bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability modeling and analysis for open source cloud computing
Authors: Tamura Yoshinobu , Kawakami Masaru , Yamada Shigeru
Published: January 2013

At present, cloud computing is attracting attention as a network service to share the computing resources, such as networks, servers, storage, applications, and services. Also, many open source softwares are developed in all parts of the world, e.g. Firefox, Apache HTTP server, Linux, Android, etc. This article focuses on a cloud computing environment by using open source software such as OpenStack and Eucalyptus because of the unify management of data and low cost. This article proposes a new approach to software reliability assessment based on the stochastic differential equations and hierarchical Bayesian modeling in order to consider the interesting aspect of the network status of a cloud computing environment. Also, actual software fault-count data to show numerical examples of software reliability assessment considering the characteristics of network environment is analyzed.
Motivating Music Students
Authors: West Chad
Published: January 2013

John Dewey knew that when students were actively involved in their learning, they were more motivated and achieved higher. Unfortunately, our practices often negatively affect motivation, such as when teachers emphasize competition, social comparison, normative grading criteria, public forms of evaluation, and ability self-assessment. Most recently, researchers have begun exploring motivation through the lenses of (a) how we attribute successes and failures (attribution theory), (b) reasons for achieving (achievement goal theory) and (c) ways in which we seek to satisfy our internal needs (intrinsic motivation theory). This article examines the music education literature within these three seminal social cognitive theories and discusses the implications to music education with respect to (a) locus of control, (b) self-concept and achievement, and (c) motivational ways of engaging students. The article concludes with specific recommendations for increasing student motivation in the music classroom.
Elementary Children’s Tonal Awareness as Related to Perception of Tonal Dissonance
Authors: Norris Charles E.
Published: January 2013

This study investigated children’s tonal awareness by measuring their abilities to detect dissonance in major tonality using the author-created Tonal Dissonance Detection Test. A two-way analysis of variance of 312 elementary school subjects’ Tonal Dissonance Detection Test scores revealed that first- and second-graders’ dissonance detection abilities were significantly weaker than those of their third- to sixth-grade counterparts. Subsequent analysis revealed neither a significant gender effect nor interaction between grade level and gender. Findings are consistent with related study of the perception of tonality and tonal expectancies in children and adults. Given the homogeneity of the sample, the longevity of the music instructor, the school’s sequential Kodály-based curriculum, and conclusions of prior research, discussion considered the impact of musical instruction and musical development on the ability to perceive tonality. The author suggested the two aforementioned constructs might be studied by comparing the same perceptual skills of children from both Western and non-Western cultures.
Inclusion of People with Special Needs in Choral Settings
Authors: Salvador Karen
Published: January 2013

Despite long-standing antidiscrimination laws, such as the Americans with Disabilities Act and Individuals with Disabilities Education Act, which are meant to guarantee equal access, many school and community choirs appear to be populated primarily by students with typical physical, cognitive, and behavioral abilities. The purpose of this article is to review research and professional literature on integration of individuals with significant cognitive, speech/language, physical and/or behavioral challenges into school and community choirs. Because of the small amount of literature specifically pertaining to choirs, this review also includes pertinent literature from other performance ensembles and from elementary general music classrooms. Based on this review of literature, I will identify and describe common features or approaches of successfully integrated general music, instrumental, and choral programs. Finally, I will summarize these findings specifically with regard to their utility in school and community choral settings, with the aim of illustrating how choral directors might better include singers with special needs in their choirs.
Describing Instrumental Music Teachers’ Thinking
Authors: Millican J. Si
Published: January 2013

Pedagogical content knowledge, the particular ways that teachers understand their subjects in order to instruct others, has been described and explored in the math and science education fields in some depth, yet little research exists illustrating this concept in music instruction. I used a descriptive approach to explore expert beginning band teachers’ thinking as they viewed videotaped performances of sixth-grade instrumental music students in their first year of instruction. I categorized the expert teachers’ comments using models of pedagogical content knowledge from previous research in other subject areas in order to understand how music teachers use these skills. Teachers in the study each demonstrated a clear mental image of what they wanted to see and hear in student performances, and each used modeling, comparison, and questioning techniques to develop awareness skills in their students. The findings have implications in teacher education and teacher development in music.
Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas
Authors: Yang Chunzhang , Sun Michael G. , Matro Joey , Huynh Thanh T. , Rahimpour Shervin , Prchal Josef T. , Lechan Ronald , Lonser Russell , Pacak Karel , Zhuang Zhengping
Published: January 2013

Key Points

Newly identified mutations in HIF2A result in polycythemia and neuroendocrine tumors. Disruption of the hydroxylation domain in HIF-2α results in protein stabilization, pseudohypoxia, and tumorigenesis.
Triptans in prevention of menstrual migraine: a systematic review with meta-analysis
Authors: Hu Yong , Guan Xiaofei , Fan Lin , Jin Lingjing
Published: January 2013

Randomized clinical trials (RCT) assessing the efficacy and tolerability of triptans compared with placebo as short-term prophylaxis of menstrual migraine (MM) were systematically reviewed in this study. Triptans, which interfere with the pathogenesis of migraine and are effective in relieving associated neurovegetative symptoms, have been extensively proposed for prevention of menstrual migraine attacks. We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized, double-blind, placebo-controlled trials on triptans for MM until 1 Oct, 2012. A total of six RCTs were identified. Two authors independently assessed trial’s quality and extracted data. Numbers of participants free from MM per perimenstrual period (PMP), requiring rescue medication, suffering from headache-associated symptoms and experiencing adverse events in treatment and control groups were used to calculate relative risk (RR) and number needed to treat (NNT) with their corresponding 95% confidence interval (CI). A total of 633 participants received frovatriptan 2.5 mg QD, 584 received frovatriptan 2.5 mg BID, 392 received naratriptan 1 mg BID, 70 received naratriptan 2.5 mg BID, 80 received zolmitriptan 2.5 mg BID, 83 received zolmitriptan 2.5 mg TID and 1104 received placebo. Overall, triptans is an effective, short-term, prophylactic treatment of choice for MM. Considering MM frequency, severity and adverse events, frovatriptan 2.5 mg BID and zolmitriptan 2.5 mg TID tend to be the preferred regimens.
Reviewer acknowledgement 2012
Authors: Harris Philippa K
Published: January 2013

Contributing reviewers

The editors of BMC Developmental Biology would like to thank all our reviewers who have contributed to the journal in Volume 12 (2012).
Deep sequencing uncovers commonality in small RNA profiles between transgene-induced and naturally occurring RNA silencing of chalcone synthase-A gene in petunia
Authors: Kasai Megumi , Matsumura Hideo , Yoshida Kentaro , Terauchi Ryohei , Taneda Akito , Kanazawa Akira
Published: January 2013

Background

Introduction of a transgene that transcribes RNA homologous to an endogenous gene in the plant genome can induce silencing of both genes, a phenomenon termed cosuppression. Cosuppression was first discovered in transgenic petunia plants transformed with theCHS-Agene encoding chalcone synthase, in which nonpigmented sectors in flowers or completely white flowers are produced. Some of the flower-color patterns observed in transgenic petunias havingCHS-Acosuppression resemble those in existing nontransgenic varieties. Although the mechanism by which white sectors are generated in nontransgenic petunia is known to be due to RNA silencing of theCHS-Agene as in cosuppression, whether the same trigger(s) and/or pattern of RNA degradation are involved in these phenomena has not been known. Here, we addressed this question using deep-sequencing and bioinformatic analyses of small RNAs.

Results

We analyzed short interfering RNAs (siRNAs) produced in nonpigmented sectors of petal tissues in transgenic petunia plants that haveCHS-Acosuppression and a nontransgenic petunia variety Red Star, that has naturally occurringCHS-ARNA silencing. In both silencing systems, 21-nt and 22-nt siRNAs were the most and the second-most abundant size classes, respectively.CHS-AsiRNA production was confined to exon 2, indicating that RNA degradation through the RNA silencing pathway occurred in this exon. Common siRNAs were detected in cosuppression and naturally occurring RNA silencing, and their ranks based on the number of siRNAs in these plants were correlated with each other. Noticeably, highly abundant siRNAs were common in these systems. Phased siRNAs were detected in multiple phases at multiple sites, and some of the ends of the regions that produced phased siRNAs were conserved.

Conclusions

The features of siRNA production found to be common to cosuppression and naturally occurring silencing of theCHS-Agene indicate mechanistic similarities between these silencing systems especially in the biosynthetic processes of siRNAs including cleavage ofCHS-Atranscripts and subsequent production of secondary siRNAs in exon 2. The data also suggest that these events occurred at multiple sites, which can be a feature of these silencing phenomena.
Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM) in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis
Authors: Minami Hitomi , Yamaguchi Naoyuki , Matsushima Kayoko , Akazawa Yuko , Ohnita Ken , Takeshima Fuminao , Nakayama Toshiyuki , Hayashi Tomayoshi , Inoue Haruhiro , Nakao Kazuhiko , Isomoto Hajime
Published: January 2013

Background

Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated.

Methods

This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM.

Results

POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p<0.05) and manometric pressure studies (mean lower esophageal sphincter pressure), before 82.7 vs. after 22.9 mmHg, p<0.05) showed substantial improvement following POEM. The average numbers of esophageal epithelial nuclei before and after POEM on endocytoscopic images were 128.0 and 78.0, respectively (p<0.05). The mean Ki-67-positive ratio was 26.0 (median 25.4, range, 10.3-33.2) before and 20.7 (median 20.0, 13.1-29.9; p=0.07) after POEM, and the mean p53-positive ratio was 2.35 (median 2.61, 0.32-4.23) before and 0.97 (median 1.49, 0.32-1.56; p<0.05) after POEM. A significant positive correlation was seen between the number of nuclei and the Ki-67-positive ratio (p<0.05).

Conclusions

POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation.
A cross sectional study of HPV type prevalence according to age and cytology
Authors: Argyri Elena , Papaspyridakos Stefanos , Tsimplaki Elpida , Michala Lina , Myriokefalitaki Evangelia , Papassideri Issidora , Daskalopoulou Dimitra , Tsiaoussi Ioanna , Magiakos George , Panotopoulou Efstathia
Published: January 2013

Background

A cross sectional study to investigate HPV prevalence according to age and cytology.

Methods

Women presenting to a gynaecological outpatient clinic for a Pap smear test were included in the study (n=3177). All women had cervical cytology and HPV testing.

Results

Overall prevalence of any 24 HPV type analysed was 33.1% (95% CI 31.5% to 34.7%) and HPV 16 and HPV 42 were the most frequent (6.7% (95% CI 5.8% to 7.6%), 6.8% (95% CI 5.9% to 7.6%)), in total samples. Multiple HPV infection rate was 12.9% (95% CI 11.8% to 14.1%). High risk HPV (hrHPV) types were present in 27.4% (95% CI 25.8% to 28.9%) of the samples.

HPV prevalence was highest among 14 to 19 y.o (46.6% (95% CI 40.7%-52.4%)) and second highest among 30–34 y.o. (39.7%, 95% CI 35.4%–44%). HPV 16 was highest among 20–24 (9.0% (95% CI 6.4%–11.6%)) and second highest among 50 to 54 y.o. (6.3% (95% CI 2.9% to 9.8%).

In Low-grade Squamous Intraepithelial Lesions (LgSIL) cytology samples, the most frequently detected hrHPV types were: 16 (14.5% (95% CI 12.1% to 16.9%)), 51 (13.0% (95% CI 10.7% to 15.3%)) and 53 (9.1% (95% CI 7.2% to 11.1%)) and in High-grade Squamous Intraepithelial Lesions (HgSIL) were: HPV 16 (37.2% (95% CI 26.5% to 47.9%)), HPV 51 (17.9% (95% CI 9.4% to 26.5%)) and HPV 18 (12.8% (95% CI 5.4% to 20.2%)).

Conclusions

In the population studied, HPV 16 and 51 were the most frequent detected hrHPV types. HPV positivity, hrHPV and multiple HPV types infections were higher in young women, while HPV prevalence declined with increasing age and presented two peaks a higher (14–19 y.o.) and a lower one (30–34 y.o.) These results may contribute to the creation of a national screening programme.
Disparities in attendance at diabetes self-management education programs after diagnosis in Ontario, Canada: a cohort study
Authors: Cauch-Dudek Karen , Victor J Charles , Sigmond Marianne , Shah Baiju R
Published: January 2013

Background

Patients newly-diagnosed with diabetes require self-management education to help them understand and manage the disease. The goals of the study were to determine the frequency of diabetes self-management education program utilization by newly-diagnosed patients, and to evaluate whether there were any demographic or clinical disparities in utilization.

Methods

Using population-level health care data, all 46,553 adults who were diagnosed with any type of non-gestational diabetes in Ontario, Canada between January and June 2006 were identified. They were linked with a diabetes self-management education program registry to identify those who attended within 6 months of diagnosis. The demographic and clinical characteristics of attendees and non-attendees were compared.

Results

A total of 9,568 (20.6%) patients attended a diabetes self-management education program within 6 months of diagnosis. Younger age, increasing socioeconomic status, and the absence of mental health conditions or other medical comorbidity were associated with attendance. Patients living in rural areas, where access to physicians may be limited, were markedly more likely to attend. Recent immigrants were 40% less likely to attend self-management education programs than longer-term immigrants or nonimmigrants.

Conclusion

Only one in five newly-diagnosed diabetes patients attended a diabetes self-management education program. Demographic and clinical disparities in utilization persisted despite a publicly-funded health care system where patients could access these services without direct charges. Primary care providers and education programs must ensure that more newly-diagnosed diabetes patients receive self-management education, particularly those who are older, poorer, sicker, or recent immigrants.
Cytoplasmic free Ca2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes
Authors: Glushakova Svetlana , Lizunov Vladimir , Blank Paul S , Melikov Kamran , Humphrey Glen , Zimmerberg Joshua
Published: January 2013

Background

Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca2+ in infected erythrocytes during the multistep egress programme of malaria parasites.

Methods

Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca2+ homeostasis on the egress programme.

Results

A steady increase in cytoplasmic free Ca2+ is found to precede parasite egress. This increase is independent of extracellular Ca2+ for at least the last two hours of the cycle, but is dependent upon Ca2+ release from internal stores. Intracellular BAPTA chelation of Ca2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca2+-ATPase accelerate parasite egress, indicating that Ca2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell.

Conclusions

The parasite egress programme requires intracellular free Ca2+ for egress initiation, vacuole swelling, and host cell cytoskeleton digestion. The evidence that parasitophorous vacuole swelling, a stage of unaffected egress, is dependent upon a rise in intracellular Ca2+ suggests a mechanism for ionophore-inducible egress and a new target for Ca2+ in the programme liberating parasites from the host cell. A regulatory pathway for egress that depends upon increases in intracellular free Ca2+ is proposed.
Utilization of a population health survey in policy and practice: a case study
Authors: Laws Rachel , King Lesley , Hardy Louise L , Milat Andrew , Rissel Chris , Newson Robyn , Rychetnik Lucie , Bauman Adrian E
Published: January 2013

Background

There is growing interest by funding bodies and researchers in assessing the impact of research on real world policy and practice. Population health monitoring surveys provide an important source of data on the prevalence and patterns of health problems, but few empirical studies have explored if and how such data is used to influence policy or practice decisions. Here we provide a case study analysis of how the findings from an Australian population monitoring survey series of children’s weight and weight-related behaviors (Schools Physical Activity and Nutrition Survey (SPANS)) have been used, and the key facilitators and barriers to their utilization.

Methods

Data collection included semi-structured interviews with the chief investigators (n = 3) and end-users (n = 9) of SPANS data to explore if, how and under what circumstances the survey findings had been used, bibliometric analysis and verification using documentary evidence. Data analysis involved thematic coding of interview data and triangulation with other data sources to produce case summaries of policy and practice impacts for each of the three survey years (1997, 2004, 2010). Case summaries were then reviewed and discussed by the authors to distil key themes on if, how and why the SPANS findings had been used to guide policy and practice.

Results

We found that the survey findings were used for agenda setting (raising awareness of issues), identifying areas and target groups for interventions, informing new policies, and supporting and justifying existing policies and programs across a range of sectors. Reported factors influencing use of the findings were: i) the perceived credibility of survey findings; ii) dissemination strategies used; and, iii) a range of contextual factors.

Conclusions

Using a novel approach, our case study provides important new insights into how and under what circumstances population health monitoring data can be used to influence real world policy and practice. The findings highlight the importance of population monitoring programs being conducted by independent credible agencies, researchers engaging end-users from the inception of survey programs and utilizing existing policy networks and structures, and using a range of strategies to disseminate the findings that go beyond traditional peer review publications.
Hodgkin’s lymphoma emerging radiation treatment techniques: trade-offs between late radio-induced toxicities and secondary malignant neoplasms
Authors: Cella Laura , Conson Manuel , Pressello Maria Cristina , Molinelli Silvia , Schneider Uwe , Donato Vittorio , Orecchia Roberto , Salvatore Marco , Pacelli Roberto
Published: January 2013

Background

Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin’s lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model.

Methods

Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses.

Results

With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs’ dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique.

Conclusions

Our model–based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs’ risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy.
Characterisation of fibroblast-like synoviocytes from a murine model of joint inflammation
Authors: Hardy Rowan S , Hülso Claudia , Liu Yingling , Gasparini Sylvia J , Fong-Yee Colette , Tu Jinwen , Stoner Shihani , Stewart Paul M , Raza Karim , Cooper Mark S , Seibel Markus J , Zhou Hong
Published: January 2013

Introduction

Fibroblast-like synoviocytes (FLS) play a central role in defining the stromal environment in inflammatory joint diseases. Despite a growing use of FLS isolated from murine inflammatory models, a detailed characterisation of these cells has not been performed.

Methods

In this study, FLS were isolated from inflamed joints of mice expressing both the T cell receptor transgene KRN and the MHC class II molecule Ag7 (K/BxN mice) and their purity in culture determined by immunofluorescence and real-time reverse transcription polymerase chain reaction (real-time RT-PCR). Basal expression of proinflammatory genes was determined by real-time RT-PCR. Secreted interleukin 6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA), and its regulation by tumor necrosis factor-alpha (TNF-α and corticosterone (the major glucocorticoid in rodents) measured relative to other mesenchymal cell populations.

Results

Purity of FLS culture was identified by positive expression of fibronectin, prolyl 4-hydroxylase, cluster of differentiation 90.2 (CD90.2) and 248 (CD248) in greater than 98% of the population. Cultured FLS were able to migrate and invade through matrigel, a process enhanced in the presence of TNF-α. FLS isolated from K/BxN mice possessed significantly greater basal expression of the inflammatory markers IL-6, chemokine ligand 2 (CCL-2) and vascular cell adhesion molecule 1 (VCAM-1) when compared to FLS isolated from non-inflamed tissue (IL-6, 3.6 fold; CCL-2, 11.2 fold; VCAM-1, 9 fold; P < 0.05). This elevated expression was abrogated in the presence of corticosterone at 100 nmol/l. TNF-α significantly increased expression of all inflammatory markers to a much greater degree in K/BxN FLS relative to other mesenchymal cell lines (K/BxN; IL-6, 40.8 fold; CCL-2, 1343.2 fold; VCAM-1, 17.8 fold; ICAM-1, 13.8 fold; P < 0.05), with secreted IL-6 mirroring these results (K/BxN; con, 169 ± 29.7 versus TNF-α, 923 ± 378.8 pg/ml/1 × 105 cells; P < 0.05). Dose response experiments confirmed effective concentrations between 10 and 100 nmol/l for corticosterone and 1 and 10 ng/ml for TNF-α, whilst inflammatory gene expression in FLS was shown to be stable between passages four and seven.

Conclusions

This study has established a well characterised set of key inflammatory genes for in vitro FLS culture, isolated from K/BxN mice and non-inflamed wild-type controls. Their response to both pro- and anti-inflammatory signalling has been assessed and shown to strongly resemble that which is seen in human FLS culture. Additionally, this study provides guidelines for the effective characterisation, duration and treatment of murine FLS culture.
Comparative analysis of tandem repeats from hundreds of species reveals unique insights into centromere evolution
Authors: Melters Daniël P , Bradnam Keith R , Young Hugh A , Telis Natalie , May Michael R , Ruby J Graham , Sebra Robert , Peluso Paul , Eid John , Rank David , Garcia José Fernando , DeRisi Joseph L , Smith Timothy , Tobias Christian , Ross-Ibarra Jeffrey , Korf Ian , Chan Simon WL
Published: January 2013

Background

Centromeres are essential for chromosome segregation, yet their DNA sequences evolve rapidly. In most animals and plants that have been studied, centromeres contain megabase-scale arrays of tandem repeats. Despite their importance, very little is known about the degree to which centromere tandem repeats share common properties between different species across different phyla. We used bioinformatic methods to identify high-copy tandem repeats from 282 species using publicly available genomic sequence and our own data.

Results

Our methods are compatible with all current sequencing technologies. Long Pacific Biosciences sequence reads allowed us to find tandem repeat monomers up to 1,419 bp. We assumed that the most abundant tandem repeat is the centromere DNA, which was true for most species whose centromeres have been previously characterized, suggesting this is a general property of genomes. High-copy centromere tandem repeats were found in almost all animal and plant genomes, but repeat monomers were highly variable in sequence composition and length. Furthermore, phylogenetic analysis of sequence homology showed little evidence of sequence conservation beyond approximately 50 million years of divergence. We find that despite an overall lack of sequence conservation, centromere tandem repeats from diverse species showed similar modes of evolution.

Conclusions

While centromere position in most eukaryotes is epigenetically determined, our results indicate that tandem repeats are highly prevalent at centromeres of both animal and plant genomes. This suggests a functional role for such repeats, perhaps in promoting concerted evolution of centromere DNA across chromosomes.
Reduction of indoxyl sulfate by AST-120 attenuates monocyte inflammation related to chronic kidney disease
Authors: Ito Shunsuke , Higuchi Yusuke , Yagi Yoko , Nishijima Fuyuhiko , Yamato Hideyuki , Ishii Hideto , Osaka Mizuko , Yoshida Masayuki
Published: January 2013

Indoxyl sulfate induced Mac-1 expression and ROS production via p38 MAPK- and NAD(P)H oxidase-dependent pathways.

Accelerated cardiovascular disease is a frequent complication of CKD. Monocyte-mediated inflammation and adhesion of monocytes to vascular endothelium are key events in atherogenesis. An oral adsorbent, AST-120, retards renal function deterioration by lowering IS, which is known to accumulate in CKD patients. However, the effect of AST-120 on CKD-related monocyte activation is unknown. We aimed to determine whether AST-120 improves monocyte-mediated inflammation through IS reduction. Flow cytometric analysis showed that Mac-1 expression and ROS production were significantly higher in peripheral blood monocytes of subtotal Nx CKD mice than in sham-operated mice. AST-120 treatment significantly decreased Mac-1 expression and ROS production in CKD model mice. Furthermore, administration of IS induced monocyte-mediated inflammation and ROS generation. In vitro studies indicated that IS dose-dependently increased THP-1 monocytic cell adhesion to IL-1β-activated HUVECs under physiological flow conditions. IS also induced monocyte-mediated inflammation and ROS production in THP-1 cells. Phosphorylation of p38 MAPK and membrane translocation of NAD(P)H oxidase subunit p47phox in THP-1 cells were induced by IS. Both SB203580 (p38 MAPK inhibitor) and apocynin [NAD(P)H oxidase inhibitor] reduced THP-1 cell adhesion to HUVECs. Apocynin also inhibited IS-induced ROS production in THP-1 cells. IS induced monocyte-driven inflammation through NAD(P)H oxidase- and p38 MAPK-dependent pathways in monocytes. The main finding of this study was that AST-120 inhibited monocyte activation by reducing IS in vivo. This provides new insights on how AST-120 attenuates the progression of atherosclerosis in CKD.
Cooperation of Hydrogen-Bond and Charge-Transfer Interactions in Molecular Complexes in the Solid State
Authors: Morita Yasushi , Murata Tsuyoshi , Nakasuji Kazuhiro
Published: January 2013

Our recent studies for the development of conducting charge-transfer complexes with well-defined assembled structures based on the cooperation of hydrogen-bond and charge-transfer interactions are described. We have designed and synthesized hydrogen-bonded charge-transfer complexes based on (1) tetrathiafulvalene derivatives having nucleobases, aminobenzo and imidazole moieties, and (2) tetracyanoquinodimethane radical anion salts with hydrogen-bond-functionalized phenalenyl and protonated oligo(imidazole) cations. The directional and site-selective hydrogen-bonds formed various supramolecular network structures, constructing segregated columns as the conduction path. Furthermore, the high polarity of hydrogen-bonds caused strong donor–acceptor or cation–anion electrostatic interactions modulating the ionicity of component molecules and the electronic structure of conduction columns. Such electronic modulation effects in addition to controlling the molecular arrangement realized the first purely organic molecular metal based on a hydrogen-bonded charge-transfer complex in the p-chloranil complex of an imidazole-functionalized tetrathiafulvalene derivative. The proton-donating/accepting ability of the hydrogen-bonding sites afforded the simultaneous proton- and charge-transfer complexes, demonstrating an important prompt for the realization of cooperative proton–electron-transfer systems.
Sudden death in advanced abdominal pregnancy: a case report and discussion of the related medicolegal issues
Authors: Pradhan M , Sreenivas M , Singh Bajrang , Behera C , Dikshit P C
Published: January 2013

We report sudden unexpected death in a 35-year-old woman with pregnancy of seven months duration. There was an allegation by the parents of the woman that she was subjected to an assault prior to death. Autopsy examination showed an abdominal pregnancy with a dead fetus, ruptured gestational sac, massive haemorrhage and secondary placental attachment. During her antenatal check-ups, she had persistently complained of abdominal pain and loose stools, but the diagnosis of abdominal pregnancy was missed clinically and on ultrasound scan. In this paper we discuss the diagnostic difficulties and medicolegal issues in such cases.
Surface finish of the Exeter Trauma Stem
Authors: Petheram T. G. , Bone M. , Joyce T. J. , Serrano-Pedraza I. , Reed M. R. , Partington P. F.
Published: January 2013

Recent guidance recommends the use of a well-proven cemented femoral stem for hemiarthroplasty in the management of fractures of the femoral neck, and the Exeter Trauma Stem (ETS) has been suggested as an example of such an implant. The design of this stem was based on the well-proven Exeter Total Hip Replacement stem (ETHRS). This study assessed the surface finish of the ETS in comparison with the ETHRS. Two ETSs and two ETHRSs were examined using a profilometer with a precision of 1 nm and compared with an explanted Exeter Matt stem. The mean roughness average (RA) of the ETSs was approximately ten times higher than that of the ETHRSs (0.235 μm (0.095 to 0.452) versus 0.025 μm (0.011 to 0.059); p < 0.001). The historical Exeter Matt stem roughness measured a mean RA of 0.973 μm (0.658 to 1.159). The change of the polished Exeter stem to a matt surface finish in 1976 resulted in a high stem failure rate. We do not yet know whether the surface differences between ETS and ETHRS will be clinically significant. We propose the inclusion of hemiarthroplasty stems in national joint registries.

Cite this article: Bone Joint J 2013;95-B:173–6.
Evaluation of the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in a mini-pig spinal anterior interbody fusion model
Authors: Hwang C. J. , Lee J. H. , Baek H-R. , Chang B-S. , Lee C-K.
Published: January 2013

We evaluated the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) in a mini-pig model of spinal anterior interbody fusion. A total of 14 male mini-pigs underwent three-level anterior lumbar interbody fusion using polyether etherketone (PEEK) cages containing porous hydroxyapatite (HA). Four groups of cages were prepared: 1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks after surgery the mini-pigs were killed and the specimens were evaluated by gross inspection and manual palpation, radiological evaluation including plain radiographs and micro-CT scans, and histological analysis. Rates of fusion within PEEK cages and overall union rates were calculated, and bone formation outside vertebrae was evaluated. One animal died post-operatively and was excluded, and one section was lost and also excluded, leaving 38 sites for assessment. This rate of fusion within cages was 30.0% (three of ten) in the control group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in the 800 μg E-BMP-2 group. Fusion rate was significantly increased by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p = 0.046). In a mini-pig spinal anterior interbody fusion model using porous HA as a carrier, the implantation of E-BMP-2-loaded PEEK cages improved the fusion rate compared with PEEK cages alone, an effect that was significantly increased with increasing E-BMP-2 dosage.

Cite this article: Bone Joint J 2013;95-B:217–23.
Risk factors for overgrowth after flexible intramedullary nailing for fractures of the femoral shaft in children
Authors: Park S-S. , Noh H. , Kam M.
Published: January 2013

We analysed retrospectively the risk factors leading to femoral overgrowth after flexible intramedullary nailing in 43 children (mean age 7.1 years (3.6 to 12.0)) with fractures of the shaft of the femur. We reviewed their demographic data, mechanism of injury, associated injuries, the type and location of the fractures, the nail–canal diameter (NCD) ratios and femoral overgrowth at a mean follow-up of 40.7 months (25.2 to 92.7). At that time, the children were divided into two groups, those with femoral overgrowth of < 1 cm (Group 1), and those with overgrowth of ≥ 1 cm (Group 2). The mean femoral overgrowth of all patients was 0.6 cm at final follow-up. Overgrowth of ≥ 1 cm was noted in 11 children (25.6%). The NCD ratio was significantly lower in Group 2 than in Group 1, with an odds ratio of 30.0 (p = 0.003).

We believe that a low NCD ratio is an indicator of an unstable configuration with flexible intramedullary nailing, and have identified an association between a low NCD ratio and femoral overgrowth resulting in leg-length discrepancy after flexible intramedullary nailing in paediatric femoral shaft fractures.

Cite this article: Bone Joint J 2013;95-B:254–8.
A new mechanism of injury in ankylosing spondylitis
Authors: Samartzis D. , Modi H. N. , Cheung K. M. C. , Luk K. D. K.
Published: January 2013

Ankylosing spondylitis (AS) is a progressive multisystem chronic inflammatory disorder. The hallmark of this pathological process is a progressive fusion of the zygapophyseal joints and disc spaces of the axial skeleton, leading to a rigid kyphotic deformity and positive sagittal balance. The ankylosed spine is unable to accommodate normal mechanical forces, rendering it brittle and susceptible to injury. Traumatic hyperextension injury of the cervical spine leading to atlantoaxial subluxation (AAS) in AS patients can often be fatal. We report a non-traumatic mechanism of injury in AS progressing to AAS attributable to persistent hyperextension, which resulted in fatal migration of C2 through the foramen magnum.

Cite this article: Bone Joint J 2013;95-B:206–9.
Cementless fixation in Oxford unicompartmental knee replacement
Authors: Liddle A. D. , Pandit H. , O’Brien S. , Doran E. , Penny I. D. , Hooper G. J. , Burn P. J. , Dodd C. A. F. , Beverland D. E. , Maxwell A. R. , Murray D. W.
Published: January 2013

The Cementless Oxford Unicompartmental Knee Replacement (OUKR) was developed to address problems related to cementation, and has been demonstrated in a randomised study to have similar clinical outcomes with fewer radiolucencies than observed with the cemented device. However, before its widespread use it is necessary to clarify contraindications and assess the complications. This requires a larger study than any previously published.

We present a prospective multicentre series of 1000 cementless OUKRs in 881 patients at a minimum follow-up of one year. All patients had radiological assessment aligned to the bone–implant interfaces and clinical scores. Analysis was performed at a mean of 38.2 months (19 to 88) following surgery. A total of 17 patients died (comprising 19 knees (1.9%)), none as a result of surgery; there were no tibial or femoral loosenings. A total of 19 knees (1.9%) had significant implant-related complications or required revision. Implant survival at six years was 97.2%, and there was a partial radiolucency at the bone–implant interface in 72 knees (8.9%), with no complete radiolucencies. There was no significant increase in complication rate compared with cemented fixation (p = 0.87), and no specific contraindications to cementless fixation were identified.

Cementless OUKR appears to be safe and reproducible in patients with end-stage anteromedial osteoarthritis of the knee, with radiological evidence of improved fixation compared with previous reports using cemented fixation.

Cite this article: Bone Joint J 2013;95-B:181–7.
Prevalence of radiographic findings associated with hip dysplasia in a population-based cohort of 2081 19-year-old Norwegians
Authors: Engesæter I. Ø. , Laborie L. B. , Lehmann T. G. , Fevang J. M. , Lie S. A. , Engesæter L. B. , Rosendahl K.
Published: January 2013

In Norway total joint replacement after hip dysplasia is reported more commonly than in neighbouring countries, implying a higher prevalence of the condition. We report on the prevalence of radiological features associated with hip dysplasia in a population of 2081 19-year-old Norwegians. The radiological measurements used to define hip dysplasia were Wiberg’s centre-edge (CE) angle at thresholds of < 20° and < 25°, femoral head extrusion index <  75%, Sharp’s angle > 45°, an acetabular depth to width ratio < 250 and the sourcil shape assessed subjectively. The whole cohort underwent clinical examination of their range of hip movement, body mass index (BMI), and Beighton hypermobility score, and were asked to complete the EuroQol (EQ-5D) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The prevalence of hip dysplasia in the cohort varied from 1.7% to 20% depending on the radiological marker used. A Wiberg’s CE angle <  20° was seen in 3.3% of the cohort: 4.3% in women and 2.4% in men. We found no association between subjects with multiple radiological signs indicative of dysplasia and BMI, Beighton score, EQ-5D or WOMAC. Although there appears to be a high prevalence of hip dysplasia among 19-year-old Norwegians, this is dependent on the radiological parameters applied.

Cite this article: Bone Joint J 2013;95-B:279–85.
Exam Corner – February 2013
Authors: Khanduja V.
Published: January 2013

The FRCS (Tr & Orth) examination has three components: MCQs, Vivas and Clinical Examination. The Vivas are further divided into four sections comprising Basic Science, Adult Pathology, Hands and Children’s Orthopaedics and Trauma. The Clinical Examination section is divided into Upper and Lower limb cases. The aim of this section in the Journal is to focus specifically on the trainees preparing for the exam and to cater to all the sections of the exam. The vision is to complete the cycle of all relevant exam topics (as per the syllabus) in four years.
MicroCT versus sTSLIM 3D Imaging of the Mouse Cochlea
Authors: Buytaert Jan A.N. , Johnson Shane B. , Dierick Manuel , Salih Wasil H.M. , Santi Peter A.
Published: January 2013

We made a qualitative and quantitative comparison between a state-of-the-art implementation of micro-Computed Tomography (microCT) and the scanning Thin-Sheet Laser Imaging Microscopy (sTSLIM) method, applied to mouse cochleae. Both imaging methods are non-destructive and perform optical sectioning, respectively, with X-rays and laser light. MicroCT can be used on fresh or fixed tissue samples and is primarily designed to image bone rather than soft tissues. It requires complex back-projection algorithms to produce a two-dimensional image, and it is an expensive instrument. sTSLIM requires that a specimen be chemically fixed, decalcified, and cleared; but it produces high-resolution images of soft and bony tissues with minimum image postprocessing and is less expensive than microCT. In this article, we discuss the merits and disadvantages of each method individually and when combined.
Where One Hand Meets the Other: Limb-Specific and Action-Dependent Movement Plans Decoded from Preparatory Signals in Single Human Frontoparietal Brain Areas
Authors: Gallivan Jason P. , McLean D. Adam , Flanagan J. Randall , Culham Jody C.
Published: January 2013

Planning object-directed hand actions requires successful integration of the movement goal with the acting limb. Exactly where and how this sensorimotor integration occurs in the brain has been studied extensively with neurophysiological recordings in nonhuman primates, yet to date, because of limitations of non-invasive methodologies, the ability to examine the same types of planning-related signals in humans has been challenging. Here we show, using a multivoxel pattern analysis of functional MRI (fMRI) data, that the preparatory activity patterns in several frontoparietal brain regions can be used to predict both the limb used and hand action performed in an upcoming movement. Participants performed an event-related delayed movement task whereby they planned and executed grasp or reach actions with either their left or right hand toward a single target object. We found that, although the majority of frontoparietal areas represented hand actions (grasping vs reaching) for the contralateral limb, several areas additionally coded hand actions for the ipsilateral limb. Notable among these were subregions within the posterior parietal cortex (PPC), dorsal premotor cortex (PMd), ventral premotor cortex, dorsolateral prefrontal cortex, presupplementary motor area, and motor cortex, a region more traditionally implicated in contralateral movement generation. Additional analyses suggest that hand actions are represented independently of the intended limb in PPC and PMd. In addition to providing a unique mapping of limb-specific and action-dependent intention-related signals across the human cortical motor system, these findings uncover a much stronger representation of the ipsilateral limb than expected from previous fMRI findings.
Bayesian Prediction and Evaluation in the Anterior Cingulate Cortex
Authors: Ide Jaime S. , Shenoy Pradeep , Yu Angela J. , Li Chiang-shan R.
Published: January 2013

The dorsal anterior cingulate cortex (dACC) has been implicated in a variety of cognitive control functions, among them the monitoring of conflict, error, and volatility, error anticipation, reward learning, and reward prediction errors. In this work, we used a Bayesian ideal observer model, which predicts trial-by-trial probabilistic expectation of stop trials and response errors in the stop-signal task, to differentiate these proposed functions quantitatively. We found that dACC hemodynamic response, as measured by functional magnetic resonance imaging, encodes both the absolute prediction error between stimulus expectation and outcome, and the signed prediction error related to response outcome. After accounting for these factors, dACC has no residual correlation with conflict or error likelihood in the stop-signal task. Consistent with recent monkey neural recording studies, and in contrast with other neuroimaging studies, our work demonstrates that dACC reports at least two different types of prediction errors, and beyond contexts that are limited to reward processing.