To date, no therapeutic modality has afforded a high likelihood of curative outcome, with the exception of early surgical resection in patients diagnosed with local disease. However, recent advances in our understanding of the molecular mechanisms and pathophysiology of melanoma have paved the way towards the development of targeted therapeutics. A central player in melanomagenesis is the RAF family of kinases. Key mechanistic details regarding the regulation of RAF kinases have now begun to emerge. Already, vemurafenib, a tailored kinase inhibitor of aberrant RAF function in melanoma, has led to clinical benefit. Despite vemurafenib's success, acquired resistance to the drug warrants the need for further drug development. In this review, we discuss the critical role of RAF dimerization in both melanomagenesis and resistance to RAF inhibitors such as vemurafenib. We also highlight the potential for inhibitors of RAF dimerization to lead to improved outcomes in patients with advanced melanoma.
Finding Bayesian Optimal Designs for Nonlinear Models: A Semidefinite Programming‐Based Approach
Authors: Duarte Belmiro P. M. , Wong Weng Kee
Published: October 2014

This paper uses semidefinite programming (SDP) to construct Bayesian optimal design for nonlinear regression models. The setup here extends the formulation of the optimal designs problem as an SDP problem from linear to nonlinear models. Gaussian quadrature formulas (GQF) are used to compute the expectation in the Bayesian design criterion, such as D‐, A‐ or E‐optimality. As an illustrative example, we demonstrate the approach using the power‐logistic model and compare results in the literature. Additionally, we investigate how the optimal design is impacted by different discretising schemes for the design space, different amounts of uncertainty in the parameter values, different choices of GQF and different prior distributions for the vector of model parameters, including normal priors with and without correlated components. Further applications to find Bayesian D‐optimal designs with two regressors for a logistic model and a two‐variable generalised linear model with a gamma distributed response are discussed, and some limitations of our approach are noted.
Dual‐color, break‐apart fluorescence in situ hybridization probe for distinguishing clear cell sarcoma of soft tissue from malignant melanoma
Authors: Yoon Jung Hee , Baek Yoo Sang , Jeon Jiehyun , Oh Chil Hwan , Song Hae Jun
Published: October 2014

Background Clear cell sarcoma (CCS) of soft tissue is a rare soft tissue sarcoma with melanocytic differentiation and shares morphologic, immunohistochemical, ultrastructural, and molecular features with malignant melanoma (MM). Because the prognosis of CCS is much different from MM, it is important to distinguish each other by selective method. CCS is well‐recognized as having the t(12;22)(q13;q12) translocation, on the other hand MM is not. Therefore, detecting Ewing sarcoma region 1 (ESWR1) gene rearrangement can serve as a crucial diagnostic determinant.

Methods Biopsy was taken from a 52‐year‐old man who reported a 3‐year history of a gradually enlarging nodule on the sole of his left foot. Routine and special stains for melanocytic markers and fluorescence in situ hybridization (FISH) evaluation using dual color break‐apart rearrangement probes specific for ESWR1 was performed for formalin‐fixed tissue.

Results Neoplastic cells expressed diffuse but strong positivity for HMB45 and S100 but not for Melan‐A. Dual color, break‐apart interphase FISH revealed EWS(22q12) gene rearrangements in CCS tumor cells.

Conclusion Fluorescence in situ hybridization evaluation using ESWR1 gene probe for CCS sharing clinical and histopathological characteristics with MM is a valuable tool to distinguish each other.
Orchestrating the XO computer with digital and conventional resources to teach mathematics
Authors: Díaz A. , Nussbaum M. , Varela I.
Published: October 2014

Recent research has suggested that simply providing each child with a computer does not lead to an improvement in learning. Given that dozens of countries across the world are purchasing computers for their students, we ask which elements are necessary to improve learning when introducing digital resources into the classroom. Understood the orchestration as the coordination of conventional and digital resources, we examine whether effective resource orchestration improves student learning. To do so, an 8‐month study was undertaken across 17 schools in Uruguay, involving 544 fourth grade students. A treatment group worked under an orchestrated strategy, while a control group followed the national strategy, which includes the One Laptop per Child Computer (XO). Our study confirmed that the national strategy alone is capable of producing significant progress in student learning. However, we also found that the orchestration produces a statistically significant improvement in the results when compared to the control group. The main finding indicates that when teachers have an orchestrated strategy to integrate digital and non‐digital resources, student learning is enhanced in relation to the curricular objectives. Finally, we discovered that learning is improved in the treatment group when there is systematic use of resources, and when the school's infrastructure facilitates the use of the technology.
Post‐translational modifications of transthyretin affect the triiodonine‐binding potential
Authors: Henze Andrea , Homann Thomas , Serteser Mustafa , Can Ozge , Sezgin Ozlem , Coskun Abdurrahman , Unsal Ibrahim , Schweigert Florian J. , Ozpinar Aysel
Published: October 2014

Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10), which is frequently affected by oxidative post‐translational modifications. As Cys10 is part of the thyroid hormone‐binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype‐ and site‐specific manner with S‐glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function‐specific patterns of TTR with a substantial decrease in S‐sulphonated, S‐cysteinylglycinated and S‐glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability.
Comparing High‐throughput Platforms for Sequencing the V4 Region of SSU‐rDNA in Environmental Microbial Eukaryotic Diversity Surveys
Authors: Mahé Frédéric , Mayor Jordan , Bunge John , Chi Jingyun , Siemensmeyer Tobias , Stoeck Thorsten , Wahl Benjamin , Paprotka Tobias , Filker Sabine , Dunthorn Micah
Published: October 2014

High‐throughput sequencing platforms are continuing to increase resulting read lengths, which is allowing for a deeper and more accurate depiction of environmental microbial diversity. With the nascent Reagent Kit v3, Illumina MiSeq now has the ability to sequence the eukaryotic hyper‐variable V4 region of the SSU‐rDNA locus with paired‐end reads. Using DNA collected from soils with analyses of strictly‐ and nearly identical amplicons, here we ask how the new Illumina MiSeq data compares with what we can obtain with Roche/454 GS FLX with regard to quantity and quality, presence and absence, and abundance perspectives. We show that there is an easy qualitative transition from the Roche/454 to the Illumina MiSeq platforms. The ease of this transition is more nuanced quantitatively for low‐abundant amplicons, although estimates of abundances are known to also vary within platforms.