bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo finished 2.8 Mbp Staphylococcus aureus genome assembly from 100 bp short and long range paired-end reads
Authors: Hernandez David , Tewhey Ryan , Veyrieras Jean-Baptiste , Farinelli Laurent , Østerås Magne , François Patrice , Schrenzel Jacques
Published: October 2013

Motivation: Paired-end sequencing allows circumventing the shortness of the reads produced by second generation sequencers and is essential for de novo assembly of genomes. However, obtaining a finished genome from short reads is still an open challenge. We present an algorithm that exploits the pairing information issued from inserts of potentially any length. The method determines paths through an overlaps graph by using a constrained search tree. We also present a method that automatically determines suited overlaps cutoffs according to the contextual coverage, reducing thus the need for manual parameterization. Finally, we introduce an interactive mode that allows querying an assembly at targeted regions.

Results: We assess our methods by assembling two Staphylococcus aureus strains that were sequenced on the Illumina platform. Using 100 bp paired-end reads and minimal manual curation, we produce a finished genome sequence for the previously undescribed isolate SGH-10-168.

Availability and implementation: The presented algorithms are implemented in the standalone Edena software, freely available under the General Public License (GPLv3) at www.genomic.ch/edena.php.

Contact:  david.hernandez@genomic.ch

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Sperm competition risk generates phenotypic plasticity in ovum fertilizability
Authors: Firman Renée C. , Simmons Leigh W.
Published: October 2013

Theory predicts that sperm competition will generate sexual conflict that favours increased ovum defences against polyspermy. A recent study on house mice has shown that ovum resistance to fertilization coevolves in response to increased sperm fertilizing capacity. However, the capacity for the female gamete to adjust its fertilizability as a strategic response to sperm competition risk has never, to our knowledge, been studied. We sourced house mice (Mus domesticus) from natural populations that differ in the level of sperm competition and sperm fertilizing capacity, and manipulated the social experience of females during their sexual development to simulate conditions of either a future ‘risk’ or ‘no risk’ of sperm competition. Consistent with coevolutionary predictions, we found lower fertilization rates in ova produced by females from a high sperm competition population compared with ova from a low sperm competition population, indicating that these populations are divergent in the fertilizability of their ova. More importantly, females exposed to a ‘risk’ of sperm competition produced ova that had greater resistance to fertilization than ova produced by females reared in an environment with ‘no risk’. Consequently, we show that variation in sperm competition risk during development generates phenotypic plasticity in ova fertilizability, which allows females to prepare for prevailing conditions during their reproductive life.
Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential
Authors: Anand Sanjeev K. , Gaba Amit , Singh Jaswant , Tikoo Suresh K.
Published: October 2013

Viruses modulate the functions of mitochondria by translocating viral proteins to the mitochondria. Subcellular fractionation and sensitivity to proteinase K/Triton X-100 treatment of mitochondrial fractions of bovine adenovirus (BAdV)-3-infected/transfected cells suggested that core protein pVII localizes to the mitochondria and contains a functional mitochondrial localization signal. Moreover, mitochondrial localization of BAdV-3 pVII appears to help in the retention of mitochondrial Ca2+, inducing a significant increase in the levels of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant effect on the levels of cytoplasmic Ca2+ and reactive oxygen species production in the transfected cells. Consistent with these results, expression of pVII in transfected cells treated with staurosporine decreased significantly the activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by increasing mitochondrial Ca2+ and ATP production.
Virus isolate from carp: genetic characterization reveals a novel picornavirus with two aphthovirus 2A-like sequences
Authors: Lange Jeannette , Groth Marco , Fichtner Dieter , Granzow Harald , Keller Barbara , Walther Mario , Platzer Matthias , Sauerbrei Andreas , Zell Roland
Published: October 2013

Picornaviruses have been isolated from a variety of hosts, mainly mammals and birds. Here, we describe the sequence analysis of carp picornavirus 1 (CPV-1) F37/06 that was isolated from an organ pool (heart, brain, liver) of a common carp (Cyprinus carpio). This carp perished after an accidental discharge of liquid manure into a fish pond and presented without obvious clinical symptoms. Experimental intraperitoneal infection of young carp with CPV-1 revealed no clinical signs, but the virus was re-isolated from various organs. Sequence analysis of almost the complete genome (7632 nt excluding the poly-A tract) revealed a novel picornavirus clade. In phylogenetic trees, the polymerase sequence clusters with parechoviruses, duck hepatitis A virus, eel picornavirus and aquamavirus A. The ORF includes 6807 nt and encodes a polyprotein of 2269 amino acids. CPV-1 has a genome layout like that of picornaviruses except for the presence of two aphthovirus 2A-like NPGP sequence motifs: VPg+5′UTR[1AB-1C-1D-2A1npgp/2A2npgp-2B-2CATPase/3A-3BVPg-3Cpro-3Dpol]3′UTR-poly-A. 2A1npgp and 2A2npgp are separated by 133 amino acids. The proteins 2A2npgp, 2B, 3A and 3BVPg have no significant similarity to the corresponding proteins of other picornaviruses. Amino acid identities of the orthologous proteins P1, 2C, 3Cpro and 3Dpol range from 16.4 to 40.8 % in the eel picornavirus/CPV-1 comparison. 3Dpol shows the closest similarity to eel picornavirus, with an amino acid identity of 40.8 %, followed by human parechovirus (36.5 %), duck hepatitis A virus (32.7 %) and swine pasivirus (29.3 %). Both the unique genome organization and low sequence similarity support the assignment of CPV-1 to a novel picornavirus species within a novel genus.
Evidence of subclinical prion disease in aged mice following exposure to bovine spongiform encephalopathy
Authors: Brown Karen L. , Mabbott Neil A.
Published: October 2013

The occurrence of variant Creutzfeldt–Jakob (vCJD) disease in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has been identified predominantly in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure, many prions replicate within the lymphoid tissues before infecting the central nervous system. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the ‘species barrier’, which is dependent on several factors, including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (6–8 weeks old) and aged (600 days old) mice injected with primary BSE brain homogenate. We showed that prion pathogenesis was impaired dramatically in aged mice when compared with young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE brain homogenate, in the absence of clinical signs of prion disease, has important implications for human health.
A Two-Hybrid-Receptor Assay Demonstrates Heteromer Formation as Switch-On for Plant Immune Receptors
Authors: Albert Markus , Jehle Anna Kristina , Fürst Ursula , Chinchilla Delphine , Boller Thomas , Felix Georg
Published: October 2013

Receptor kinases sense extracellular signals and trigger intracellular signaling and physiological responses. However, how does signal binding to the extracellular domain activate the cytoplasmic kinase domain? Activation of the plant immunoreceptor Flagellin sensing2 (FLS2) by its bacterial ligand flagellin or the peptide-epitope flg22 coincides with rapid complex formation with a second receptor kinase termed brassinosteroid receptor1 associated kinase1 (BAK1). Here, we show that the receptor pair of FLS2 and BAK1 is also functional when the roles of the complex partners are reversed by swapping their cytosolic domains. This reciprocal constellation prevents interference by redundant partners that can partially substitute for BAK1 and demonstrates that formation of the heteromeric complex is the molecular switch for transmembrane signaling. A similar approach with swaps between the Elongation factor-Tu receptor and BAK1 also resulted in a functional receptor/coreceptor pair, suggesting that a “two-hybrid-receptor assay” is of more general use for studying heteromeric receptor complexes.
High‐grade mucoepidermoid carcinoma of the columella successfully reconstructed using bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft after surgical resection
Authors: Nakamura Yoshiyuki , Nakamura Yasuhiro , Saito Akimasa , Fujisawa Yasuhiro , Kawachi Yasuhiro , Otsuka Fujio
Published: October 2013

Mucoepidermoid carcinoma (MEC) usually originates from the salivary glands. However, there has been no report on mucoepidermoid carcinoma of the columella. In this study, we report the case of a high‐grade MEC of the columella that was successfully reconstructed after surgical resection with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. A 66‐year‐old man presented with a nodule on the columella. Histological findings were suggestive of a high‐grade mucoepidermoid carcinoma. Wide excision was performed, and the defects of the columella and the nasal floor were reconstructed with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. The postoperative cosmetic result was good with excellent tissue texture. The reconstructed columella had an appropriate, not bulky, width as well as satisfactory height and depth. This reconstructive technique is particularly useful for correcting the large defect of the columella with nasal septum and/or nasal floor defects.
Combined measurement of multiple acute phase reactants to predict relapse of rheumatoid arthritis
Authors: Lv Fang , Song Li‐Jun , Li Xing‐Fu
Published: October 2013

Aim

Acute phase reactants (APRs), such as serum C‐reactive protein (CRP), ferritin, plasma fibrinogen and platelet count, are common biomarkers used to monitor the status of inflammatory diseases. The aim of this study was to determine whether APRs are predictive markers of relapse in rheumatoid arthritis (RA).

Method

We analyzed forty RA patients in clinical remission (disease activity score [DAS28] < 2.6; baseline [t0]) or with low disease activity (DAS28 score ≤ 3.2; t0). The pre‐existing therapeutic regimens were retained for each patient during a 4‐week study period. APRs and patient characteristics were analyzed for normality of distribution by using the Kolmogorov–Smirnov test and correlations were assessed by Pearson's or Spearman's rank correlation coefficient.

Results

APR levels were found to be significantly correlated with DAS28 score of RA, and serum CRP was the most strongly correlated APR for both the clinical remission and high disease activity groups. For all APRs, the correlation strength paralleled the increase in disease activity.

Conclusion

Measurement of multiple APRs in remission or low disease activity RA patients may predict relapse to active disease, thereby facilitating more timely clinical management and promoting efficacy of therapeutic intervention.
The Distribution of the H‐index Among Academic Emergency Physicians in the United States
Authors: DeLuca Lawrence A. , St. John Alex , Stolz Uwe , Matheson Lincoln , Simpson Allan , Denninghoff Kurt R.
Published: October 2013

Background

Hirsch's h‐index (h) attempts to measure the combined academic impact and productivity of a scientist by counting the number of publications by an author, ranked in descending order by number of citations, until the paper number equals the number of citations. This approach provides a natural number or index of the number of publications and the number of citations per publication. H was first described in physics and was demonstrated to be highly predictive of continued academic activity, including recognized measures of scientific excellence such as membership in the National Academy of Sciences and being a Nobel laureate. Citation rates, research environments, and years of experience all affect h, making any comparisons appropriate only for scientists working in the same field for a similar time period. The authors are unaware of any report describing the distribution of h among academic emergency physicians (AEPs).

Objectives

The objective was to describe the distribution of h for AEPs and to determine whether Hirsch's demonstration of the h‐index as a predictor of continued scholarly activity among physicists would also apply to AEPs.

Methods

Academic EPs were identified from lists provided on allopathic U.S. emergency medicine (EM) residency program websites. “Harzing's Publish or Perish,” a free program available on the Web that queries Google Scholar, was used to calculate h for each AEP. Agreement between raters was analyzed on a subset of 100 EPs. An analysis of the 20 EPs with the top h‐indices was performed to characterize the entire body of their scholarly work, and their h‐indices were calculated at 12 and 24 years into their careers.

Results

A total of 4,744 AEPs from 136 programs were evaluated. Nine programs did not publicly list the faculty at their institutions and were excluded. A linear weighted kappa was used to measure rater concordance, with agreement of 98.3% and κ = 0.92 (95% confidence interval [CI] = 0.861 to 0.957). The majority of AEPs had h‐indices of zero or one (59%), 85% had h‐indices less than six, 95% less than 13, and 99% less than 24. Ten percent of AEPs had h/(years in publication) of 0.5 or greater. For the top 20 EPs, the mean (± standard deviation [±SD]) h‐index increased from 7.6 (±4.6) to 23.5 (±9.4) between years 12 and 24. The mean (±SD) increase in h‐index was 15.8 (±7.6).

Conclusions

The h‐index can be used to characterize the academic productivity of AEPs. An h/year of 0.5 or greater is characteristic of the most productive EPs and represents only 10% of all AEPs. The 12‐year h‐index of top‐performing EPs was strongly related to their future academic productivity. The distribution of h among EPs may provide a means for individual investigators and academic leaders to evaluate performance and identify EPs with future success in EM research.
Near‐infrared Spectroscopy Assessment of Tissue Saturation of Oxygen in Torsed and Healthy Testes
Authors: Schoenfeld Elizabeth M. , Capraro Geoffrey A. , Blank Fidela S. J. , Coute Ryan A. , Visintainer Paul F.
Published: October 2013

Objectives

The objective was to assess whether testicular torsion is associated with low testicular tissue saturation of oxygen (StO2) as measured by transscrotal near‐infrared spectroscopy (NIRS) and to compare the differences in NIRS values between testicles of the same patient, both in patients with testicular torsion and in healthy controls.

Methods

This was an observational study of healthy controls and patients with surgically confirmed testicular torsion who were recruited from males under 30 years of age presenting to the emergency department (ED). The hypothesis was that the difference in NIRS values for the control's two testicles would be zero, and that the difference between the torsed and healthy testicles on an individual patient would not be zero. Based on animal data, the study was powered to detect an absolute difference of StO2 of 47%.

Results

The mean StO2 for the left control patients' testicles was 73.6% (95% confidence interval [CI] = 68.0% to 79.1%) and the mean StO2 for the right controls' testicles for controls was 73.6% (95% CI = 66.9% to 80.4%; n = 17). The absolute difference in NIRS StO2 for left minus right for each individual was 3.5% (95% CI = 1.8% to 5.4%), which was significantly different (p = 0.0007), and refuted the hypothesis that there was no significant difference in StO2 between left and right testes in healthy patients. In the testicular torsion group, the torsed side had a mean StO2 of 82.8% (95% CI = 68.7% to 96.9%), and the contralateral nontorsed testes had a mean of 85.8% (95% CI = 72.3% to 99.3%). The mean StO2 difference, nontorsed minus torsed was 3.0% (range = –1% to 9%, 95% CI = –2% to 8%; p = 0.174), refuting the hypothesis that torsed testes would demonstrate significantly lower values for StO2.

Conclusions

While pilot animal investigations support a potential role for transscrotal NIRS for the detection of testicular torsion, this first clinical translation of animal findings reveals that the investigated, transcutaneous, reflectance geometry NIRS device failed to demonstrate symmetric oxygenation of left and right testes in healthy controls and also failed to demonstrate depressed tissue saturation of oxygen values in patients with confirmed testicular torsion. While limited by a small sample size, other problems such as inability to calibrate depth of measurement of StO2 may have led to falsely elevated readings in patients with torsion.
When Coverage Expands: Children's Health Insurance Program as a Natural Experiment in Use of Health Care Services
Authors: Haggins Adrianne , Patrick Stephen , Demonner Sonya , Davis Matthew M.
Published: October 2013

Background

Expanding insurance coverage is designed to improve access to primary care and reduce use of emergency department (ED) services. Whether expanding coverage achieves this is of paramount importance as the United States prepares for the Affordable Care Act.

Objectives

Emergency and outpatient department use was examined after the State Children's Health Insurance Program (CHIP) coverage expansion, focusing on adolescents (a major target group for CHIP) versus young adults (not targeted). The hypothesis was that coverage would increase use of outpatient services, and ED use would decrease.

Methods

Using the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS), the years 1992–1996 were analyzed as baseline and then compared to use patterns in 1999–2009, after the CHIP launch. Primary outcomes were population‐adjusted annual visits to ED versus nonemergency outpatient settings. Interrupted time series were performed on use rates to ED and outpatient departments between adolescents (11 to 18 years old) and young adults (19 to 29 years old) in the pre‐CHIP and CHIP periods. Outpatient‐to‐ED ratios were calculated and compared across time periods. A stratified analysis by payer and sex was also performed.

Results

The mean number of outpatient adolescent visits increased by 299 visits per 1,000 persons (95% confidence interval [CI] = 140 to 457), while there was no statistically significant increase in young adult outpatient visits across time periods. There was no statistically significant change in the mean number of adolescent ED visits across time periods, while young adult ED use increased by 48 visits per 1,000 persons (95% CI = 24 to 73). The adolescent outpatient‐to‐ED ratio increased by 1.0 (95% CI = 0.49 to 1.6), while the young adults ratio decreased by 0.53 across time periods (95% CI = –0.90 to –0.16).

Conclusions

Since CHIP, adolescent non‐ED outpatient visits have increased, while ED visits have remained unchanged. In comparison to young adults, expanding insurance coverage to adolescents improved use of health care services and suggests a shift to non‐ED settings. Expanding insurance through the Affordable Care Act of 2010 will likely increase use of outpatient services, but may not decrease ED volumes.
A Re‐examination of Analyst Under‐reaction
Authors: Baik Bok , Lee Su Jeong
Published: October 2013

Prior studies suggest that analysts under‐react to past information (Klein, ; Abarbanell and Bernard, ; Easterwood and Nutt, ). We examine whether evidence interpreted as analyst under‐reaction to negative news can be attributed to analyst self‐selection. Analyst self‐selection arises when analysts' information production efforts are focused toward stocks that analysts expect to perform well. Using a large sample of firms for the period of 1983–2004, we find evidence suggesting that self‐selection is responsible, at least in part, for analyst under‐reaction to past negative information about the firm's performance.
Being in the users' shoes: Is there maybe another way?
Authors: Cowan John
Published: October 2013

This essay is in response to the paper “Being in the users' shoes: Anticipating experience while designing online courses” by Chrysi Rapanta and Lorenzo Cantoni (DOI: 10.1111/bjet.12102).
Outcomes of radical cystectomy with extended lymphadenectomy alone in patients with lymph node‐positive bladder cancer who are unfit for or who decline adjuvant chemotherapy
Authors: Zehnder Pascal , Studer Urs E. , Daneshmand Siamak , Birkhäuser Frédéric D. , Skinner Eila C. , Roth Beat , Miranda Gus , Burkhard Fiona C. , Cai Jie , Skinner Donald G. , Thalmann George N. , Gill Inderbir S.
Published: October 2013

Objective

To analyse the long‐term outcomes of patients with lymph node (LN)‐positive bladder cancer, who did not receive any adjuvant therapy after radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND).

Patients and Methods

We conducted a retrospective, combined cohort analysis based on two prospectively maintained cystectomy databases from the University of Southern California and the University of Bern.

Eligible patients underwent RC with ePLND for cN0M0 disease but were found to have LN‐positive disease.

No patient had neoadjuvant therapy, and all had negative surgical margins.

Kaplan–Meier plots were used to estimate recurrence‐free survival (RFS) and overall survival (OS). Subgroup comparisons were performed using log‐rank tests, and multivariable analysis was based on Cox proportional hazard models.

Results

Of 521 patients with LN‐positive disease, 251 (48%) never received adjuvant therapy.

Although the pathological stage distribution was similar, the 251 patients who did not receive adjuvant therapy were older and had both fewer total and positive LNs than those who underwent adjuvant therapy.

The median RFS for patients treated with RC alone was 1.6 years.

Recurrences mainly occurred <2 years after RC, resulting in 5‐ and 10‐year RFS rates of 32 and 26%, respectively.

Pathological T stage, the total number of LNs and the number of positive LNs detected were independent predictors of RFS and OS.

Conclusions

In this study, 25% of patients with documented LN metastases who did not receive adjuvant therapy were cured with RC and ePLND; however, a few relapses may occur later than 3 years.

Predictors of survival were pathological T stage, the number of total LNs and the number of positive LNs identified.
Donor pre‐treatment in clinical kidney transplantation: a critical appraisal
Authors: de Vries Dorottya K. , Wijermars Leonie G. M. , Reinders Marlies E. J. , Lindeman Jan H. N. , Schaapherder Alexander F. M.
Published: October 2013

Kidney transplantation represents one of the medical achievements of the 20th century. However, its continued success is limited by the increasing shortage of donor grafts. As a result, more kidney grafts from marginal donors are being considered for transplantation, with concomitantly more initial graft injury and limited organ and patient survival. This has led to an increased need for interventions aiming to optimize and preserve graft quality. Interventions within the donor may protect against ischemia/reperfusion injury, and therefore, donor pre‐treatment is a promising strategy to increase graft function and survival. During the last decade, diverse donor pre‐treatment interventions have been explored in animal studies. Moreover, the first human trials concerning donor pre‐treatment in kidney transplantation have provided encouraging results. Unfortunately, it remains difficult to determine how and where to intervene in the multifactorial and complex processes that affect the donor kidney. Moreover, ethical matters play a critical role in donor interventions, and pre‐treatment should principally not have any potentially unfavorable effects on other organs to be transplanted or on the living donor. This review provides an overview of promising therapeutical strategies for donor pre‐treatment in kidney transplantation and discusses the clinical trials that have been conducted thus far.
Stimulating ERK/PI3K/NFκB signaling pathways upon activation of mGluR2/3 restores OGD‐induced impairment in glutamate clearance in astrocytes
Authors: Lin Chia‐Ho , You Jie‐Ru , Wei Kai‐Che , Gean Po‐Wu
Published: October 2013

We used the oxygen and glucose deprivation (OGD) method in cultured astrocytes as anin vitroischemic model. We investigated whether activation of group‐II metabotropic glutamate receptors (mGluR2/3) can reverseOGD‐induced impairment in astrocytic glutamate/aspartate transporter (GLAST) expression and elucidated the signaling pathways involving theGLASTexpression. Cultured astrocytes exposed toOGDfor 6 h resulted in significant reductions in theGLASTexpression and extracellular glutamate clearance. These reductions were effectively restored bymGluR2/3 activation withmGluR2/3 agonists, LY379268 orDCG‐IV, after the 6 hOGDinsult. ThesemGluR2/3‐mediated restorative effects were inhibited by selectivemGluR2/3 antagonists LY341459 orEGLU. ThemGluR2/3 activation also induced activations of signaling pathways including extracellular signal‐regulated kinase (ERK), phosphatidylinositol 3‐kinase (PI3K) and nuclear transcription factor‐κB (NFκB). These activations were prevented by blockingmGluR2/3 with LY341459, anmGluR2/3 antagonist. Furthermore, blockingERK, PI3K and NFκB signaling pathways with U0126, LY294002 and pyrrolidine dithiocarbamate, respectively, significantly inhibited themGluR2/3‐mediated restorative effects. These results suggest that application ofmGluR2/3 agonists afterOGDinsult can effectively reverse theOGD‐reduced expression ofGLASTproteins and restore clearance of extracellular glutamate by serially activating ERK/PI3K/NFκB signaling pathways in cultured astrocytes.
Does periosteal scraping of the third metacarpal bone reduce the incidence of ‘bucked shins’ in young Thoroughbred racehorses?
Authors: Plevin S. , McLellan J.
Published: October 2013

Reasons for performing study

The occurrence of bucked shins in young Thoroughbred racehorses in North America is high. Although an altered training regime has demonstrated a significant decrease in this condition, trainers can be opposed to altering something as fundamental as their training routine. Periosteal scraping of the third metacarpal bone (McIII) is a putative prophylactic technique used to prevent bucked shins; therefore, a study to investigate the validity of the procedure is warranted.

Objectives

To investigate whether prophylactic McIII scraping: 1) reduces the incidence of bucked shins in juvenile Thoroughbred horses at race speeds (breeze); and 2) allows increased cumulative breeze miles before the onset of disease.

Study design

Nonrandomised prospective clinical study.

Methods

One hundred and seventy yearling Thoroughbreds from one farm, under one trainer, were enrolled in this study over one training season; 85 horses were treated and 85 horses were control animals. Horses were observed for bucked shins over 5 cumulative breeze miles. The objectives were evaluated by comparing incidence rates and Kaplan‐Meier plots.

Results

The incidence rate for bucked shins was 0.059 cases per breezed mile in the treatment group, compared with 0.103 cases per breezed mile in the control group. Comparison of Kaplan‐Meier plots of breeze miles for the 2 groups demonstrated a significant difference between groups (P = 0.035). Horses that developed bucked shins following periosteal shin scraping breezed an average of 3.52 miles before the onset of disease, compared to 2.50 miles for horses not prophylactically treated (P = 0.005).

Conclusions

Periosteal McIII scraping reduced the incidence rate of bucked shins. The procedure allowed treated horses to breeze greater cumulative distances before an incident but failed to prevent the disease over the long term. Further investigation into this commonly used prophylactic technique is required.
Vitiligo and alopecia areata: apples and oranges?
Authors: Harris John E.
Published: October 2013

Vitiligo and alopecia areata are common autoimmune diseases of the skin. Vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body, while alopecia areata is characterized by patchy hair loss primarily on the scalp, but may also involve other areas as well. At first glance, the two diseases appear to be quite different, targeting different cell types and managed using different treatment approaches. However, the immune cell populations and cytokines that drive each disease are similar, they are closely associated within patients and their family members, and vitiligo and alopecia areata have common genetic risk factors, suggesting that they share a similar pathogenesis. Like apples and oranges, vitiligo and alopecia areata have some obvious differences, but similarities abound. Recognizing both similarities and differences will promote research into the pathogenesis of each disease, as well as the development of new treatments.
Size Effects in the Pricing of Corporate Bonds
Authors: Kadiyala Padma , Viswanath P.V.
Published: October 2013

Large orders for corporate bonds get preferential treatment unlike large orders for stocks on the NYSE. A structural explanation, namely, that the corporate bond market is dealer‐dominated, has been offered for the favorable pricing. In this paper, we offer an additional explanation, namely, that the improved pricing for large orders is due to the net impact such orders have on a market maker's costs. Using a data sample that is substantially free of timing mismatch, we support our assertion by sorting the sample into ‘brokered’ trades, which are trades where the dealer merely crosses buy and sell orders and ‘inventoried’ trades, where the dealer trades out of his inventory. We find that large orders raise information costs, but lower inventory costs for ‘inventoried’ trades. The net result is a smaller price advantage than received by large orders on ‘brokered’ trades which are not subject to these costs.
Screening colonoscopy in HIV‐infected patients: high rates of mucosal abnormalities in a German HIV‐infected cohort
Authors: Kasapovic A , Boesecke C , Schwarze‐Zander C , Anadol E , Vogel M , Hippe V , Schmitz V , Rockstroh JK , Wasmuth JC
Published: October 2013

Objectives

Because of the improved life expectancy provided by successful antiretroviral combination therapy, preventive health measures in HIV‐infected patients have assumed increasing importance. To date, no data exist on rates of mucosal abnormalities detected by screening colonoscopy in > 50‐year‐old HIV‐infected patients in Germany. The aim of this study was to obtain such data.

Methods

A screening colonoscopy was offered to 159 HIV‐infected patients (age > 50 years) who presented for HIV standard of care visits at the infectious diseases out‐patient clinic at the university hospital in Bonn over a 1‐year period from February 2010. Pearson's χ2 test, Fisher's exact test and the Mann−Whitney U‐test were used for statistical analysis.

Results

Fifty‐one patients (32.1%) had undergone a screening colonoscopy in the past 10 years, and 45 patients (28.3%) were eventually screened in the observation period. The median age of the 96 screened patients (86% male and 14% female) was 58 years [interquartile range (IQR) 54–64 years]. Overall, endoscopic abnormalities were found in 61% of patients. Histological examination showed tubular adenomas in 21.9% of patients, tubulovillous adenomas in 3.1% and serrated adenomas in 1%. Hyperplastic polyps were found in 15.6% of patients, a nonspecific colitis in 16.7% and diverticulosis in 12.5%. In four cases there was even an early‐stage carcinoma (two anal, one rectal and one colon cancer). In univariate analysis, no significant differences with regard to immune status, highly active antiretroviral therapy, family history, personal risk factors or comedication were found between patients with dysplastic and normal mucosas.

Conclusions

The high acceptance rate of screening colonoscopy and the in comparison with the HIV‐negative population comparably higher rate of abnormalities in this cohort of HIV‐infected patients justify enhanced implementation of screening colonoscopy in clinical practice.
Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine
Authors: Halama A. , Riesen N. , Möller G. , Hrabě de Angelis M. , Adamski J.
Published: October 2013

Background

Metabolomics is a versatile unbiased method to search for biomarkers of human disease. In particular, one approach in cancer therapy is to promote apoptosis in tumour cells; this could be improved with specific biomarkers of apoptosis for monitoring treatment. We recently observed specific metabolic patterns in apoptotic cell lines; however, in that study, apoptosis was only induced with one pro‐apoptotic agent, staurosporine.

Objective

The aim of this study was to find novel biomarkers of apoptosis by verifying our previous findings using two further pro‐apoptotic agents, 5‐fluorouracil and etoposide, that are commonly used in anticancer treatment.

Methods

Metabolic parameters were assessed in HepG2 and HEK293 cells using the newborn screening assay adapted for cell culture approaches, quantifying the levels of amino acids and acylcarnitines with mass spectrometry.

Results

We were able to identify apoptosis‐specific changes in the metabolite profile. Moreover, the amino acids alanine and glutamate were both significantly up‐regulated in apoptotic HepG2 and HEK293 cells irrespective of the apoptosis inducer.

Conclusion

Our observations clearly indicate the potential of metabolomics in detecting metabolic biomarkers applicable in theranostics and for monitoring drug efficacy.
Analysis of growth and stable isotopes in teeth of male Australian fur seals reveals interannual variability in prey resources
Authors: Knox Travis C. , Stuart‐Williams Hilary , Warneke Robert M. , Hoskins Andrew J. , Arnould John P. Y.
Published: October 2013

To detect and monitor long‐term ecosystem responses to environmental variability, managers must utilize reliable and quantitative techniques to predict future ecosystem responses. Canine teeth from 67 male Australian fur seals (aged 2–19 yr), collected at Seal Rocks, between 1967 and 1976, were measured for relative growth within the dentine growth layer groups (GLGs), as an index of body growth. Fluctuations in relative growth were apparent during 1956–1971, suggesting interannual variation in prey resources within Bass Strait. These were positively correlated with the Southern Oscillation Index and negatively with the Indian Ocean Subtropical Dipole, both on a 2 yr lag. The observed delay may reflect the time required for the nutrient cascade to filter through to the predominantly benthic prey of Australian fur seals. Stable isotope analysis (δ15N/δ13C) was also used to investigate whether fluctuations in growth were associated with differences in diet. Relative growth was found to be negatively correlated with δ15N, suggesting years of greater resource availability may be associated with individuals consuming proportionally more prey biomass of lower isotopic value. This study demonstrates that fluctuations in the dentine GLGs of male Australian fur seals are related to environmental parameters, suggesting variation in body growth is mediated by changes in prey resources.
Agrobacterium T‐DNA‐encoded protein Atu6002 interferes with the host auxin response
Authors: Lacroix Benoît , Gizatullina Diana I. , Babst Benjamin A. , Gifford Andrew N. , Citovsky Vitaly
Published: October 2013

Several genes in the Agrobacterium tumefaciens transferred (T)‐DNA encode proteins that are involved in developmental alterations, leading to the formation of tumours in infected plants. We investigated the role of the protein encoded by the Atu6002 gene, the function of which is completely unknown. Atu6002 expression occurs in Agrobacterium‐induced tumours, and is also activated on activation of plant cell division by growth hormones. Within the expressing plant cells, the Atu6002 protein is targeted to the plasma membrane. Interestingly, constitutive ectopic expression of Atu6002 in transgenic tobacco plants leads to a severe developmental phenotype characterized by stunted growth, shorter internodes, lanceolate leaves, increased branching and modified flower morphology. These Atu6002‐expressing plants also display impaired response to auxin. However, auxin cellular uptake and polar transport are not significantly inhibited in these plants, suggesting that Atu6002 interferes with auxin perception or signalling pathways.
‘The progress of thy glorious book’: material reading and the play of paratext in Coryats Crudities (1611)
Authors: Palmer Philip S.
Published: October 2013

Coryats Crudities (1611), a 939‐page narrative of its author's five‐month journey through Western Europe, is well known as a strange amalgam of euphuistic prose travel writing and a substantial body of ‘Panegyricke Verses’, comprising over eighty mock encomiastic poems written by the likes of Ben Jonson, John Donne, Inigo Jones, and Sir John Harington (among others). Described by Thomas Coryate as a prose and verse ‘miscellany’, the volume enables a variety of readerly strategies for interpreting its mixed‐mode form, employing printed marginalia in particular to lend its miscellaneity a playfully referential structure. Material evidence left by seventeenth‐century readers, moreover, reveals a complex and imitative paratextual dialogue between the printed marginalia and manuscript additions to the volume. My case study of the extensively annotated copy surviving as Pierpont Morgan Library W 02 B, owned by the poet and writing master John Davies of Hereford and at least three, perhaps four additional seventeenth‐century readers, not only recovers valuable early approaches to reading Coryats Crudities, but investigates how those readers responded to various textual stimuli in the volume – from the author's incessant measurements to the satirical mode of the mock panegyrists – to construct the Crudities as both innovative travel book and site of elaborate literary play.
Perceptions of Randomized Security Schedules
Authors: Scurich Nicholas , John Richard S.
Published: October 2013

Security of infrastructure is a major concern. Traditional security schedules are unable to provide omnipresent coverage; consequently, adversaries can exploit predictable vulnerabilities to their advantage. Randomized security schedules, which randomly deploy security measures, overcome these limitations, but public perceptions of such schedules have not been examined. In this experiment, participants were asked to make a choice between attending a venue that employed a traditional (i.e., search everyone) or a random (i.e., a probability of being searched) security schedule. The absolute probability of detecting contraband was manipulated (i.e., 1/10, 1/4, 1/2) but equivalent between the two schedule types. In general, participants were indifferent to either security schedule, regardless of the probability of detection. The randomized schedule was deemed more convenient, but the traditional schedule was considered fairer and safer. There were no differences between traditional and random schedule in terms of perceived effectiveness or deterrence. Policy implications for the implementation and utilization of randomized schedules are discussed.
Identification of KIR3DL1*0050103 by the sequence‐based techniques
Authors: Yindom L.‐M. , Wang L. , Dong T. , Rowland‐Jones S. L.
Published: October 2013

The new KIR3DL1*0050103 allele has a mutation at nucleotide position 6709 (C>T) in intron 5.
Characteristics of flattening filter free beams at low monitor unit settings
Authors: Akino Yuichi , Ota Seiichi , Inoue Shinichi , Mizuno Hirokazu , Sumida Iori , Yoshioka Yasuo , Isohashi Fumiaki , Ogawa Kazuhiko
Published: October 2013

Purpose:

Newer linear accelerators (linacs) have been equipped to deliver flattening filter free (FFF) beams. When FFF beams are used for step‐and‐shoot intensity‐modulated radiotherapy (IMRT), the stability of delivery of small numbers of monitor units (MU) is important. The authors developed automatic measurement techniques to evaluate the stability of the dose profile, dose linearity, and consistency. Here, the authors report the performance of the Artiste™ accelerator (Siemens, Erlangen, Germany) in delivering low‐MU FFF beams.

Methods:

A 6 MV flattened beam (6X) with 300 MU/min dose rate and FFF beams of 7 (7XU) and 11 MV (11XU), each with a 500 MU/min dose rate, were measured at 1, 2, 3, 5, 8, 10, and 20 MU settings. For the 2000 MU/min dose rate, the 7 (7XUH) and 11 MV (11XUH) beams were set at 10, 15, 20, 25, and 30 MU because of the limits of the minimum MU settings. Beams with 20 × 20 and 10 × 10 cm2 field sizes were alternately measured ten times in intensity modulated (IM) mode, with which Siemens linacs regulate beam delivery for step‐and‐shoot IMRT. The in‐ and crossplane beam profiles were measured using a Profiler™ Model 1170 (Sun Nuclear Corporation, Melbourne, FL) in multiframe mode. The frames of 20 × 20 cm2 beams were identified at the off‐axis profile. The 6X beam profile was normalized at the central axis. The 7 and 11 MV FFF beam profiles were rescaled to set the dose at the central axis at 145% and 170%, respectively. Point doses were also measured using a Farmer‐type ionization chamber and water‐equivalent solid phantom to evaluate the linearity and consistency of low‐MU beam delivery. The values displayed on the electrometer were recognized with a USB‐type camera and read with open‐source optical character recognition software.

Results:

The symmetry measurements of the 6X, 7XU, and 11XU beam profiles were better than 2% for beams ≥2 MU and improved with increasing MU. The variations in flatness of FFF beams ≥2 MU were ±5%. The standard deviation of the symmetry and flatness also decreased with increasing MU. The linearity of the 6X beam was ±1% and ±2% for the beams of ≥5 and ≥3 MU, respectively. The 7XU and 11XU beams of ≥2 MU showed linearity with ±2% except the 7XU beam of 8 MU (+2.9%). The profiles of the FFF beams with 2000 and 500 MU/min dose rate were similar.

Conclusions:

The characteristics of low‐MU beams delivered in IM mode were evaluated using an automatic measurement system developed in this study. The authors demonstrated that the profiles of FFF beams of the Artiste™ linac were highly stable, even at low MU. The linearity of dose output was also stable for beams ≥2 MU.
Too Fast to Die
Authors: Brzostek Joanna , Gascoigne Nicholas R. J.
Published: October 2013

Imaging of developing T cells in thymic slices reveals distinct characteristics associated with positive versus negative selection.
Sprouting Vessels with Nrf2
Authors: Berndt Jason D.
Published: October 2013

Nrf2 enhances neovascularization by suppressing Delta-Notch signaling.
Bacterial Détente?
Authors: Hurtley Stella M.
Published: October 2013

A general bacterial defense mechanism suppresses the movement of horizontally transferred DNA in bacterial populations.
Hyperamylasaemia: pathognomonic to pancreatitis?
Authors: Burden Sam , Poon Anna Sau Kuk , Masood Kausar , Didi Mohamed
Published: October 2013

An 82-year-old woman, presented with a history of vomiting, abdominal mass and a significantly raised amylase, but no clinical evidence of pancreatitis. Abdominal ultrasound and CT scans showed an ovarian tumour, and no evidence of pancreatitis—as is often associated with a raised amylase. The patient underwent bilateral ovariectomy and hysterectomy and made a good recovery.
MICROMAGNETISM INDUCED BY THE UNPAIRED ELECTRONS IN InSb SINGLE CRYSTAL
Authors: GE MIN , TAN SHUN , PI LI , ZHANG YUHENG
Published: October 2013

In this paper, our experimental results demonstrate that the micromagnetism of InSb is determined by J (where J = L+S) instead of S of unpaired electrons due to the strong spin–orbit coupling. The results of macromagnetism show that the magnetism is diamagnetic, which comes from the Lamor moment of localized electrons and Landau diamagnetic moment of conduction electrons. Below 160 K, ferromagnetic ordering of J, which is induced by the interaction between J, also promotes the appearance of metallic behavior which is different from the well-known band theory.
THE MAGNETOINDUCTIVE DIMER
Authors: MOLINA MARIO I.
Published: October 2013

In this paper, we examine a nonlinear magnetoinductive dimer and compute its linear and nonlinear symmetric, antisymmetric and asymmetric modes in closed-form, in the rotating-wave approximation. A linear stability analysis of these modes reveals that the asymmetric mode is always stable, for any allowed value of the coupling parameter and for both, hard and soft nonlinearity. An exact numerical computation of the dimer dynamics reveals a magnetic energy self-trapping whose threshold increases for increasing dimer coupling, decreases for increasing nonlinearity response and is robust against asymmetrical nonlinear responses and resonant frequencies mismatch.
SPECTRAL DENSITY SCALING OF FLUCTUATING INTERFACES
Authors: KIM HYUN-JOO , JUNG DOIL
Published: October 2013

In this paper, covariance matrices of heights measured relative to the average height of growing self-affine surfaces in the steady state are investigated in the framework of random matrix theory. We show that the spectral density of the covariance matrix scales as ρ(λ) ~ λ-ν deviating from the prediction of random matrix theory and has a scaling form, ρ(λ, L) = λ-ν f(λ/Lϕ) for the lateral system size L, where the scaling function f(x) approaches a constant for λ ≪ Lϕ and zero for Lϕ≪λ< λ max . The values of exponents obtained by numerical simulations are ν ≈ 1.70 and ϕ ≈ 1.51 for the Edward–Wilkinson class and ν ≈ 1.61 and ϕ ≈ 1.76 for the Kardar–Parisi–Zhang class, respectively. The distribution of the largest eigenvalues follows a scaling form as ρ(λ max , L) = 1/Lb f max ((λ max - La)/Lb), which is different from the Tracy–Widom distribution of random matrix theory while the exponents a and b are given by the same values for the two different classes.