bluuebunny/crossref_metadata_2025 huggingface dataset:
The genealogical analysis of the HKSAR’s civic education policy
Authors: Chung Fun Steven Hung
Published: April 2015

Purpose

– Civic education in Hong Kong is quite confusing nowadays. To understand the policy, it should be placed into the reality of its historical context. In addition, to read through the documentary presentation of policy, the policy’s proposal and its initiation should be understood with an understanding of contextual progress and historical change following the handover of sovereignty to China. The paper aims to discuss these issues.

Design/methodology/approach

– The genealogical knowledge of policy history is applied for the purpose of understanding civic education. The concepts of genealogy put forward present an anti-essentialist position and are opposed to focusing on a singular or dominant ideology.

Findings

– As the government-dominated power, any knowledge of civic education was bound to be nationally identified and patriotic for the purposes of strengthening nation-state awareness. Another approach of moral education was adopted that emphasized traditional Chinese cultures and values in order to cultivate a recognition of a harmonious society in students.

Originality/value

– The paper helps to analyse the government-dominated process of knowledge formation in a value setting.
Coexistence of pemphigus foliaceus and acquired hemophilia A: A case report
Authors: Filipczak Aleksandra , Michalska‐Jakubus Małgorzata , Górska‐Kosicka Magdalena , Woźniak Katarzyna , Kowalewski Cezary , Krupski Witold , Pietrzak Aldona , Wallner Grzegorz , Mosiewicz Jerzy , Lotti Torello , Krasowska Dorota
Published: April 2015

Pemphigus foliaceus (PF) is an autoimmune bullous dermatosis with anti‐desmoglein‐1 autoantibodies. Acquired hemophilia A (AHA) is a rare coagulation disorder with a high mortality rate, caused by anti‐factor VIII immunoglobulin G antibodies leading to spontaneous severe hemorrhages into skin, muscles or soft tissues. This coagulopathy may be associated with malignancies, drug reactions and autoimmune disorders including bullous dermatoses. Herein, we demonstrate a first report of AHA in the course of pemphigus foliaceus. A 55‐year‐old woman presenting with extensive, erosive, crusted, scaly skin lesions was diagnosed with PF based on histopathological and immunofluorescent examination, confirmed by the presence of anti‐desmoglein‐1 antibodies on enzyme‐linked immunoassay. She developed extensive internal hemorrhages and prolonged external bleeding after laparotomy. Based on coagulation tests, AHA was diagnosed. Simultaneous remission of pemphigus and coagulopathy occurred with immunosuppressants and recombinant activated factor VII.
Geomechanical property estimation of unconventional reservoirs using seismic data and rock physics
Authors: Glinsky Michael E. , Cortis Andrea , Chen Jinsong , Sassen Doug , Rael Howard
Published: April 2015

An extension of a previously developed rock physics model is made that quantifies the relationship between the ductile fraction of a brittle/ductile binary mixture and the isotropic seismic reflection response. By making a weak scattering (Born) approximation and plane wave (eikonal) approximation, with a subsequent ordering according to the angles of incidence, singular value decomposition analyses are performed to understand the stack weightings, number of stacks, and the type of stacks that will optimally estimate two fundamental rock physics parameters – the ductile fraction and the compaction and/or diagenesis. It is concluded that the full PP stack, i.e., sum of all PP offset traces, and the “full” PS stack, i.e., linear weighted sum of PS offset traces, are the two optimal stacks needed to estimate the two rock physics parameters. They dominate over both the second‐order amplitude variation offset “gradient” stack, which is a quadratically weighted sum of PP offset traces that is effectively the far offset traces minus the near offset traces, and the higher order fourth order PP stack (even at large angles of incidence). Using this result and model‐based Bayesian inversion, the seismic detectability of the ductile fraction (shown by others to be the important rock property for the geomechanical response of unconventional reservoir fracking) is demonstrated on a model characteristic of the Marcellus shale play.
Role of Peptide YY in blood vessel function and atherosclerosis in a rabbit model
Authors: Smith Renee M , Klein Rudi , Kruzliak Peter , Zulli Anthony
Published: April 2015

Cardiovascular disease remains a burden for Westernized countries. Peptide YY (PYY) raises blood pressure, yet its role has not yet been determined in diseased arteries. This study aimed at identifying PYY and eNOS in diseased blood vessels and to determine which blood vessels respond to PYY. New Zealand White rabbits were fed an atherogenic diet (n = 6, 0.5% cholesterol + 1% methionine + 5% peanut oil) and control animals fed a normal diet (n = 6) for 4 weeks. Immunohistochemistry was used to determine the localization of PYY and eNOS in the aorta. The aorta, carotid, renal, iliac, inferior mesenteric, and renal interlobular arteries were removed, mounted in organ baths, and subjected to doses of PYY (10−9–10−7 mol/L) and then acetylcholine (10−6 mol/L). Immunohistochemistry of the aorta shows PYY staining in plaque macrophages, smooth muscle cells and endothelium, and these cells co‐expressed eNOS. PYY caused a minor vasoconstrictive response in all blood vessels studied but was blunted in arteries from control animals. Acetylcholine caused relaxation of PYY constricted blood vessels. This data clearly shows that PYY is present in atherosclerotic plaque and is a minor constrictor of the vasculature tree. Further studies aimed at understanding the role of PYY in cardiovascular disease are warranted.
Can oral vitamin D prevent the cardiovascular diseases among migrants in Australia? Provider perspective using Markov modelling
Authors: Ruwanpathirana Thilanga , Owen Alice , Renzaho Andre MN , Zomer Ella , Gambhir Manoj , Reid Christopher M
Published: April 2015

The study was designed to model the effectiveness and cost effectiveness of oral Vitamin D supplementation as a primary prevention strategy for cardiovascular disease among a migrant population in Australia. It was carried out in the Community Health Service, Kensington, Melbourne. Best‐case scenario analysis using a Markov model was employed to look at the health care providers’ perspective. Adult migrants who were vitamin D deficient and free from cardiovascular disease visiting the medical centre at least once during the period from 1 January 2010 to 31 December 2012 were included in the study. The blood pressure‐lowering effect of vitamin D was taken from a published meta‐analysis and applied in the Framingham 10 year cardiovascular risk algorithm (with and without oral vitamin D supplements) to generate the probabilities of cardiovascular events. A Markov decision model was used to estimate the provider costs associated with the events and treatments. Uncertainties were derived by Monte Carlo simulation. Vitamin D oral supplementation (1000 IU/day) for 10 years could potentially prevent 31 (interquartile range (IQR) 26 to 37) non‐fatal and 11 (IQR 10 to 15) fatal cardiovascular events in a migrant population of 10 000 assuming 100% compliance. The provider perspective incremental cost effectiveness per year of life saved was AU$3,992 (IQR 583 to 8558). This study suggests subsidised supplementation of oral vitamin D may be a cost effective intervention to reduce non‐fatal and fatal cardiovascular outcomes in high‐risk migrant populations.
Too Big to Learn: The Effects of Major Acquisition Failures on Subsequent Acquisition Divestment
Authors: Meschi Pierre‐Xavier , Métais Emmanuel
Published: April 2015

We examine whether firms learn from their major acquisition failures. Drawing from a threat‐rigidity theoretical framework, we suggest that firms do not learn from their major acquisition failures. Furthermore, we hypothesize that host‐country experience reinforces the negative effects of major acquisition failures. Our research hypotheses are tested using an event history analysis of 741 acquisitions undertaken by French listed and non‐listed firms in the USA between January 1988 and December 2008. We use failure divestment (divestment resulting from acquisition failure) as a proxy for acquisition performance. Consistent with our theoretical framework, we find that major acquisition failures have a negative impact on future acquisition performance. Furthermore, we find that such negative effects are reinforced by firms’ host‐country experience.
Loss of heterozygosity at the human leukocyte antigen locus in thymic epithelial tumors
Authors: Chen Yuan , Wang Guojin , Zhang Peng , Liu Yimei , Yao Yuanyuan , Wang Hai , Wang Yuanguo
Published: April 2015

Background

To study the relationship between loss of heterozygosity (LOH) at the human leukocyte antigen (HLA) locus and the pathogenicity and clinicopathological features of thymic epithelial tumors (TET).

Methods

Tumor and adjacent normal tissues were isolated from 36 TET patients. Five microsatellite loci (D6S1666, D6S265, D6S273, DS6276, and D6S291) within the HLA locus were amplified by polymerase chain reaction. DNA sequencing was used to measure the frequency of microsatellite LOH.

Results

LOH was identified in at least one locus in 83.6% of TET patients. LOH frequency at D6S1666, D6S265, D6S273, D6S276, and D6S291 was 44.4%, 16.7%, 30.5%, 38.9%, and 36.1% respectively. There was no significant association between LOH frequency in TET with tumor severity, or in the presence or absence of myasthenia gravis.

Conclusions

D6S1666, D6S265, D6S273, DS6S276, and D6S29 are sensitive loci for studying microsatellite LOH in TET. LOH within the HLA complex is implicated in the occurrence and development of TET, with the HLA‐DQA1 gene likely involved. However, an understanding of the relationship between LOH and the clinicopathological features of TET requires a larger sample size than that of the present study.
Trapped Cash and the Profitability of Foreign Acquisitions
Authors: Edwards Alexander , Kravet Todd , Wilson Ryan
Published: April 2015

Current U.S. reporting and tax laws create an incentive for some U.S. firms to avoid the repatriation of foreign earnings, as the U.S. government charges additional corporate taxes on these transfers. Prior research suggests that the combined effect of these incentives leads some U.S. multinational corporations to hold a significant amount of cash overseas. In this study, we investigate the effect of cash trapped overseas on U.S. multinational corporations' foreign acquisitions. Consistent with expectations, we observe firms with high levels of trapped cash make less profitable acquisitions of foreign target firms using cash consideration (lower announcement window returns, lower buy and hold returns, decreased ROA). The American Jobs Creation Act of 2004 (AJCA) reduced this effect by allowing firms to repatriate foreign earnings held as cash abroad at a much lower tax cost. Our study has implications for current proposals to change the tax laws related to foreign earnings.
Efficacy and safety of electroconvulsive therapy in the first trimester of pregnancy: a case of severe manic catatonia
Authors: Pinna Martina , Manchia Mirko , Pillai Gianluca , Salis Piergiorgio , Minnai Gian Paolo
Published: April 2015

Objectives

Electroconvulsive therapy (ECT) is an appropriate, albeit often neglected, option for managing severe or life‐threatening psychiatric symptoms during pregnancy. We report on the rapid effectiveness and safety of ECT during the first trimester of pregnancy in a 28‐year‐old woman with severe catatonia.

Methods

Catatonic symptoms were assessed using the Catatonia Rating Scale (CRS). The patient was treated with unilateral ECT using left anterior right temporal (LART) placement. Seizure quality and duration were monitored by a two‐lead electroencephalograph (EEG) and by one‐lead electromyography (EMG). During each ECT session, the fetal heart rate was monitored with electrocardiogram (ECG).

Results

After the second ECT treatment (day 13 of hospitalization), we observed remission of the catatonic symptoms, as shown by the drop in the CRS score from 22 to 0. No cognitive abnormalities were reported and no gynecological complications were detected (e.g. vaginal bleeding, abdominal pain, or uterine contraction). The patient delivered at term a healthy male neonate who presented normal growth as well as normal psychomotor development.

Conclusions

This case highlights the effectiveness of ECT in treating severe catatonic mania during the first 3 months of pregnancy. In addition, ECT proved to be a safe therapeutic option, since neither mother nor infant experienced any adverse event. We suggest that ECT might be considered as a valid and safe option in the therapeutic decision‐making process when catatonic symptoms manifest during pregnancy.
Outcomes in splenic marginal zone lymphoma: analysis of 107 patients treated in British Columbia
Authors: Xing Katharine H. , Kahlon Amrit , Skinnider Brian F. , Connors Joseph M. , Gascoyne Randy D. , Sehn Laurie H. , Savage Kerry J. , Slack Graham W. , Shenkier Tamara N. , Klasa Richard , Gerrie Alina S. , Villa Diego
Published: April 2015

Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non‐Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30–88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10‐year overall survival for first‐line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26–0·88, P = 0·017]. The 10‐year failure‐free survival (FFS) after first‐line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28–0·80, P = 0·004). Among the 38 patients who received first‐line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31–1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10‐year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL.
Tree Species Richness Strengthens Relationships between Ants and the Functional Composition of Spider Assemblages in a Highly Diverse Forest
Authors: Schuldt Andreas , Staab Michael
Published: April 2015

In species‐rich ecosystems, such as subtropical and tropical forests, higher trophic level interactions are key mediators of ecosystem functioning. Plant species loss may alter these interactions, but the effects of plant diversity might be modified by intraguild interactions, particularly among predators. We analyzed the relationships between spiders and ants, two dominant predatory arthropod taxa, on tree saplings across a gradient from medium to high woody plant species richness in a subtropical forest in Southeast China. Neither ant nor spider total biomass was significantly related to plant species richness. By contrast, the biomass distribution of web‐building and hunting spiders changed and spider family richness increased in the presence of ants, resulting in more web builder‐dominated assemblages. However, these relationships depended on the plant communities, and were stronger in plots with higher plant species richness. Our results indicate that in addition to potential effects of ants on hunting spiders in particular, ants could indirectly influence intraguild interactions within spider assemblages. The observed shifts in the spider assemblages with increasing ant presence and plant species richness may have functional consequences, as web‐building and hunting spiders have distinct prey spectra. The relationships among ants, spiders, and plant species richness might contribute to explaining the non‐significant relationship between the overall effects of predators and plant diversity previously observed in the same forest plots. Our findings thus give insight into the complexity of biotic interactions in such species‐rich ecosystems.
Density‐dependent Survival in Seedlings Differs among Woody Life‐forms in Tropical Wet Forests of a Caribbean Island
Authors: DeWalt Saara J. , Taylor Benton N. , Ickes Kalan
Published: April 2015

Negative density dependence contributes to seedling dynamics in forested ecosystems, but the relative importance of this factor for different woody plant life‐forms is not well‐understood. We used 1 yr of seedling survivorship data for woody seedlings in 17 different plots of lower to mid‐montane rain forests on the island of Dominica to examine how seedling height, abiotic factors, and biotic factors such as negative density dependence are related to seedling survival of five different life‐forms (canopy, midstory, and understory trees; shrubs; and lianas). Across 64 species, taller seedlings in seedling plots with higher canopy openness, greater seedling density, lower relative abundance of conspecific seedlings, and lower relative abundance of conspecific adults generally had a greater probability of surviving. Height was the strongest predictor of seedling survival for all life‐forms except lianas. Greater seedling density was positively related to survival for canopy and midstory trees but negatively related to survival for the other life‐forms. For trees, the relative abundance of conspecific seedling and adult neighbors had weak and strong negative effects on survival respectively. Neither shrub nor liana seedling survival was affected by the relative abundance of conspecific neighbors. Thus, negative density dependence is confirmed as an important structuring mechanism for tree seedling communities but does not seem to be important for lianas and shrubs in Dominican rain forests. These results represent the first direct assessment of controls on seedling survival of all woody life‐forms – an important step in understanding the dynamics and structure of the entire woody plant community.
Age‐related Crown Thinning in Tropical Forest Trees
Authors: Quinn Eadaoin M. , Thomas Sean C.
Published: April 2015

Gap dynamics theory proposes that treefall gaps provide high light levels needed for regeneration in the understory, and by increasing heterogeneity in the light environment allow light‐demanding tree species to persist in the community. Recent studies have demonstrated age‐related declines in leaf area index of individual temperate trees, highlighting a mechanism for gradual changes in the forest canopy that may also be an important, but less obvious, driver of forest dynamics. We assessed the prevalence of age‐related crown thinning among 12 tropical canopy tree species sampled in lowland forests in Panama and Puerto Rico (total N = 881). Canopy gap fraction of individual canopy tree crowns was positively related to stem diameter at 1.3 m (diameter at breast height) in a pooled analysis, with 10 of 12 species showing a positive trend. Considered individually, a positive correlation between stem diameter and canopy gap fraction was statistically significant in 4 of 12 species, all of which were large‐statured canopy to emergent species: Beilschmiedia pendula, Ceiba pentandra, Jacaranda copaia, and Prioria copaifera. Pooled analyses also showed a negative relationship between liana abundance and canopy gap fraction, suggesting that lianas could be partially obscuring age‐related crown thinning. We conclude that age‐related crown thinning occurs in tropical forests, and could thus influence patterns of tree regeneration and tropical forest community dynamics.
Emerging Sensitivity to Socially Complex Expressions: A Unique Role for Adolescence?
Authors: Garcia Natalie V. , Scherf K. Suzanne
Published: April 2015

Complex facial expressions provide signals about emotions that are related to nuanced social behavior (e.g., shame, desire) and inner thoughts (e.g., pensive). In this article, we review the empirical evidence evaluating whether the ability to recognize these complex expressions changes during adolescence, given the increasing evidence of heightened sensitivity to social signals during this time. We propose considerations for interpreting findings from this work and shaping research. Finally, we offer a new hypothesis about the influences of age and pubertal maturation on the development of processing complex facial expressions during adolescence, and propose that puberty influences the emergence of sensitivity to particular kinds of complex expressions, namely social sexual expressions. This hypothesis is embedded in a broader theory about how age‐appropriate social developmental tasks, like forming loyal peer friendships and exploring romantic and sexual relationships in adolescence, influence face‐processing behavior.
THE QUANTITATIVE IMPORTANCE OF OPENNESS IN DEVELOPMENT
Authors: Cai Wenbiao , Ravikumar B. , Riezman Raymond G.
Published: April 2015

This paper deals with a classic development question: how can the process of economic development—transition from stagnation in a traditional technology to industrialization and prosperity with a modern technology—be accelerated? Lewis (1954) and Rostow (1956) argue that the pace of industrialization is limited by the rate of capital formation which in turn is limited by the savings rate of workers close to subsistence. We argue that access to capital goods in the world market can be quantitatively important in speeding up the transition. We develop a parsimonious open‐economy model where traditional and modern technologies coexist (a dual economy in the sense of Lewis 1954). We show that a decline in the world price of capital goods in an open economy increases the rate of capital formation and speeds up the pace of industrialization relative to a closed economy that lacks access to cheaper capital goods. In the long run, the investment rate in the open economy is twice as high as in the closed economy and the per capita income is 23% higher. (JEL O11, F43, O14)
Sulcus subarachnoid hemorrhage is a common stroke subtype in patients with implanted left ventricular assist devices
Authors: Sakaguchi M. , Kitagawa K. , Okazaki S. , Yoshioka D. , Sakata Y. , Mochizuki H. , Sawa Y. , Yoshimine T.
Published: April 2015

Background and purpose

Stroke is one of the major complications observed in patients with an implanted left ventricular assist device (LVAD). The purpose of this study was to clarify the types and characteristics of acute stroke in patients after LVAD implantation by using brain computed tomography (CT) findings.

Methods

Between 2005 and 2012, 110 consecutive patients who underwent LVAD implantation were reviewed. The most commonly used device was the pulsatile extracorporeal LVAD. Amongst them, 49 patients suffered from acute stroke at least once with a total of 115 stroke events. The clinical categories, lesion sites, laboratory data and CT findings of each acute stroke event were analyzed.

Results

Cerebral infarction (35 patients, 72 events), cerebral hemorrhage (25 patients, 31 events) and subarachnoid hemorrhage (SAH) (23 patients, 33 events) were identified. A mean of 2.3 stroke events occurred per person. Of the 72 infarction events, multiple infarctions were observed in 29 events. Of the cerebral hemorrhage events (n = 31), almost all were subcortical lesions (n = 27) and none were observed in the basal ganglia. Of the 23 patients with SAH events (n = 33), SAH localized within a single sulcus, sulcus SAH, was observed in 25 events.

Conclusions

Computed tomography findings of acute stroke after implantation of an LVAD are characteristically multifocal cortical lesions, regardless of brain infarction and hemorrhage. Unexpectedly, sulcus SAH was a common stroke subtype in patients with implanted LVADs. Sulcus SAH should be carefully examined in patients after LVAD implantation, when they complain of non‐specific neurological complaints.
Oncometabolites: tailoring our genes
Authors: Nowicki Stefan , Gottlieb Eyal
Published: April 2015

Increased glucose metabolism in cancer cells is a phenomenon that has been known for over 90 years, allowing maximal cell growth through faster ATP production and redistribution of carbons towards nucleotide, protein and fatty acid synthesis. Recently, metabolites that can promote tumorigeneis by altering the epigenome have been identified. These ‘oncometabolites’ include the tricarboxylic acid cycle metabolites succinate and fumarate, whose levels are elevated in rare tumours with succinate dehydrogenase and fumarate hydratase mutations, respectively. 2‐Hydroxyglutarate is another oncometabolite; it is produced de novo as a result of the mutation of isocitrate dehydrogenase, and is commonly found in gliomas and acute myeloid leukaemia. Interestingly, the structural similarity of these oncometabolites to their precursor metabolite, α‐ketoglutarate, explains the tumorigenic potential of these metabolites, by competitive inhibition of a superfamily of enzymes called the α‐ketoglutarate‐dependent dioxygenases. These enzymes utilize α‐ketoglutarate as a cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen biosynthesis, and modulation of the epigenome. They include enzymes that are involved in regulating gene expression via DNA and histone tail demethylation. In this review, we will focus on the link between metabolism and epigenetics, and how we may target oncometabolite‐induced tumorigenesis in the future.
Reconstructing a Carboniferous inferred coral–alcyonarian association using a biomineralogical approach
Authors: Coronado I. , Fernández‐Martínez E. , Rodríguez S. , Tourneur F.
Published: April 2015

The taxonomic assignation and ecological implications of the genusSyringoalcyonTermier & Termier, 1945 have been a palaeontological problem for a long time. Carboniferous material from Morocco and Spain has been studied using a biomineralogical approach by means of petrographic microscopy,SEM,AFM,EMPAandCIPmicroscopy analysis. Detailed morphological, structural, chemical composition and crystallographic data enable a deeper understanding of the nature ofSyringoalcyon. The coral walls and the so‐called epithecal scales exhibit conspicuous differences in microstructure (lamellae and holacanthine fibres in the coral vs. single crystal in scales), nanostructure (pill‐shaped vs. granule‐shaped nanocrystals), composition (LMCvs.HMC) and crystallographic orientation. The results of these analyses imply thatSyringoalcyonis an association between the tabulate coralSyringoporaand an epibiont. They also suggest that the epibiont was an alcyonarian (a rare occurrence in the fossil record) that was attached to the syringoporoid. This work highlights the utility of the biomineralizational approaches for solving palaeontological problems, such as systematic affinities, and for advancing knowledge of the evolution of biocrystallization processes.
Safety of radiation exposure after radiosynovectomy in paediatric patients with haemophilia
Authors: Rodriguez‐Merchan E. C. , Valentino L. A.
Published: April 2015

Many paediatric patients with haemophilia who might benefit from radiosynovectomy (RS) for the control of synovitis do not undergo the procedure as there is controversy in the literature regarding the safety of radiation exposure after two cases of acute lymphocytic leukaemia in children with haemophilia treated with 32P RS were reported. The purpose of this review was to analyse the safety of RS in paediatric patients with haemophilia and provide a risk‐benefit assessment, which practitioners could apply to their patients. Children undergoing knee RS receive a radiation dose of approximately 0.74 mSv (90 megabecquerels‐MBq) and elbow and ankle RSs a dose of approximately 0.32 mSv (30–40 MBq). The radiation dose from natural sources is approximately 2 mSv and the recommended limit for patients (apart from natural sources) is 1 mSv per year. The lifetime cancer risk increases about 0.5% per 100 mSv per year. Considering the risks and benefits of RS, the authors recommend that clinicians consider this procedure in children with inhibitors or in patients without inhibitors when bleeding is recurrent and persistent despite aggressive factor replacement.
The features of clearance in recombinant factor IX (BeneFIX®)
Authors: Suzuki N. , Takedani H. , Hirakawa A. , Ushijima Y. , Matsushita T.
Published: April 2015

Introduction

Dosage adjustment is very important to perform continuous infusion (CI) of recombinant factor IX (rFIX) concentrates more effectively and economically, and clearance (CL) is strongly related to the infusion rate. However, previous reports have shown that the CL of rFIX concentrates varies widely (4.2–11.4 mL kg−1 h−1).

Aim

The goal of this study was to gain a better understanding of the CL of the rFIX concentrate (BeneFIX®) to precisely set the infusion rate of rFIX concentrates.

Methods

We estimated CLs by five different calculation approaches: from area under the blood concentration–time curve (AUC), from in vivo recovery (IVR) and half‐life, from actual FIX activity value during CI, and from the simulation by one‐compartment model in seven patients with haemophilia B.

Results

The mean CL calculated from AUC was 3.8 ± 0.4 mL kg−1 h−1 (range = 3.3–4.3 mL kg−1 h−1).

Conclusion

The mean CL calculated from IVR and distribution half‐life was 4.4 ± 0.4 mL kg−1 h−1 (range = 4.0–5.1 mL kg−1 h−1). The mean CL calculated from IVR and terminal half‐life was 2.1 ± 0.5 mL kg−1 h−1 (range = 1.7–2.8 mL kg−1 h−1). The mean CL during CI was 4.9 ± 0.6 mL kg−1 h−1 (range = 4.2–5.6 mL kg−1 h−1). In addition, when we simulated the theoretical CL using a one‐compartment model, the adjusted mean CL during CI was 4.8 ± 0.5 mL kg−1 h−1 (range = 4.0–5.4 mL kg−1 h−1). The CL obtained from distribution half‐life was comparable to the CL during CI, while the CL calculated from terminal half‐life did not reflect actual CL. Further, the rFIX concentrate was characterized by a one‐compartment model under certain conditions.
Significance of viral status on prognosis of hepatitis B‐related hepatocellular carcinoma after curative resection in East Asia
Authors: Qu Li‐Shuai , Zhang Hai‐Feng
Published: April 2015

Tumor recurrence remains one major obstacle for further improving the prognosis of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients after curative liver resection. It has been widely reported that tumor size, positive surgical margin, macroscopic vascular invasion, tumor–node–metastasis stage and Edmondson's grade were significantly related to HCC recurrence. However, the association between HCC recurrence and important viral factors, including the HBV DNA levels, status of hepatitis B surface antigen and hepatitis B e‐antigen, levels of cccDNA and hepatitis B core‐related antigen, viral genotypes and specific viral sequence mutations remained controversial. Meanwhile, studies on the effect of postoperative adjuvant antiviral therapy on HCC recurrence have been relatively limited and have yielded conflicting results. Identification of certain viral risk factors for HCC recurrence and stratification of patient risk are very important to perform future surveillance programs. As a HBV hyperendemic region, the majority of HBV‐related HCC patients develop in East Asia. In this article, we thus systematically reviewed the risk of important viral factors involved in recurrent carcinogenesis and the role of adjuvant antiviral therapy in preventing tumor recurrence in this area.
Blood markers of oxidative stress predict weaning failure from mechanical ventilation
Authors: Verona Cléber , Hackenhaar Fernanda S. , Teixeira Cassiano , Medeiros Tássia M. , Alabarse Paulo V. , Salomon Tiago B. , Shüller Ártur K. , Maccari Juçara G. , Condessa Robledo Leal , Oliveira Roselaine P. , Rios Vieira Silvia R. , Benfato Mara S.
Published: April 2015

Patients undergoing mechanical ventilation (MV) often experience respiratory muscle dysfunction, which complicates the weaning process. There is no simple means to predict or diagnose respiratory muscle dysfunction because diagnosis depends on measurements in muscle diaphragmatic fibre. As oxidative stress is a key mechanism contributing to MV‐induced respiratory muscle dysfunction, the aim of this study was to determine if differences in blood measures of oxidative stress in patients who had success and failure in a spontaneous breathing trial (SBT) could be used to predict the outcome of MV. This was a prospective analysis of MV‐dependent patients (≥72 hrs; n = 34) undergoing a standard weaning protocol. Clinical, laboratory and oxidative stress analyses were performed. Measurements were made on blood samples taken at three time‐points: immediately before the trial, 30 min. into the trial in weaning success (WS) patients, or immediately before return to MV in weaning failure (WF) patients, and 6 hrs after the trial. We found that blood measures of oxidative stress distinguished patients who would experience WF from patients who would experience WS. Before SBT, WF patients presented higher oxidative damage in lipids and higher antioxidant levels and decreased nitric oxide concentrations. The observed differences in measures between WF and WS patients persisted throughout and after the weaning trial. In conclusion, WF may be predicted based on higher malondialdehyde, higher vitamin C and lower nitric oxide concentration in plasma.
Acacetin inhibits expression of matrix metalloproteinases via a MAPK‐dependent mechanism in fibroblast‐like synoviocytes
Authors: Chen Wei‐Ping , Yang Zhi‐Gao , Hu Peng‐Fei , Bao Jia‐Peng , Wu Li‐Dong
Published: April 2015

It is well known that rheumatoid arthritis (RA) is an autoimmune joint disease in which fibroblast‐like synoviocytes (FLSs) play a pivotal role. In this study, we investigated the anti‐arthritic properties of acacetin in FLSs. The expression of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐13 were investigated by quantitative RT‐PCR and western blot at gene and protein levels. At the same time, the phosphorylation of mitogen‐activated protein kinases (MAPK) was investigated. The DNA‐binding activity of NF‐κB was investigated by electrophoretic mobility shift assay. We found that acacetin inhibits p38 and JNK phosphorylation and reduces MMP‐1, MMP‐3 and MMP‐13 expression in interleukin‐1β‐induced FLSs. Our results suggest that acacetin has antiarthritic effects in FLSs. Thus, acacetin should be further studied for the treatment of arthritis.
Cardiac regenerative potential of cardiosphere‐derived cells from adult dog hearts
Authors: Hensley Michael Taylor , de Andrade James , Keene Bruce , Meurs Kathryn , Tang Junnan , Wang Zegen , Caranasos Thomas G. , Piedrahita Jorge , Li Tao‐Sheng , Cheng Ke
Published: April 2015

The regenerative potential of cardiosphere‐derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin‐induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM.
Improved Zernike‐type phase contrast for transmission electron microscopy
Authors: KOECK P.J.B.
Published: April 2015

Zernike phase contrast has been recognized as a means of recording high‐resolution images with high contrast using a transmission electron microscope. This imaging mode can be used to image typical phase objects such as unstained biological molecules or cryosections of biological tissue. According to the original proposal discussed in Danev and Nagayama (2001) and references therein, the Zernike phase plate applies a phase shift of π/2 to all scattered electron beams outside a given scattering angle and an image is recorded at Gaussian focus or slight underfocus (below Scherzer defocus). Alternatively, a phase shift of ‐π/2 is applied to the central beam using the Boersch phase plate. The resulting image will have an almost perfect contrast transfer function (close to 1) from a given lowest spatial frequency up to a maximum resolution determined by the wave length, the amount of defocus and the spherical aberration of the microscope. In this paper, I present theory and simulations showing that this maximum spatial frequency can be increased considerably without loss of contrast by using a Zernike or Boersch phase plate that leads to a phase shift between scattered and unscattered electrons of only π /4, and recording images at Scherzer defocus. The maximum resolution can be improved even more by imaging at extended Scherzer defocus, though at the cost of contrast loss at lower spatial frequencies.
Alterations of Functional Connectivity Among Resting‐State Networks in Hypothyroidism
Authors: Singh S. , Kumar M. , Modi S. , Kaur P. , Shankar L. R. , Khushu S.
Published: April 2015

Hypothyroidism affects brain functioning as suggested by various neuroimaging studies. The primary focus of the present study was to examine whether hypothyroidism would impact connectivity among resting‐state networks (RSNs) using resting‐state functional magnetic resonance imaging (rsfMRI). Twenty‐two patients with hypothyroidism and 22 healthy controls were recruited and scanned using rsfMRI. The data were analysed using independent component analysis and a dual regression approach that was applied on five RSNs that were identified using fsl software (http://fsl.fmrib.ox.ac.uk). Hypothyroid patients showed significantly decreased functional connectivity in the regions of the right frontoparietal network (frontal pole), the medial visual network (lateral occipital gyrus, precuneus cortex and cuneus) and the motor network (precentral gyrus, postcentral gyrus, precuneus cortex, paracingulate gyrus, cingulate gyrus and supramarginal gyrus) compared to healthy controls. The reduced functional connectivity in the right frontoparietal network, the medial visual network and the motor network suggests neurocognitive alterations in hypothyroid patients in the corresponding functions. However, the study would be further continued to investigate the effects of thyroxine treatment and correlation with neurocognitive scores. The findings of the present study provide further interesting insights into our understanding of the action of thyroid hormone on the adult human brain.
Profound Changes in Sex Hormone Levels during Cross-Sex Hormone Therapy of Transsexuals do not Alter Serum Cholesterol Acceptor Capacity
Authors: Wultsch Anna , Kaufmann Ulrike , Ott Johannes , Stojakovic Tatjana , Scharnagl Hubert , Stangl Herbert , Strobl Witta Monika
Published: April 2015

Introduction

Men and postmenopausal women exhibit a higher risk for atherosclerosis than premenopausal women. These differences were often attributed to sex steroids, but the role of estrogen and testosterone in atherosclerosis are more complex than anticipated. Cross-sex hormone therapy of transsexuals is an interesting model, which has been used to study hormonal effects on serum lipid profile, insulin resistance, and body composition. However, studies on macrophage cholesterol efflux, the first step in reverse cholesterol transport, are not available.

Aim

The aim of this study was to evaluate the effect of cross-sex hormone therapy in transsexuals on the capacity of serum to accept cholesterol from macrophages.

Methods

Cholesterol acceptor capacity (CAC) of serum from transsexuals before and after at least 6 months of hormone treatment was measured using macrophage tissue culture models.

Main Outcome Measures

CAC of serum using the human acute monocytic leukemia cell line (THP-1 cells).

Results

Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not increased, but decreased after hormone therapy. Serum from female to male (FtM) transsexuals showed no changes in CAC.

Conclusions

Despite drastic changes in hormone status, no increase in CAC was detected in MtF patients, and no alteration in CAC was seen in FtM patients. These data further challenge the traditional view that estrogen and testosterone exert beneficial and detrimental effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis.
The management of risk arising from the use of antimicrobial agents in veterinary medicine in EU/EEA countries – a review
Authors: Törneke K. , Torren‐Edo J. , Grave K. , Mackay D. K. J.
Published: April 2015

Antimicrobials are essential medicines for the treatment of many microbial infections in humans and animals. Only a small number of antimicrobial agents with new mechanisms of action have been authorized in recent years for use in either humans or animals. Antimicrobial resistance (AMR) arising from the use of antimicrobial agents in veterinary medicine is a concern for public health due to the detection of increasing levels of resistance in foodborne zoonotic bacteria, particularly gram‐negative bacteria, and due to the detection of determinants of resistance such as Extended‐spectrum beta‐lactamases (ESBL) in bacteria from animals and in foodstuffs of animal origin. The importance and the extent of the emergence and spread of AMR from animals to humans has yet to be quantified. Likewise, the relative contribution that the use of antimicrobial agents in animals makes to the overall risk to human from AMR is currently a subject of debate that can only be resolved through further research. Nevertheless, risk managers have agreed that the impact on public health of the use of antimicrobials in animals should be minimized as far as possible and a variety of measures have been introduced by different authorities in the EU to achieve this objective. This article reviews a range of measures that have been implemented within European countries to reduce the occurrence and the risk of transmission of AMR to humans following the use of antimicrobial agents in animals and briefly describes some of the alternatives to the use of antimicrobial agents that are being developed.
Integration of genetic and physical maps of the Primula vulgaris S locus and localization by chromosome in situ hybridization
Authors: Li Jinhong , Webster Margaret A. , Wright Jonathan , Cocker Jonathan M. , Smith Matthew C. , Badakshi Farah , Heslop‐Harrison Pat , Gilmartin Philip M.
Published: April 2015

Heteromorphic flower development in Primula is controlled by the S locus. The S locus genes, which control anther position, pistil length and pollen size in pin and thrum flowers, have not yet been characterized. We have integrated S‐linked genes, marker sequences and mutant phenotypes to create a map of the P. vulgaris S locus region that will facilitate the identification of key S locus genes. We have generated, sequenced and annotated BAC sequences spanning the S locus, and identified its chromosomal location.

We have employed a combination of classical genetics and three‐point crosses with molecular genetic analysis of recombinants to generate the map. We have characterized this region by Illumina sequencing and bioinformatic analysis, together with chromosome in situ hybridization.

We present an integrated genetic and physical map across the P. vulgaris S locus flanked by phenotypic and DNA sequence markers. BAC contigs encompass a 1.5‐Mb genomic region with 1 Mb of sequence containing 82 S‐linked genes anchored to overlapping BACs. The S locus is located close to the centromere of the largest metacentric chromosome pair.

These data will facilitate the identification of the genes that orchestrate heterostyly in Primula and enable evolutionary analyses of the S locus.
Pulmonary Arteriovenous Malformations in Dyskeratosis Congenita
Authors: Samuel Bennett P. , Duffner Ulrich A. , Abdel‐Mageed Aly S. , Vettukattil Joseph J.
Published: April 2015

Pulmonary arteriovenous malformations (PAVMs) are rare lesions known to cause cyanosis due to abnormal communication between the pulmonary arteries and veins. They are commonly seen in association with hereditary hemorrhagic telangiectasia, congenital heart disease, hepatopulmonary syndrome, and portopulmonary shunting, but rarely in patients with dyskeratosis congenita (DC). We describe a patient previously diagnosed with DC confirmed to have microscopic PAVMs after bone marrow transplantation and discuss possible pathogenic mechanisms.
Bone marrow transplant for X‐linked protoporphyria with severe hepatic fibrosis
Authors: Butler David F. , Ginn Kevin F. , Daniel James F. , Bloomer Joseph R. , Kats Alexander , Shreve Nancy , Myers Gary D.
Published: April 2015

XLP is an erythroid porphyria that results in variable cutaneous photosensitivity due to accumulation of protoporphyrin. The genetic defect in XLP is mutation of the gene ALAS2, resulting in gain of function for the erythroid enzyme 5‐aminolevulinate synthase 2. Previous reports have shown that protoporphyrin‐induced liver disease may also occur in XLP, occasionally severe enough to warrant liver transplantation; however, transplantation may be followed by injury to the graft due to continued presence of the underlying metabolic disorder in the bone marrow. We present a case of XLP with severe liver disease successfully treated with HPCT to avoid liver transplantation. The case also demonstrates the feasibility of reduced intensity transplant to provide engraftment sufficient for correction of porphyria and tolerability of reduced intensity conditioning containing TLI in the face of severe liver injury.
Identifying the immunomodulatory components of helminths
Authors: Shepherd C. , Navarro S. , Wangchuk P. , Wilson D. , Daly N. L. , Loukas A.
Published: April 2015

Immunomodulatory components of helminths offer great promise as an entirely new class of biologics for the treatment of inflammatory diseases. Here, we discuss the emerging themes in helminth‐driven immunomodulation in the context of therapeutic drug discovery. We broadly define the approaches that are currently applied by researchers to identify these helminth molecules, highlighting key areas of potential exploitation that have been mostly neglected thus far, notably small molecules. Finally, we propose that the investigation of immunomodulatory compounds will enable the translation of current and future research efforts into potential treatments for autoimmune and allergic diseases, while at the same time yielding new insights into the molecular interface of host–parasite biology.