bluuebunny/crossref_metadata_2025 huggingface dataset:
The Placenta in Toxicology. Part III
Authors: Cline J. Mark , Dixon Darlene , Ernerudh Jan , Faas Marijke M. , Göhner Claudia , Häger Jan-Dirk , Markert Udo R. , Pfarrer Christiane , Svensson-Arvelund Judit , Buse Eberhard
Published: March 2013

This short review is derived from the peer-reviewed literature and the experience and case materials of the authors. Brief illustrated summaries are presented on the gross and histologic normal anatomy of rodent and macaque placentas, including typical organ weights, with comments on differences from the human placenta. Common incidental findings, background lesions, and induced toxic lesions are addressed, and a recommended strategy for pathologic evaluation of placentas is provided.
Increasing Recognition of Happiness in Ambiguous Facial Expressions Reduces Anger and Aggressive Behavior
Authors: Penton-Voak Ian S. , Thomas Jamie , Gage Suzanne H. , McMurran Mary , McDonald Sarah , Munafò Marcus R.
Published: March 2013

The ability to identify emotion in other people is critical to social functioning. In a series of experiments, we explored the relationship between recognition of emotion in ambiguous facial expressions and aggressive thoughts and behavior, both in healthy adults and in adolescent youth at high risk of criminal offending and delinquency. We show that it is possible to experimentally modify biases in emotion recognition to encourage the perception of happiness over anger in ambiguous expressions. This change in perception results in a decrease in self-reported anger and aggression in healthy adults and high-risk youth, respectively, and also in independently rated aggressive behavior in high-risk youth. We obtained similar effects on mood using two different techniques to modify biases in emotion perception (feedback-based training and visual adaptation). These studies provide strong evidence that emotion processing plays a causal role in anger and the maintenance of aggressive behavior.
Step-up procedures for non-inferiority tests with multiple experimental treatments
Authors: Kwong Koon Shing , Cheung Siu Hung , Hayter Anthony J
Published: March 2013

Non-inferiority (NI) trials are becoming more popular. The NI of a new treatment compared with a standard treatment is established when the new treatment maintains a substantial fraction of the treatment effect of the standard treatment. A valid NI trial is also required to show assay sensitivity, the demonstration of the standard treatment having the expected effect with a size comparable to those reported in previous placebo-controlled studies. A three-arm NI trial is a clinical study that includes a new treatment, a standard treatment and a placebo. Most of the statistical methods developed for three-arm NI trials are designed for the existence of only one new treatment. Recently, a single-step procedure was developed to deal with NI trials with multiple new treatments with the overall familywise error rate controlled at a specified level. In this article, we extend the single-step procedure to two new step-up procedures for NI trials with multiple new treatments. A comparative study of test power shows that both proposed step-up procedures provide a significant improvement of power when compared to the single-step procedure. One of the two proposed step-up procedures also allows the flexibility of allocating different error rates between the sensitivity hypothesis and the NI hypotheses so that the assignment of fewer patients to the placebo becomes possible when designing NI trials. We illustrate the new procedures using data from a clinical trial.
Just a wind-up? Ethnicity, religion and prejudice in Scottish football-related comedy
Authors: Reid Irene A
Published: March 2013

This article probes how media representations of football in Scotland sustain the hegemonic ideologies associated with ethnicity and religion. The paper probes the football-related comedy output of one radio programme; radio output and football comedy are both neglected cultural material in studies of sport in Scotland. It argues that ambiguity and allusive language in comedy construct multiple interpretative possibilities that can demean the social and cultural identity of particular groups in society. The discussion analyses specific sketches from the Scottish radio comedy show Watson’s Wind Up. It is concluded that although humorous, these sketches reveal how ideas, myths and stereotypes that coalesce round Celtic FC and the Irish-descended and Catholic communities in Scotland reinforce and sustain anti-Irish and anti-Catholic bigotry.
A Fraught Exchange? U.S. Media on Chinese International Undergraduates and the American University
Authors: Abelmann Nancy , Kang Jiyeon
Published: March 2013

In this article, we analyze the U.S. media discourse on Chinese international undergraduate students, the largest international student group since 2009. The discourse describes a market exchange, but reveals a struggle between: on the one hand, “a fair exchange”—between excellent Chinese students and world-class American liberal education; and, on the other hand, a “faltering exchange”—between ethically suspect and inassimilable Chinese students and a mercenary and possibly mediocre American university. We argue that this media reporting builds on long-standing seemingly contradictory images of an alluring China market and a threatening “Yellow Peril.” We suggest that this media contest indexes the challenges of campus internationalization; just as the media questions real value on both sides of the exchange, so too is the campus encounter fragile and fraught.
A micro-structural model for prediction of void initiation in superplastic forming
Authors: Nedoushan Reza Jafari , Farzin Mahmoud , Mashayekhi Mohammad
Published: March 2013

Superplastic forming has been used to produce complex parts without local thinning. Cavitations that occur during this procedure can reduce the quality of products. In this paper, a model is proposed to predict void initiation in superplastic forming based on the study of dominant micro-mechanisms. For this purpose, a constitutive model is proposed that considers micro-mechanisms of superplastic forming including: grain interior deformation, grain boundary sliding and grain boundary diffusion. The possibility of void initiation around a second phase particle is evaluated by calculating relative velocity between two adjacent grains and mass transportation around the particle due to diffusion. The proposed model is calibrated for an Aluminum alloy at 500℃ and 550℃. Then the model is used to predict void numbers in various strains and strain rates at these temperatures. Model predictions are in excellent agreement with experimental data. It is shown that grain boundary sliding has a significant role in void initiation of superplastic materials.
Methodological Advances in the Analysis of Bipartite Networks
Authors: Piepenbrink Anke , Gaur Ajai S.
Published: March 2013

Network-based research in the management field largely assumes one-mode (unipartite) networks, despite the widespread presence of two-mode (bipartite) networks. In empirical work, scholars usually project a bipartite network onto a unipartite network, ignoring issues related to the interdependence of ties and potential loss of information. Yet new advances in measures and methods related to bipartite networks in the fields of sociology, physics, and biology may make such tactics unnecessary. This article presents an overview of three research streams related to bipartite networks, namely, (a) refinements related to the projections of bipartite networks onto unipartite networks; (b) the extension of networks measures from unipartite networks to bipartite networks, with a focus on clustering coefficients; and (c) approaches unique to bipartite networks, such as nestedness. We apply these approaches and compare the findings of a traditional unipartite network analysis using both a simple example and a sample of 10,223 directors of 1,528 Indian firms in 2009.
Socioeconomic differences in disability retirement in Finland: The contribution of ill-health, health behaviours and working conditions
Authors: Polvinen Anu , Gould Raija , Lahelma Eero , Martikainen Pekka
Published: March 2013

Aims: Socioeconomic differences in disability retirement are large. In this study, the main interest was to find out the contribution of diseases, self-rated health, health behaviours and working conditions to socioeconomic differences in disability retirement. Methods: The data are from the nationally-representative Health 2000 Survey to which register-based retirement data have been linked. These data include 3674 persons aged 30–62 years who were employed at baseline. Of the participants, 363 ended up in disability retirement during the follow-up period 2000–2009. Cox regression analysis was used to calculate hazard ratios and their 95% confidence intervals. Results: The risk of all-cause disability retirement was higher among manual workers (HR for men 2.44, 95% CI 1.64–3.63, women 2.33, 1.57–3.44) than upper-grade non-manual employees. Ill-health and physical working conditions contributed to the socioeconomic differences in disability retirement. The importance of physical working conditions was seen in particular among those aged 50 years or over and those in disability retirement due to musculoskeletal diseases. The contribution of self-rated health was stronger in older than younger disability retirees. Conclusions: Our findings suggest that preventing ill-health and improving working conditions, especially among the lower socioeconomic classes, would help reduce socioeconomic differences in disability retirement.
An integrated executable architecture framework for System of Systems development
Authors: Helle Philipp , Giblett Ian , Levier Pascal
Published: March 2013

This paper presents a framework for integrated executable architectures, which is the integration of architecture modelling tools and simulation tools. This framework allows the use of executable architectures during the conceptual analysis and design phases in order to address system complexity at an early stage of the development. The proposed concept of integrated executable architecture enables a dynamic combination of the formerly separated and static areas of business processes, system design and resource modelling. It provides time-based, dynamic visualisation of system behaviour by combining business process simulation, system simulation and synthetic environments. This allows an early understanding of emergent behaviour, time-dependent behaviour and performance estimation of the architecture.
Governing Through Privacy: Authoritarian Liberalism, Law, and Privacy Knowledge
Authors: Lippert Randy K. , Walby Kevin
Published: March 2013

In this article, we examine the production of privacy knowledge and uses of privacy law in relation to liberal governmentality. Understanding liberal governmentality remains critical insofar as authoritarian practices and liberalism are intertwined. We argue the birth of privacy studies and the rise of the notion of ‘privacy by design’ demonstrate a coupling of security and privacy and the embedding of privacy protocol in surveillance technologies consistent with authoritarian liberalism. We illustrate these arguments through analysis of cases pertaining to public camera surveillance and access to information processes (ATIP) in Canada. The growing prevalence of privacy as an object of knowledge and as a means of governance raise questions about its utility as a remedy for surveillance and begins to reveal how authoritarian practices are incorporated within liberalism.
“She’s Leaving Home . . .” Antecedents, Consequences, and Cultural Patterns in the Leaving Home Process
Authors: Seiffge-Krenke Inge
Published: March 2013

In the past, the tasks of establishing psychological and practical independence were linked in time. Nowadays, these transitions are no longer successively manageable sequences; rather, they are characterized by fluctuations, discontinuities, and reversals. In this review, research findings on factors contributing to the diversity in emerging adults’ leaving home patterns (including early leaving, late leaving, or continued residence in the parents’ home) are summarized. These findings show that although culture, gender, social class, and education shape leaving home patterns, individual factors (e.g., emerging adults’ attachment representations or their progress in the domains of love and work), and parenting strategies that essentially keep the child emotionally and physically in close proximity are also influential. The review reveals that leaving home is an important developmental task for both emerging adult children and their parents and illustrates how linked their lives are.
Life Authorship
Authors: McAdams Dan P.
Published: March 2013

A central psychological challenge of emerging adulthood is the construction and internalization of a self-defining life story or narrative identity. In becoming an author for one’s own life, the emerging adult develops a personal narrative that selectively reconstructs the past and imagines the future in such a way as to provide life with purpose, meaning, and a sense of temporal coherence. This article sketches the main themes and processes involved in the development of narrative identity in emerging adulthood by briefly reviewing empirical studies and describing two notable case examples—Barack Obama and George W. Bush. Both Obama and Bush sought to discover and/or compose self-defining life narratives during their emerging adulthood years. Despite their many differences, both ended up drawing upon important social relationships and deep cultural sources to develop powerful stories of personal redemption—in Obama’s case a story of redemption through liberation and self-discovery, and in Bush’s case a story of redemption through recovery, atonement, and the achievement of self-regulation. As illustrated in the case examples, the development of narrative identity should set the psychological stage for meeting the daunting life challenges of the 30s and midlife.
Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice through a Foxp3-independent mechanism that relies on IL-10
Authors: Oliveira Vanessa G. , Agua-Doce Ana , Curotto de Lafaille Maria A. , Lafaille Juan J. , Graca Luis
Published: March 2013

Key Points

An adjuvant (alum), known to boost immune responses, can be used to facilitate a tolerogenic protocol. Nondepleting anti-CD4 can lead to Foxp3+ regulatory T-cell–independent tolerance that relies on IL-10.
Bovine HEXIM1 inhibits bovine immunodeficiency virus replication through regulating BTat-mediated transactivation
Authors: Guo Hong-yan , Ma Yong-gang , Gai Yuan-ming , Liang Zhi-bin , Ma Jing , Su Yang , Zhang Qi-cheng , Chen Qi-min , Tan Juan
Published: March 2013

The bovine immunodeficiency virus (BIV) transactivator (BTat) recruits the bovine cyclin T1 (B-cyclin T1) to the LTR to facilitate the transcription of BIV. Here, we demonstrate that bovine hexamethylene bisacetamide (HMBA)-induced protein 1 (BHEXIM1) inhibits BTat-mediated BIV LTR transcription. The results of in vivo and in vitro assays show direct binding of BHEXIM1 to the B-cyclin T1. These results suggest that the repression arises from BHEXIM1-BTat competition for B-cyclin T1, which allows BHEXIM1 to displace BTat from B-cyclin T1. Furthermore, we found that the C-terminal region and the centrally located region of BHEXIM1 are required for BHEXIM1 to associate with B-cyclin T1. Knockdown of BHEXIM1 enhances BIV replication. Taken together, our study provides the first clear evidence that BHEXIM1 is involved in BIV replication through regulating BTat-mediated transactivation.
TPMS: a set of utilities for querying collections of gene trees
Authors: Bigot Thomas , Daubin Vincent , Lassalle Florent , Perrière Guy
Published: March 2013

Background

The information in large collections of phylogenetic trees is useful for many comparative genomic studies. Therefore, there is a need for flexible tools that allow exploration of such collections in order to retrieve relevant data as quickly as possible.

Results

In this paper, we present TPMS (Tree Pattern-Matching Suite), a set of programs for handling and retrieving gene trees according to different criteria. The programs from the suite include utilities for tree collection building, specific tree-pattern search strategies and tree rooting. Use of TPMS is illustrated through three examples: systematic search for incongruencies in a large tree collection, a short study on the Coelomata/Ecdysozoa controversy and an evaluation of the level of support for a recently published Mammal phylogeny.

Conclusion

TPMS is a powerful suite allowing to quickly retrieve sets of trees matching complex patterns in large collection or to root trees using more rigorous approaches than the classical midpoint method. As it is made of a set of command-line programs, it can be easily integrated in any sequence analysis pipeline for an automated use.
Current manufactured cigarette smoking and roll-your-own cigarette smoking in Thailand: findings from the 2009 Global Adult Tobacco Survey
Authors: Benjakul Sarunya , Termsirikulchai Lakkhana , Hsia Jason , Kengganpanich Mondha , Puckcharern Hataichanok , Touchchai Chitrlada , Lohtongmongkol Areerat , Andes Linda , Asma Samira
Published: March 2013

Background

Current smoking prevalence in Thailand decreased from 1991 to 2004 and since that time the prevalence has remained flat. It has been suggested that one of the reasons that the prevalence of current smoking in Thailand has stopped decreasing is due to the use of RYO cigarettes. The aim of this study was to examine characteristics of users of manufactured and RYO cigarettes and dual users in Thailand, in order to determine whether there are differences in the characteristics of users of the different products.

Methods

The 2009 Global Adult Tobacco Survey (GATS Thailand) provides detailed information on current smoking patterns. GATS Thailand used a nationally and regionally representative probability sample of 20,566 adults (ages 15 years and above) who were chosen through stratified three-stage cluster sampling and then interviewed face-to-face.

Results

The prevalence of current smoking among Thai adults was 45.6% for men and 3.1% for women. In all, 18.4% of men and 1.0% of women were current users of manufactured cigarettes only, while 15.8% of men and 1.7% of women were current users of RYO cigarettes only. 11.2% of men and 0.1% of women used both RYO and manufactured cigarettes. Users of manufactured cigarettes were younger and users of RYO were older. RYO smokers were more likely to live in rural areas. Smokers of manufactured cigarettes appeared to be more knowledgeable about the health risks of tobacco use. However, the difference was confounded with age and education; when demographic variables were controlled, the knowledge differences no longer remained. Smokers of manufactured cigarettes were more likely than dual users and those who used only RYO to report that they were planning on quitting in the next month. Users of RYO only appeared to be more addicted than the other two groups as measured by time to first cigarette.

Conclusions

There appears to be a need for product targeted cessation and prevention efforts that are directed toward specific population subgroups in Thailand and include information on manufactured and RYO cigarettes.
Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta
Authors: Cicek Figen Amber , Kandilci Hilmi B , Turan Belma
Published: March 2013

Background

The RhoA/ROCK signaling pathway mediates vascular smooth muscle contraction while endogenous NO induces vasodilation through its inhibition. Since myosin light chain phosphatase (MLCP) and eNOS are targeted by RhoA/ROCK upregulation then turn to lead abnormalities in vasculature, we aimed to examine whether less endothelial NO-production and inhibited eNOS together with an upregulation of RhoA/ROCK signaling pathway in thoracic aorta can play an important role in vascular dysfunction under hyperglycemia.

Methods

We used streptozotocin-injected rats, as a model of type 1 diabetes, and their lean controls to investigate the role of ROCK upregulation in the function of toracic aorta by using electrophysiological and biochemical techniques.

Results

The protein level of ROCK isoform ROCK2 was found to be 2.5-fold higher in endothelium-intact aortic rings of the diabetic rats compared to those of the controls while its level in endothelium-denuded rings was similar among these two groups. Phosphorylation level of eNOS in endothelium-intact rings from the diabetics was 50% less compared to that of the control. ROCK inhibitors, either Y27632 or HA1077, induced concentration-dependent relaxation with a marked left-shift in phenylephrine pre-contracted endothelium-intact rings from either diabetics or high glucose incubated controls while pretreatment of these rings with L-NAME abolished this shift, fully. Moreover, phosphorylation levels of both MLCP and MLC in endothelium-denuded rings were markedly higher in the diabetics than the controls.

Conclusion

We demonstrated that diabetes-induced vascular dysfunction can arise due to either inbition of eNOS, thereby less endothelial NO-production, either directly or indirectly, in part, due to an upregulation of ROCK2 by hyperglycemia. Additionally, our data demonstrate that high phosphorylation levels of both MLC and MLCP in endothelium-denuded rings can be due to a less endothelial NO-production dependent ROCK upregulation in the smooth muscle cells under hyperglycemia, as well.
Genetic diversity and signatures of selection of drug resistance in Plasmodium populations from both human and mosquito hosts in continental Equatorial Guinea
Authors: Mendes Cristina , Salgueiro Patrícia , Gonzalez Vicenta , Berzosa Pedro , Benito Agustin , do Rosário Virgílio E , de Sousa Bruno , Cano Jorge , Arez Ana Paula
Published: March 2013

Background

In Plasmodium, the high level of genetic diversity and the interactions established by co-infecting parasite populations within the same host may be a source of selection on pathogen virulence and drug resistance. As different patterns have already been described in humans and mosquitoes, parasite diversity and population structure should be studied in both hosts to properly assess their effects on infection and transmission dynamics. This study aimed to characterize the circulating populations of Plasmodium spp and Plasmodium falciparum from a combined set of human blood and mosquito samples gathered in mainland Equatorial Guinea. Further, the origin and evolution of anti-malarial resistance in this area, where malaria remains a major public health problem were traced.

Methods

Plasmodium species infecting humans and mosquitoes were identified by nested-PCR of chelex-extracted DNA from dried blood spot samples and mosquitoes. Analysis of Pfmsp2 gene, anti-malarial-resistance associated genes, Pfdhps, Pfdhfr, Pfcrt and Pfmdr1, neutral microsatellites (STR) loci and Pfdhfr and Pfdhps flanking STR was undertaken to evaluate P. falciparum diversity.

Results

Prevalence of infection remains high in mainland Equatorial Guinea. No differences in parasite formula or significant genetic differentiation were seen in the parasite populations in both human and mosquito samples. Point mutations in all genes associated with anti-malarial resistance were highly prevalent. A high prevalence was observed for the Pfdhfr triple mutant in particular, associated with pyrimethamine resistance.

Analysis of Pfdhps and Pfdhfr flanking STR revealed a decrease in the genetic diversity. This finding along with multiple independent introductions of Pfdhps mutant haplotypes suggest a soft selective sweep and an increased differentiation at Pfdhfr flanking microsatellites hints a model of positive directional selection for this gene.

Conclusions

Chloroquine is no longer recommended for malaria treatment in Equatorial Guinea but sulphadoxine-pyrimethamine (SP) remains in use in combination with artesunate and is the only drug recommended in preventive chemotherapy in pregnancy. The high prevalence of point mutations in Pfdhfr and Pfdhps points to the danger of an eventual reduction in the efficacy of SP combined therapy in P. falciparum populations in Equatorial Guinea and to the essential continuous monitoring of these two genes.
Children’s physical activity and parents’ perception of the neighborhood environment: neighborhood impact on kids study
Authors: Tappe Karyn A , Glanz Karen , Sallis James F , Zhou Chuan , Saelens Brian E
Published: March 2013

Background

Physical activity is important to children’s physical health and well-being. Many factors contribute to children’s physical activity, and the built environment has garnered considerable interest recently, as many young children spend much of their time in and around their immediate neighborhood. Few studies have identified correlates of children’s activity in specific locations. This study examined associations between parent report of their home neighborhood environment and children’s overall and location-specific physical activity.

Methods

Parents and children ages 6 to 11 (n=724), living in neighborhoods identified through objective built environment factors as high or low in physical activity environments, were recruited from Seattle and San Diego metropolitan areas, 2007–2009. Parents completed a survey about their child’s activity and perceptions of home neighborhood environmental attributes. Children wore an accelerometer for 7 days. Multivariate regression models explored perceived environment correlates of parent-reported child’s recreational physical activity in their neighborhood, in parks, and in general, as well as accelerometry-based moderate-to-vigorous activity (MVPA) minutes.

Results

Parent-reported proximity to play areas correlated positively with both accelerometery MVPA and parent-reported total child physical activity. Lower street connectivity and higher neighborhood aesthetics correlated with higher reported child activity in the neighborhood, while reported safety from crime and walk and cycle facilities correlated positively with reported child activity in public recreation spaces.

Conclusions

Different aspects of parent’s perceptions of the neighborhood environment appear to correlate with different aspects of children’s activity. However, prioritizing closer proximity to safe play areas may best improve children’s physical activity and, in turn, reduce their risk of obesity and associated chronic diseases.
Maskless and low-destructive nanofabrication on quartz by friction-induced selective etching
Authors: Song Chenfei , Li Xiaoying , Cui Shuxun , Dong Hanshan , Yu Bingjun , Qian Linmao
Published: March 2013

A low-destructive friction-induced nanofabrication method is proposed to produce three-dimensional nanostructures on a quartz surface. Without any template, nanofabrication can be achieved by low-destructive scanning on a target area and post-etching in a KOH solution. Various nanostructures, such as slopes, hierarchical stages and chessboard-like patterns, can be fabricated on the quartz surface. Although the rise of etching temperature can improve fabrication efficiency, fabrication depth is dependent only upon contact pressure and scanning cycles. With the increase of contact pressure during scanning, selective etching thickness of the scanned area increases from 0 to 2.9 nm before the yield of the quartz surface and then tends to stabilise after the appearance of a wear. Refabrication on existing nanostructures can be realised to produce deeper structures on the quartz surface. Based on Arrhenius fitting of the etching rate and transmission electron microscopy characterization of the nanostructure, fabrication mechanism could be attributed to the selective etching of the friction-induced amorphous layer on the quartz surface. As a maskless and low-destructive technique, the proposed friction-induced method will open up new possibilities for further nanofabrication.
A joint design of security and quality-of-service (QoS) provisioning in vehicular ad hoc networks with cooperative communications
Authors: Zhu Li , Yu F Richard , Ning Bin , Tang Tao
Published: March 2013

In vehicular ad hoc networks (VANETs), some distinct characteristics, such as high node mobility, introduce new non-trivial challenges to quality-of-service (QoS) provisioning. Although some excellent works have been done on QoS issues in VANETs, security issues are largely ignored in these works. However, it is know that security always comes at a price in terms of QoS performance degradation. In this article, we consider security and QoS issues jointly for VANETs with cooperative communications. We take an integrated approach of optimizing both security and QoS parameters, and study the tradeoffs between them in VANETs. Specifically, we use recent advances in cooperative communication to enhance the QoS performance of VANETs. In addition, we present a prevention-based security technique that provides both hop-by-hop and end-to-end authentication and integrity protection. We derive the closed-form effective secure throughput considering both security and QoS provisioning in VANETs with cooperative communications. The system is formulated as a partially observable Markov decision process. Simulation results are presented to show that security schemes have significant impacts on the throughput QoS of VANETs, and our proposed scheme can substantially improve the effective secure throughput of VANETs with cooperative communications.
Paclitaxel and cisplatin combined with intensity-modulated radiotherapy for upper esophageal carcinoma
Authors: Tu Lingli , Sun Lan , Xu Yong , Wang Yongsheng , Zhou Lin , Liu Yongmei , Zhu Jiang , Peng Feng , Wei Yuquan , Gong Youling
Published: March 2013

Purpose

This study was conducted to evaluate the effectiveness and safety of intensity-modulated radiotherapy (IMRT) and concurrent paclitaxel plus cisplatin (TP regimen) for upper esophageal carcinoma.

Methods

36 patients of upper esophageal carcinoma were retrospectively analyzed. Patients were treated with IMRT (median 60 Gy) combined with concurrent TP regimen chemotherapy. The Kaplan-Meier analysis was performed in statistical analysis. Toxicities were recorded according to the NCI CTC version 3.0.

Results

36 patients aged 43–73 years (median 57 years). The median follow-up period was 14.0 months. The 1-year and 2-year survival rates were 83.3% and 42.8% respectively. The median progression-free survival (PFS) time and overall survival (OS) time were 12.0 (95% CI: 7.8–16.2 months) and 18.0 months (95% CI: 9.9–26.1 months), respectively. Grade 3 neutropenia, radiation-induced esophagitis and radiodermatitis were observed in 5 (13.9%), 3 (8.3%) and 8 (22.2%) patients respectively. There were two treatment-related deaths due to esophageal perforation and hemorrhea.

Conclusions

For those patients with upper esophageal carcinoma, IMRT combined with concurrent TP regimen chemotherapy was an effective treatment. However, more attention should be paid to the occurrence of perforation and hemorrhea.
Gene Ontology consistent protein function prediction: the FALCON algorithm applied to six eukaryotic genomes
Authors: Kourmpetis Yiannis AI , van Dijk Aalt DJ , ter Braak Cajo JF
Published: March 2013

Background

Gene Ontology (GO) is a hierarchical vocabulary for the description of biological functions and locations, often employed by computational methods for protein function prediction. Due to the structure of GO, function predictions can be self- contradictory. For example, a protein may be predicted to belong to a detailed functional class, but not in a broader class that, due to the vocabulary structure, includes the predicted one.

We present a novel discrete optimization algorithm called Functional Annotation with Labeling CONsistency (FALCON) that resolves such contradictions. The GO is modeled as a discrete Bayesian Network. For any given input of GO term membership probabilities, the algorithm returns the most probable GO term assignments that are in accordance with the Gene Ontology structure. The optimization is done using the Differential Evolution algorithm. Performance is evaluated on simulated and also real data fromArabidopsis thalianashowing improvement compared to related approaches. We finally applied the FALCON algorithm to obtain genome-wide function predictions for six eukaryotic species based on data provided by the CAFA (Critical Assessment of Function Annotation) project.
Impact of enzyme replacement therapy on survival in adults with Pompe disease: results from a prospective international observational study
Authors: Güngör Deniz , Kruijshaar Michelle E , Plug Iris , D’Agostino Ralph B , Hagemans Marloes LC , van Doorn Pieter A , Reuser Arnold JJ , van der Ploeg Ans T
Published: March 2013

Background

Pompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of ERT on the survival of adult patients are currently available. The aim of this study was to assess the effect of ERT on survival in adult patients with Pompe disease.

Methods

Data were collected as part of an international observational study conducted between 2002 and 2011, in which patients were followed on an annual basis. Time-dependent Cox’s proportional hazards models were used for univariable and multivariable analyses.

Results

Overall, 283 adult patients with a median age of 48 years (range, 19 to 81 years) were included in the study. Seventy-two percent of patients started ERT at some time during follow-up, and 28% never received ERT. During follow-up (median, 6 years; range, 0.04 to 9 years), 46 patients died, 28 (61%) of whom had never received ERT. After adjustment for age, sex, country of residence, and disease severity (based on wheelchair and ventilator use), ERT was positively associated with survival (hazard ratio, 0.41; 95% CI, 0.19 to 0.87).

Conclusion

This prospective study was the first to demonstrate the positive effect of ERT on survival in adults with Pompe disease. Given the relatively recent registration of ERT for Pompe disease, these findings further support its beneficial impact in adult patients.
Anthropometric differences among natives of Abuja living in urban and rural communities: correlations with other cardiovascular risk factors
Authors: Adediran Olufemi Sola , Adebayo Philip Babatunde , Akintunde Adeseye Abiodun
Published: March 2013

Background

There is an increase of obesity and other cardiovascular risk factors worldwide, but especially in developing countries where multifaceted transitions are occurring. There is need for more evidence for the cardio-metabolic effect of changing lifestyles and urbanization in Nigeria. This study aimed at defining rural–urban differences in anthropometric parameters in two Nigerian communities of the same ancestral origin and to determine the cardiovascular risk correlates of these anthropometric measurements. This was a cross-sectional epidemiological study using stratified cluster sampling method. We studied 335 and 332 urban and rural dwellers respectively. A complete cardiovascular profile as well as anthropometric measurements was compared between the two populations.

Results

All anthropometric indices considered in this study (weight, BMI, waist circumference, waist circumference/height ratio, abdominal height; biceps, triceps, sub-scapular, abdominal, superior iliac skinfold thicknesses) were significantly higher in urban than in the rural population (p = <0.001). Overweight, obesity and hypertension were significantly prevalent among the urban population (p = <0.001) while there was no significant difference in the prevalence of dyslipidaemia (p = 0.096) and diabetes (p = 0.083) between the two cohorts. Females tend to have a higher chance of obesity than males although there was no gender difference in waist circumference and central skin fold thickness in the rural population. Age was the significant predictor of systolic blood pressure among the rural (R2 = 0.157, β = 0.258, p = 0.016) and urban female population (R2 = 0.201, β = 0.351, p = <0.001) while Abdominal height (R2 = 0.16, β = 0.281, p = 0.001) and waist circumference (R2 = 0.064 β = 0.064, p = .003) were predictors of systolic blood pressure in urban and rural men respectively.

Conclusion

Anthropometric indices were significantly higher among the urban than the rural populations. Cardiovascular risks were equally more prevalent among the urban population. Appropriate health education and lifestyle modification strategies may reduce the increased burden of cardiovascular risk factors associated with rural–urban migration.
Quality of life and pruritus in patients with severe sepsis resuscitated with hydroxyethyl starch long-term follow-up of a randomised trial
Authors: Wittbrodt Piotr , Haase Nicolai , Butowska Dominika , Winding Robert , Poulsen Jesper B , Perner Anders ,   the 6S trial group and the Scandinavian Critical Care Trials Group
Published: March 2013

Introduction

The effects of hydroxyethyl starch (HES) on patient-centered outcome measures have not been fully described in patients with severe sepsis. We assessed health-related quality of life (HRQoL) and the occurrence of pruritus in patients with severe sepsis randomized to resuscitation with HES 130/0.42 or Ringer's acetate.

Methods

We did post hoc analyses of the Danish survivors (n = 295) of the 6S trial using mailed questionnaires on self-perceived HRQoL (Short Form (SF) - 36) and pruritus.

Results

Median 14 months (interquartile range 10 to 18) after randomization, 182 (61%) and 185 (62%) completed questionnaires were obtained for the assessment of HRQoL and pruritus, respectively. Responders were older than nonresponders, but characteristics at randomization of the responders in the HES vs. Ringer's groups were comparable. At follow-up, the patients in the HES group had lower mental component summary scores than those in the Ringer's group (median 45 (interquartile range 36 to 55) vs. 53 (39 to 60), P = 0.01). The group differences were mainly in the scales of vitality and mental health. There was no difference in the physical component summary scores between groups, but patients in the HES group scored worse in bodily pain. Forty-nine percent of patients allocated to HES had experienced pruritus at any time after ICU discharge compared to 43% of those allocated to Ringer's (relative risk 1.13, 95% confidence interval 0.83 to 1.55, P = 0.43).

Conclusions

At long-term follow-up patients with severe sepsis assigned to resuscitation with HES 130/0.42 had worse self-perceived HRQoL than those assigned to Ringer's acetate whereas there were no statistically significant differences in the occurrence of pruritus.
Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing
Authors: O'Rawe Jason , Jiang Tao , Sun Guangqing , Wu Yiyang , Wang Wei , Hu Jingchu , Bodily Paul , Tian Lifeng , Hakonarson Hakon , Johnson W Evan , Wei Zhi , Wang Kai , Lyon Gholson J
Published: March 2013

Background

To facilitate the clinical implementation of genomic medicine by next-generation sequencing, it will be critically important to obtain accurate and consistent variant calls on personal genomes. Multiple software tools for variant calling are available, but it is unclear how comparable these tools are or what their relative merits in real-world scenarios might be.

Methods

We sequenced 15 exomes from four families using commercial kits (Illumina HiSeq 2000 platform and Agilent SureSelect version 2 capture kit), with approximately 120X mean coverage. We analyzed the raw data using near-default parameters with five different alignment and variant-calling pipelines (SOAP, BWA-GATK, BWA-SNVer, GNUMAP, and BWA-SAMtools). We additionally sequenced a single whole genome using the sequencing and analysis pipeline from Complete Genomics (CG), with 95% of the exome region being covered by 20 or more reads per base. Finally, we validated 919 single-nucleotide variations (SNVs) and 841 insertions and deletions (indels), including similar fractions of GATK-only, SOAP-only, and shared calls, on the MiSeq platform by amplicon sequencing with approximately 5000X mean coverage.

Results

SNV concordance between five Illumina pipelines across all 15 exomes was 57.4%, while 0.5 to 5.1% of variants were called as unique to each pipeline. Indel concordance was only 26.8% between three indel-calling pipelines, even after left-normalizing and intervalizing genomic coordinates by 20 base pairs. There were 11% of CG variants falling within targeted regions in exome sequencing that were not called by any of the Illumina-based exome analysis pipelines. Based on targeted amplicon sequencing on the MiSeq platform, 97.1%, 60.2%, and 99.1% of the GATK-only, SOAP-only and shared SNVs could be validated, but only 54.0%, 44.6%, and 78.1% of the GATK-only, SOAP-only and shared indels could be validated. Additionally, our analysis of two families (one with four individuals and the other with seven), demonstrated additional accuracy gained in variant discovery by having access to genetic data from a multi-generational family.

Conclusions

Our results suggest that more caution should be exercised in genomic medicine settings when analyzing individual genomes, including interpreting positive and negative findings with scrutiny, especially for indels. We advocate for renewed collection and sequencing of multi-generational families to increase the overall accuracy of whole genomes.
Clinical Relevance of Combined FSH and AMH Observations in Infertile Women
Authors: Gleicher Norbert , Kim Ann , Kushnir Vitaly , Weghofer Andrea , Shohat-Tal Aya , Lazzaroni Emanuela , Lee Ho-Joon , Barad David H.
Published: March 2013

Context:

FSH and anti-Müllerian hormone (AMH) are, individually, widely used to assess functional ovarian reserve (FOR) but demonstrate discrepancies in efficacy. How predictive they are combined is unknown.

Objective:

The purpose of this study was to assess predictive values of different FSH and AMH combinations on in vitro fertilization (IVF).

Design and Setting:

FSH and AMH levels in patients were categorized as low, normal, and high, based on age-specific 95% confidence intervals. This allowed for establishment of nine combinations of low, normal, or high FSH/AMH patient categories. With use of various statistical methods, patients in individual categories were then compared in outcomes.

Patients:

We investigated 544 consecutive infertility patients in their first IVF cycles.

Interventions:

IVF cycles were managed.

Main Outcome Measures:

Oocyte yields and implantation and pregnancy rates, adjusted for age and fragile X mental retardation 1 (FMR1) genotypes/subgenotypes, were measured.

Results:

The most notable repeated finding was a strong statistical association of the FSH/AMH high/high category (characterized by abnormally high FSH and AMH levels) with favorable IVF outcomes compared with outcomes for other FSH/AMH variations (4.34 times odds of high oocyte yields and 1.93 times odds of clinical pregnancy). Addition of age to the model only minimally further improved the odds of pregnancy to 2.03 times. The positive association with high oocyte yields, however, turned negative (0.75 times lower yields) with addition of FMR1 to the model for women with FSH/AMH high/high and the het-norm/low FMR1 subgenotype compared with women with the norm FMR1 genotype and other FSH/AMH categories.

Conclusions:

In the absence of het-norm/low FMR1, abnormally high FSH and AMH, a seemingly contradictory combination, reflects highly beneficial outcomes in IVF compared with the other FSH/AMH categories, suggesting greater importance of FSH in early follicle maturation than currently recognized. The study also confirms adverse outcome effects of het-norm/low FMR1 and, therefore, the gene's importance for reproductive success.
The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus
Authors: James Rob S. , Staples James F. , Brown Jason C. L. , Tessier Shannon N. , Storey Kenneth B.
Published: March 2013

Hibernation is a crucial strategy of winter survival used by many mammals. During hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle through a series of torpor bouts, each lasting more than a week, during which the animals are largely immobile. Previous hibernation studies have demonstrated that such natural models of skeletal muscle disuse cause limited or no changes in either skeletal muscle size or mechanical performance. However, work loop analysis of skeletal muscle, which provides a realistic assessment of in vivo power output, has not previously been undertaken in mammals that undergo prolonged torpor during hibernation. In the present study, our aim was to assess the effects of 3 months of hibernation on mechanical performance (using the work loop technique) and several biochemical properties that may affect performance. There was no significant difference in soleus muscle power output-cycle frequency curves between winter (torpid) and summer animals. Total antioxidant capacity of gastrocnemius muscle was 156% higher in torpid than summer animals, suggesting one potential mechanism for maintenance of acute muscle performance. Soleus muscle fatigue resistance was significantly lower in torpid than summer animals. Gastrocnemius muscle glycogen content was unchanged. However, state 3 and state 4 mitochondrial respiration rates were significantly suppressed, by 59% and 44% respectively, in mixed hind-limb skeletal muscle from torpid animals compared with summer controls. These findings in hind-limb skeletal muscles suggest that, although maximal mechanical power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance.
High frequency electrical stimulation reveals a p38-mTOR signaling module correlated with force-time integral
Authors: Rahnert Jill A. , Burkholder Thomas J.
Published: March 2013

High frequency electrical stimulation (HFES) leads to muscle hypertrophy, and attention has been drawn to the high forces involved. However, both mechanical and metabolic stresses occur simultaneously, and both stimuli influence signaling cascades related to protein synthesis. This study aimed to identify the immediate signaling correlates of contraction-induced force and metabolic stresses under the hypothesis that HFES induces growth-related signaling through mechanical stimulation. Force-time integral (FTI) signaling in mouse tibialis anterior muscle was examined by separately manipulating the time of contraction to emphasize the metabolic aspect or the force of contraction to emphasize the mechanical aspect. When FTI was manipulated by changing the total time of activation, phosphorylation of p54 JNK, ERK and p70S6kT421/S424 was independent of FTI, while phosphorylation of ACC and p38 correlated with FTI. When FTI was manipulated by changing the force of contraction, p54 JNK, ERK, and p70S6kT421/S424 were again independent of FTI, while phosphorylation of p38 and FAK correlated with FTI. Factor analysis identified a p38-mTOR signaling module that correlated with FTI in both experiments. The consistent link among p38, mTOR and FTI suggests that they form a connected signaling module sensitive to the mechanical aspects of FTI, separate from markers of metabolic load.