bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Immunogenicity of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administered to Children 10 or 11 Years of Age
Authors: Marshall Gary S. , Pool Vitali , Greenberg David P. , Johnson David R. , Sheng Xiaohua , Decker Michael D.
Published: September 2014

Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.)
Multilocus Sequence Typing (MLST) and Whole-Genome MLST of Campylobacter jejuni Isolates from Human Infections in Three Districts during a Seasonal Peak in Finland
Authors: Kovanen Sara M. , Kivistö Rauni I. , Rossi Mirko , Schott Thomas , Kärkkäinen Ulla-Maija , Tuuminen Tamara , Uksila Jaakko , Rautelin Hilpi , Hänninen Marja-Liisa
Published: September 2014

A total of 95 human
Campylobacter jejuni
isolates acquired from domestic infections and collected from three districts in Finland during the seasonal peak (June to September) in 2012 were analyzed by PCR-based multilocus sequence typing (MLST) and by whole-genome sequencing (WGS). Four predominant sequence types (STs) were detected among the isolates: ST-45 (21%) and ST-230 (14%, ST-45 clonal complex [CC]), ST-267 (21%, ST-283 CC), and ST-677 (19%, ST-677 CC). In districts 1 and 3, most of the infections occurred from early July to the middle of August, with a peak at weeks 29 to 31, but in district 2, the infections were dispersed more evenly throughout 3 months (June to August). WGS data were used for further whole-genome MLST (wgMLST) analyses of the isolates representing the four common STs. Shared loci of the isolates within each ST were analyzed as distance matrices of allelic profiles by the neighbor-net algorithm. The highest allelic variations (>400 different alleles) were detected between different clusters of ST-45 isolates (1,121 shared loci), while ST-230 (1,264 shared loci), ST-677 (1,169 shared loci), and ST-267 isolates (1,217 shared loci) were less diverse with the clusters differing by <40 alleles. Closely related isolates showing no allelic variation (subclusters) were detected among all four major STs. In some cases, they originated from different districts, suggesting that isolates can be epidemiologically connected and may have the same infection source despite being originally identified as sporadic infections.
Yeast On-Target Lysis (YOTL), a Procedure for Making Auxiliary Mass Spectrum Data Sets for Clinical Routine Identification of Yeasts
Authors: Bernhard Mareike , Weig Michael , Zautner Andreas E. , Groß Uwe , Bader Oliver
Published: September 2014

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS)-based species identification has become a reliable and fast tool for use in clinical diagnostics, including in mycology. To identify yeasts in the MALDI Biotyper system, a multistep extraction protocol, which is also used to generate the reference spectra, is recommended. Sample preparation by on-target lysis (OTL) requires significantly less hands-on time and is therefore highly desirable, but it results in too-low MALDI Biotyper log score values to allow automated species identification. To overcome this problem, we developed a procedure for generating and validating an OTL spectrum data set for the most relevant and frequently occurring yeast species in clinical specimens. The performance was evaluated against a set of OTL spectra derived during clinical routine procedures and from a set of closely related yeasts. In the diagnostic setting, the OTL procedure significantly decreased the workload but allowed species identification with high specificity and sensitivity. False identifications were not observed. The use of in-house-generated OTL reference spectra can highly accelerate MALDI-TOF MS-based yeast species identification using the MALDI Biotyper.
Comparative Genome Analysis of Four Elephant Endotheliotropic Herpesviruses, EEHV3, EEHV4, EEHV5, and EEHV6, from Cases of Hemorrhagic Disease or Viremia
Authors: Zong Jian-Chao , Latimer Erin M. , Long Simon Y. , Richman Laura K. , Heaggans Sarah Y. , Hayward Gary S.
Published: September 2014

The genomes of three types of novel endotheliotropic herpesviruses (elephant endotheliotropic herpesvirus 1A [EEHV1A], EEHV1B, and EEHV2) associated with lethal hemorrhagic disease in Asian elephants have been previously well characterized and assigned to a new
Proboscivirus
genus. Here we have generated 112 kb of DNA sequence data from segments of four more types of EEHV by direct targeted PCR from blood samples or necropsy tissue samples from six viremic elephants. Comparative phylogenetic analysis of nearly 30 protein-encoding genes of EEHV5 and EEHV6 show that they diverge uniformly by nearly 20% from their closest relatives, EEHV2 and EEHV1A, respectively, and are likely to have similar overall gene content and genome organization. In contrast, seven EEHV3 and EEHV4 genes analyzed differ from those of all other EEHVs by 37% and have a G+C content of 63% compared to just 42% for the others. Three strains of EEHV5 analyzed clustered into two partially chimeric subgroups EEHV5A and EEHV5B that diverge by 19% within three small noncontiguous segments totaling 6.2 kb. We conclude that all six EEHV types should be designated as independent species within a proposed new fourth
Deltaherpesvirinae
subfamily of mammalian herpesviruses. These virus types likely initially diverged close to 100 million years ago when the ancestors of modern elephants split from all other placental mammals and then evolved into two major branches with high- or low-G+C content about 35 million years ago. Later additional branching events subsequently generated three paired sister taxon lineages of which EEHV1 plus EEHV6, EEHV5 plus EEHV2, and EEHV4 plus EEHV3 may represent Asian and African elephant versions, respectively.

IMPORTANCE
One of the factors threatening the long-term survival of endangered Asian elephants in both wild range countries and in captive breeding populations in zoos is a highly lethal hemorrhagic herpesvirus disease that has killed at least 70 young Asian elephants worldwide. The genomes of the first three types of EEHVs (or probosciviruses) identified have been partially characterized in the preceding accompanying paper (
L. K. Richman, J.-C. Zong, E. M. Latimer, J. Lock, R. C. Fleischer, S. Y. Heaggans, and G. S. Hayward
, J. Virol. 88:13523–13546, 2014,
http://dx.doi.org/10.1128/JVI.01673-14
). Here we have used PCR DNA sequence analysis from multiple segments of DNA amplified directly from blood or necropsy tissue samples of six more selected cases of hemorrhagic disease to partially characterize four other types of EEHVs from either Asian or African elephants. We propose that all six types and two chimeric subtypes of EEHV belong to multiple lineages of both AT-rich and GC-rich branches within a new subfamily to be named the
Deltaherpesvirinae
, which evolved separately from all other mammalian herpesviruses about100 million years ago.
Expanded Regulatory T Cells in Chronically Friend Retrovirus-Infected Mice Suppress Immunity to a Murine Cytomegalovirus Superinfection
Authors: Duppach Janine , Francois Sandra , Joedicke Jara J. , Dittmer Ulf , Kraft Anke R. M.
Published: September 2014

It is still unclear whether expanded and activated regulatory T cells (Tregs) in chronic viral infections can influence primary immune responses against superinfections with unrelated viruses. Expanded Tregs found in the spleens of chronically Friend virus (FV)-infected mice decreased murine cytomegalovirus (mCMV)-specific CD8
+
T cell responses during acute mCMV superinfection. This suppression of mCMV-specific T cell immunity was found only in organs with FV-induced Treg expansion. Surprisingly, acute mCMV infection itself did not expand or activate Tregs.
Structural Plasticity of the Coiled-Coil Domain of Rotavirus NSP4
Authors: Sastri Narayan P. , Viskovska Maria , Hyser Joseph M. , Tanner Mark R. , Horton Lori B. , Sankaran Banumathi , Prasad B. V. Venkataram , Estes Mary K.
Published: September 2014

Rotavirus (RV) nonstructural protein 4 (NSP4) is a virulence factor that disrupts cellular Ca
2+
homeostasis and plays multiple roles regulating RV replication and the pathophysiology of RV-induced diarrhea. Although its native oligomeric state is unclear, crystallographic studies of the coiled-coil domain (CCD) of NSP4 from two different strains suggest that it functions as a tetramer or a pentamer. While the CCD of simian strain SA11 NSP4 forms a tetramer that binds Ca
2+
at its core, the CCD of human strain ST3 forms a pentamer lacking the bound Ca
2+
despite the residues (E120 and Q123) that coordinate Ca
2+
binding being conserved. In these previous studies, while the tetramer crystallized at neutral pH, the pentamer crystallized at low pH, suggesting that preference for a particular oligomeric state is pH dependent and that pH could influence Ca
2+
binding. Here, we sought to examine if the CCD of NSP4 from a single RV strain can exist in two oligomeric states regulated by Ca
2+
or pH. Biochemical, biophysical, and crystallographic studies show that while the CCD of SA11 NSP4 exhibits high-affinity binding to Ca
2+
at neutral pH and forms a tetramer, it does not bind Ca
2+
at low pH and forms a pentamer, and the transition from tetramer to pentamer is reversible with pH. Mutational analysis shows that Ca
2+
binding is necessary for the tetramer formation, as an E120A mutant forms a pentamer. We propose that the structural plasticity of NSP4 regulated by pH and Ca
2+
may form a basis for its pleiotropic functions during RV replication.

IMPORTANCE
The nonstructural protein NSP4 of rotavirus is a multifunctional protein that plays an important role in virus replication, morphogenesis, and pathogenesis. Previous crystallography studies of the coiled-coil domain (CCD) of NSP4 from two different rotavirus strains showed two distinct oligomeric states, a Ca
2+
-bound tetrameric state and a Ca
2+
-free pentameric state. Whether NSP4 CCD from the same strain can exist in different oligomeric states and what factors might regulate its oligomeric preferences are not known. This study used a combination of biochemical, biophysical, and crystallography techniques and found that the NSP4 CCD can undergo a reversible transition from a Ca
2+
-bound tetramer to a Ca
2+
-free pentamer in response to changes in pH. From these studies, we hypothesize that this remarkable structural adaptability of the CCD forms a basis for the pleiotropic functional properties of NSP4.
Internal jugular vein thrombosis complicating disseminated tuberculosis in a 2-year-old child
Authors: Das Sarthak , Srinivasaraghavan Rangan , Krishnamurthy Sriram , Mahadevan Subramanian
Published: September 2014

Internal jugular vein (IJV) thrombosis is a serious and potentially life-threatening occurrence in children, and is usually associated with malignancies, prolonged central venous catheterisation or deep seated head and neck infections or trauma. It has not been described in association with tuberculosis in children. The authors describe a 2-year-old child who presented with IJV thrombosis in association with clinical signs and symptoms of disseminated tuberculosis. There was complete resolution of symptoms after starting antitubercular drugs and warfarin. The authors emphasise that an active search for tuberculosis should be made routinely in patients with IJV thrombosis with an underlying mediastinal mass and/or generalised lymphadenopathy.
The INCENTIVE protocol: an evaluation of the organisation and delivery of NHS dental healthcare to patients—innovation in thecommissioning of primary dental care service delivery and organisation in the UK
Authors: Pavitt Sue H , Baxter Paul D , Brunton Paul A , Douglas Gail , Edlin Richard , Gibson Barry J , Godson Jenny , Hall Melanie , Porritt Jenny , Robinson Peter G , Vinall Karen , Hulme Claire
Published: September 2014

Introduction

In England, in 2006, new dental contracts devolved commissioning of dental services locally to Primary Care Trusts to meet the needs of their local population. The new national General Dental Services contracts (nGDS) were based on payment for Units of Dental Activity (UDAs) awarded in three treatment bands based on complexity of care. Recently, contract currency in UK dentistry is evolving from UDAs based on volume and case complexity towards ‘blended contracts’ that include incentives linked with key performance indicators such as quality and improved health outcome. Overall, evidence of the effectiveness of incentive-driven contracting of health providers is still emerging. The INCENTIVE Study aims to evaluate a blended contract model (incentive-driven) compared to traditional nGDS contracts on dental service delivery in practices in West Yorkshire, England.

Methods and analysis

The INCENTIVE model uses a mixed methods approach to comprehensively evaluate a new incentive-driven model of NHS dental service delivery. The study includes 6 dental surgeries located across three newly commissioned dental practices (blended contract) and three existing traditional practices (nGDS contracts). The newly commissioned practices have been matched to traditional practices by deprivation index, age profile, ethnicity, size of practice and taking on new patients. The study consists of three interlinked work packages: a qualitative study to explore stakeholder perspectives of the new service delivery model; an effectiveness study to assess the INCENTIVE model in reducing the risk of and amount of dental disease and enhance oral health-related quality of life in patients; and an economic study to assess cost-effectiveness of the INCENTIVE model in relation to clinical status and oral health-related quality of life.

Ethics and dissemination

The study has been approved by NRES Committee London, Bromley. The results of this study will be disseminated at national and international conferences and in international journals.
A cross-sectional study on informed choice in the mammography screening programme in Germany (InEMa): a study protocol
Authors: Berens Eva-Maria , Reder Maren , Kolip Petra , Spallek Jacob
Published: September 2014

Introduction

Breast cancer is the most prevalent cancer among women. In Germany, women are invited to a population-based mammography screening programme for the first time at the age of 50. Since it is still discussed whether the benefits of mammography screening outweigh its harms, the concept of informed choice has gained importance. The objective of this cross-sectional study is to assess the proportion of informed choices in the mammography screening programme. A special focus is on the examination of the impact of Turkish migration background and educational level on informed choices.

Methods and analysis

The proportion of informed choices is evaluated in a cross-sectional study with 3-month follow-up for behavioural implementation of the screening intention. A randomly selected sample of 17 000 women aged 50 years living in Westphalia-Lippe, a region in the Federal State of North-Rhine Westphalia, is invited to participate in this study. To reach adequate numbers of Turkish women, all possibly Turkish women in the sample are identified through a name algorithm and contacted. The sample is drawn from women registered in the study area for which the registration offices consented to supply data for the study (88% of all towns/cities in the study region). Women identified through the Turkish name algorithm received all materials in German and Turkish. The primary outcome is informed choice. Data are collected on informed choice components (knowledge, attitude, decision/implementation) as well as on its possible determinants (eg, health behaviour, perceived behavioural control, subjective norms, invitation status, migration background and other demographic variables). Data are collected before the screening appointment and at 3 months follow-up.

Ethics and dissemination

The study was approved by the ethical committee of the Medical Faculty of Muenster University. Results will be published in a relevant scientific journal and communicated to respondents and relevant institutions.
A session of resistance exercise increases vasodilation in intermittent claudication patients
Authors: Lima Aluísio , Ritti-Dias Raphael , Forjaz Cláudia L.M. , Correia Marilia , Miranda Alessandra , Brasileiro-Santos Maria , Santos Amilton , Sobral Filho Dario , Silva Alexandre
Published: September 2014

No study has shown the effects of acute resistance exercise on vasodilatory capacity of patients with peripheral artery disease. The aim of this study was to analyse the effects of a single session of resistance exercise on blood flow, reactive hyperemia, plasma nitrite, and plasma malondialdehyde in patients with peripheral artery disease. Fourteen peripheral artery disease patients underwent, in a random order, 2 experimental sessions: control (rest for 30 min) and resistance exercise (8 exercises, 2 sets of 10 repetitions at an intensity of 5–7 in the OMNI Resistance Exercise Scale). Blood flow, reactive hyperemia, plasma nitrite, and malondialdehyde were measured before and 40 min after the interventions in both sessions. Data were compared between sessions by analysis of covariance, using pre-intervention values as covariates. The increases in blood flow, reactive hyperemia, and log plasma nitrite were greater (p ≤ 0.05) after resistance exercise than the control session (3.2 ± 0.1 vs. 2.7 ± 0.1 mL·100 mL−1tissue·min−1, 8.0 ± 0.1 vs. 5.7 ± 0.1 AU, and 1.36 ± 0.01 vs. 1.26 ± 0.01 μmol∙L−1, respectively). On the other hand, malondialdehyde was similar between sessions (p > 0.05). In peripheral arterial disease patients, a single session of resistance exercise increases blood flow and reactive hyperemia, which seems to be mediated, in part, by increases in nitric oxide release.
Riboflavin-shuttled extracellular electron transfer from Enterococcus faecalis to electrodes in microbial fuel cells
Authors: Zhang Enren , Cai Yamin , Luo Yue , Piao Zhe
Published: September 2014

Great attention has been focused on Gram-negative bacteria in the application of microbial fuel cells. In this study, the Gram-positive bacterium Enterococcus faecalis was employed in microbial fuel cells. Bacterial biofilms formed by E. faecalis ZER6 were investigated with respect to electricity production through the riboflavin-shuttled extracellular electron transfer. Trace riboflavin was shown to be essential for transferring electrons derived from the oxidation of glucose outside the peptidoglycan layer in the cell wall of E. faecalis biofilms formed on the surface of electrodes, in the absence of other potential electron mediators (e.g., yeast extract).
Enhancing Corporate Governance in High-Growth Entrepreneurial Firms
Authors: Ahn Mark J.
Published: September 2014

This study explores how new ventures access advice to achieve high growth and sustainable performance. A relational model of three important themes — compliance (regulatory and legal governance), contacts (networks of suppliers, customers, investors), and content (strategic insights) — emerged as critical to any sustainable high-growth effort. Our findings suggest that advisory boards and boards of directors have a significant role in managing and creating value for emerging high-growth firms due to inherently high failure rates, technological complexity, and market risk — all of which requires access to external resources.
Adhesion-Mediated Signalling in Cancer: Recent Advances and Mathematical Modelling
Authors: Crociani Olivia , Becchetti Andrea , Fanelli Duccio , Arcangeli Annarosa
Published: September 2014

Cancer can be viewed as a "tissue", where neoplastic cells are immersed into a peculiar microenvironment (the "tumor microenvironment", TME) which modulates tumor cell behaviour during multistep tumorigenesis. Based on this concept, antineoplastic therapy should be tuned to target not only tumor cells but also the cellular constituents of the TME. Such necessity is well exemplified by considering tumor angiogenesis, a major aspect of cancer biology.

Ion channels and transporters are increasingly recognized as relevant players in the tumor cell-TME cross-talk. For example, during tumor neo-angiogenesis, soluble factors as well as fixed components of the extracellular matrix (ECM) and membrane proteins determine signal exchange between the TME and the implicated cell types. The signalling network is coordinated by functional "hubs", which may be constituted by integrin receptors associated with other proteins to form macromolecular signalling platforms at the adhesive sites. These complexes often include ion channels.

The K+channels encoded by the human ether-à-go-go related gene (Kv11.1, or hERG1) are frequently overexpressed in human cancers and regulate intracellular signalling by physically associating with integrin subunits and growth factor/chemokine receptors. In colorectal cancer (CRC) we recently identified a novel signalling pathway centered on hERG1 channels and integrins. This pathway involves the p53 protein, which is encoded by a tumor suppressor gene often mutated in human cancers. p53 controls angiogenesis, through a mechanism regulated by hERG1 K+channels. The central role played by hERG1 in CRC angiogenesis suggests that targeting hERG1 may be an effective therapeutic option in patients with advanced CRC.

To better understand the above process, it is necessary to study the interlaced dynamics of the key microscopic actors by using dedicated mathematical models. We here review a simple model, of reductionist inspiration, that explores the intimate connections between apoptosis and hypoxia, passing through angiogenesis. We show that a dynamical switch takes place between the normoxia and cellular death conditions. When oxygen lacks, cells can cross the transition line and so gain their way towards the normoxia regime, by implementing point mutations that affect the p53 production and activation rate, with the involvement of K+ion homeostasis, in agreement with the experimental observations.
Adversary degree associated reconstruction number of graphs
Authors: Monikandan S. , Sundar Raj S.
Published: September 2014

A vertex-deleted subgraph of a graph G is called a card of G. A card of G with which the degree of the deleted vertex is also given is called a degree associated card or dacard of G. The adversary degree associated reconstruction number of a graph G, adrn (G), is the minimum number k such that every collection of k dacards of G uniquely determines G. We prove that adrn (G) = 1 + min {t+1, m-t} or 1 + min {t, m - t + 2} for a graph G obtained by subdividing t edges of K1, m. We also prove that if G is a nonempty disconnected graph whose components are cycles or complete graphs, then adrn (G) is 3 or 4, while, if G is a double star whose central vertices have degrees m + 1 and n + 1(m > n ≥ 2), then adrn (G) can be as large as n + 3.
Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation
Authors: Münzer Patrick , Schmid Evi , Walker Britta , Fotinos Anna , Chatterjee Madhumita , Rath Dominik , Vogel Sebastian , Hoffmann Sascha M. , Metzger Katja , Seizer Peter , Geisler Tobias , Gawaz Meinrad , Borst Oliver , Lang Florian
Published: September 2014

Sphingosine 1-phosphate (S1P) is a powerful regulator of platelet formation. Enzymes generating S1P include sphingosine kinase 1. The present study thus explored the role of sphingosine kinase 1 in platelet formation and function. Activation-dependent platelet integrin αIIbβ3 activation and secretion of platelets lacking functional sphingosine kinase 1 ( sphk1 −/−) and of wild-type platelets ( sphk1 +/+) were determined utilizing flow cytometry and chronolume luciferin assay. Cytosolic Ca2+ activity ([Ca2+]i) and aggregation were measured using fura-2 fluorescence and aggregometry, respectively. In vitro platelet adhesion and thrombus formation were evaluated using a flow chamber with shear rates of 1,700 s−1. Activation-dependent increase of [Ca2+]i, degranulation (release of alpha and dense granules), integrin αIIbβ3 activation, and aggregation were all significantly increased in sphk1 −/− platelets compared with sphk1 +/+ platelets. Moreover, while platelet adhesion and thrombus formation under arterial shear rates were significantly augmented in Sphk1-deficient platelets, bleeding time and blood count were unaffected in sphk1 −/− mice. In conclusion, sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation.
Therapeutic potential of intermittent hypoxia: a matter of dose
Authors: Navarrete-Opazo Angela , Mitchell Gordon S.
Published: September 2014

Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigation, including potentially the severity of hypoxia within episodes, the duration of hypoxic episodes, the number of hypoxic episodes per day, the pattern of presentation across time (e.g., within vs. consecutive vs. alternating days), and the cumulative time of exposure. Not surprisingly, severe/chronic IH protocols tend to be pathogenic, whereas any beneficial effects are more likely to arise from modest/acute IH exposures. Features of the IH protocol most highly associated with beneficial vs. pathogenic outcomes include the level of hypoxemia within episodes and the number of episodes per day. Modest hypoxia (9–16% inspired O2) and low cycle numbers (3–15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2–8% inspired O2) and more episodes per day (48–2,400 episodes/day) elicit progressively greater pathology. Accumulating evidence suggests that “low dose” IH (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders.
Auditory evoked fields measured noninvasively with small-animal MEG reveal rapid repetition suppression in the guinea pig
Authors: Christianson G. Björn , Chait Maria , de Cheveigné Alain , Linden Jennifer F.
Published: September 2014

In animal models, single-neuron response properties such as stimulus-specific adaptation have been described as possible precursors to mismatch negativity, a human brain response to stimulus change. In the present study, we attempted to bridge the gap between human and animal studies by characterising responses to changes in the frequency of repeated tone series in the anesthetised guinea pig using small-animal magnetoencephalography (MEG). We showed that 1) auditory evoked fields (AEFs) qualitatively similar to those observed in human MEG studies can be detected noninvasively in rodents using small-animal MEG; 2) guinea pig AEF amplitudes reduce rapidly with tone repetition, and this AEF reduction is largely complete by the second tone in a repeated series; and 3) differences between responses to the first (deviant) and later (standard) tones after a frequency transition resemble those previously observed in awake humans using a similar stimulus paradigm.
Dietary Conjugated Linoleic Acid Supplementation Leads to Downregulation of PPAR Transcription in Broiler Chickens and Reduction of Adipocyte Cellularity
Authors: Ramiah Suriya Kumari , Meng Goh Yong , Sheau Wei Tan , Swee Keong Yeap , Ebrahimi Mahdi
Published: September 2014

Conjugated linoleic acids (CLA) act as an important ligand for nuclear receptors in adipogenesis and fat deposition in mammals and avian species. This study aimed to determine whether similar effects are plausible on avian abdominal fat adipocyte size, as well as abdominal adipogenic transcriptional level. CLA was supplemented at different levels, namely, (i) basal diet without CLA (5% palm oil) (CON), (ii) basal diet with 2.5% CLA and 2.5% palm oil (LCLA), and (iii) basal diet with 5% CLA (HCLA).The content ofcis-9,trans-11 CLA was between 1.69- and 2.3-fold greater (P<0.05) than that oftrans-10,cis-12 CLA in the abdominal fat of the LCLA and HCLA group. The adipogenic capacity of the abdominal fat depot in LCLA and HCLA fed chicken is associated with a decreased proportion of adipose cells and monounsaturated fatty acids (MUFA). The transcriptional level of adipocyte protein (aP2) and peroxisome proliferator-activated receptor gamma (PPARγ) was downregulated by 1.08- to 2.5-fold in CLA supplemented diets, respectively. It was speculated that feeding CLA to broiler chickens reduced adipocyte size and downregulated PPARγand aP2 that control adipocyte cellularity. Elevation of CLA isomers into their adipose tissue provides a potential CLA-rich source for human consumption.
Modular Leech Trees of Order at Most 8
Authors: Leach David
Published: September 2014

In 1975, John Leech asked when can the edges of a tree on n vertices be labeled with positive integers such that the sums along the paths are exactly the integers 1, 2, …, n2. He found five such trees, and no additional trees have been discovered since. In 2011 Leach and Walsh introduced the idea of labeling trees with elements of the group Zk where k=n2+1 and examined the cases for n≤6. In this paper we show that no modular Leech trees of order 7 exist, and we find all modular Leech trees of order 8.
Reconstruction of Dielectric Constants of Core and Cladding of Optical Fibers Using Propagation Constants Measurements
Authors: Karchevskii E. M. , Spiridonov A. O. , Repina A. I. , Beilina L.
Published: September 2014

We present new numerical methods for the solution of inverse spectral problem to determine the dielectric constants of core and cladding in optical fibers. These methods use measurements of propagation constants. Our algorithms are based on approximate solution of a nonlinear nonselfadjoint eigenvalue problem for a system of weakly singular integral equations. We study three inverse problems and prove that they are well posed. Our numerical results indicate good accuracy of new algorithms.
Counting Irreducible Polynomials of Degree r over Fqn and Generating Goppa Codes Using the Lattice of Subfields of Fqnr
Authors: Magamba Kondwani , Ryan John A.
Published: September 2014

The problem of finding the number of irreducible monic polynomials of degree r over Fqn is considered in this paper. By considering the fact that an irreducible polynomial of degree r over Fqn has a root in a subfield Fqs of Fqnr if and only if (nr/s,r)=1, we show that Gauss’s formula for the number of monic irreducible polynomials can be derived by merely considering the lattice of subfields of Fqnr . We also use the lattice of subfields of Fqnr to determine if it is possible to generate a Goppa code using an element lying in a proper subfield of Fqnr.
Parameter Estimation of Turbo Code Encoder
Authors: Teimouri Mehdi , Hedayat Ahmadreza
Published: September 2014

The problem of reconstruction of a channel code consists of finding out its design parameters solely based on its output. This paper investigates the problem of reconstruction of parallel turbo codes. Reconstruction of a turbo code has been addressed in the literature assuming that some of the parameters of the turbo encoder, such as the number of input and output bits of the constituent encoders and puncturing pattern, are known. However in practical noncooperative situations, these parameters are unknown and should be estimated before applying reconstruction process. Considering such practical situations, this paper proposes a novel method to estimate the above-mentioned code parameters. The proposed algorithm increases the efficiency of the reconstruction process significantly by judiciously reducing the size of search space based on an analysis of the observed channel code output. Moreover, simulation results show that the proposed algorithm is highly robust against channel errors when it is fed with noisy observations.
HER2-Positive Metaplastic Spindle Cell Carcinoma Associated with Synchronous Bilateral Apocrine Carcinoma of the Breast
Authors: Kito Katsumi , Maeda Toshiharu , Ninomiya Keiko , Sugita Atsuro , Sagawa Teiri , Matsuoka Kinya , Kinoshita Kousei , Hyodo Naoki , Morita Nagisa , Furuya Keizo
Published: September 2014

Apocrine carcinoma, which is strictly defined as over 90% of tumor cells showing apocrine differentiation, is a rare variant of breast cancer. Here we report an uncommon case in which apocrine carcinomas developed concurrently in both breasts; in addition, a sarcomatoid spindle cell lesion was coincident in the right breast. Both apocrine carcinomas were immunohistochemically negative for estrogen receptor (ER) and progesterone receptor (PgR), but diffusely positive for androgen receptor (AR), GCDFP-15, and HER2. The presence of intraductal components in bilateral carcinomas and the absence of lymph node metastasis suggested that they were more likely to be individual primary lesions rather than metastatic disease. The spindle cell lesion showed a relatively well-circumscribed nodule contiguous with the apocrine carcinoma. HER2 oncoprotein overexpression was observed not only in the apocrine carcinoma, but also in the spindle cell lesion. Since the spindle cell component was intimately admixed with apocrine carcinoma and had focal cytokeratin expression, we diagnosed it as metaplastic spindle cell carcinoma, which was originated from the apocrine carcinoma. To our knowledge, this is the first case report of a patient with synchronous bilateral apocrine carcinomas coinciding with metaplastic carcinoma.
Obstetric Scar Endometriosis: Retrospective Study on 19 Cases and Review of the Literature
Authors: Kaplanoglu Mustafa , Kaplanoğlu Dilek Kaya , Dincer Ata Ceren , Buyukkurt Selim
Published: September 2014

Endometriosis is defined as the presence of functioning endometrial tissue outside the uterine cavity. This disease is one of the most common gynecologic disorders in reproductive age women. It generally occurs in pelvic cavity. But extrapelvic location has been defined (such as extremities, central nervous system, lungs, pleurae, liver, umbilicus, pericardium, urinary tract, intestines, and surgical scar tissue). Scar endometriosis is a rare disease and defined as presence of endometriotic lesions on the abdominal (such as cesarean section and hysterectomy) or vaginal (episiotomy) excision line. It is difficult to diagnose due to the extreme variability in presentation. The symptoms are nonspecific, typically involving pain, swelling at the incision site at the time of menstruation. Excision and histopathologic examination are necessary for diagnosis. We present a case series of obstetric scar endometriosis and review of the literature.
Breakfast Time Blackouts
Authors: Barritt Andrew W. , MacDonald Bridget K.
Published: September 2014

We present the case of a 16-year-old girl who suffered from repeated episodes of collapse and loss of consciousness which could be provoked by undertaking a stretching manoeuvre comprising a combined breath hold and neck torsion. A review of the literature is provided on other cases of so-called “stretch syncope” which appears to be a rare form of reflex syncope affecting patients in adolescence.
Effect of Physician Gender on Demand for Pap Tests
Authors: Lin Tsui-Fang , Chen Jennjou
Published: September 2014

People’s demand for preventive medical care is one type of investment in health. The aim of this paper is to examine women’s demand for secondary prevention in Taiwan, focusing on the role a physician’s gender plays in women’s inclination to undergo Pap tests. Our estimation results show that regional ratio of female doctors has a positive and significant effect on utilization of Pap tests for the full sample and for women aged below 30. In addition, doctor’s gender matters only in utilization of Pap tests not in other types of preventive healthcare services in Taiwan. We suggest that the government may consider liberalizing medical laws to make it legal for trained female nurses or nurse practitioners to perform Pap tests in order to encourage the utilization of Pap tests, especially in rural and mountain areas. The government may also consider subsidizing the use of cervical cancer vaccines to help females prevent cervical cancer.
An Unusual Cause of Cardiac Tamponade during Cardiac Catheterization Study
Authors: Das Deepanwita , Datta Monalisa , Dey Somnath , Parida Jyotiranjan , Kumar Rupesh , Pande Arindam
Published: September 2014

Introduction.Catheter-based diagnostic and therapeutic procedures are rapidly advancing. However, catheter related complications sometimes become life threatening. Cardiac tamponade is a rare but serious complication of this procedure. We have summarized one cardiac tamponade pejoration due to secondary coronary vessels laceration by the implanted pericardial drainage.Case report. A 4-year-old baby having Tetralogy of Fallot was posted for diagnostic catheterization study. Patient was induced with sevoflurane and spontaneous respiration was maintained. After catheter insertion to RV, dye was injected through the catheter which rapidly spread into the pericardial cavity indicating right ventricle perforation. Immediately, blood was aspirated under transthoracic echocardiographic guidance and hemodynamics started improving. For the provision of quick access to aspirate further collection, an intrapericardial sheath was inserted after multiple attempts. Patient’s condition started deteriorating again. TTE revealed again some collection and it was increasing gradually. On exploration, it was found that there was continuous bleeding from a lacerated epicardial vessel which contributed to the pericardial collection leading to further tamponade effect. This second iatrogenic injury complicated the management of the first iatrogenic cardiac perforation and, thereby, created a life-threatening situation which needed immediate surgical exploration.Discussion. Usual cause of tamponade after right ventricular perforation is bleeding from the RV, but in our case the second tamponade was not due to bleeding from the RV, but was rather from new laceration injury of epicardial vessels which was remained undiagnosed till exploration.
The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases
Authors: Ferreira Caroline Marcantonio , Vieira Angélica Thomaz , Vinolo Marco Aurelio Ramirez , Oliveira Fernando A. , Curi Rui , Martins Flaviano dos Santos
Published: September 2014

The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.
The Registration of the Mid-Paleocene Biotic Event (MPBE) in Tunisia
Authors: Karoui-Yaakoub Narjess , Mtimet Moncef Saïd , Negra Mohamed Hédi , Grira Chaima , Gusemi Wafa
Published: September 2014

In Tunisia, the Paleocene biomarkers are identified within the El Haria Formation shales. The Selandian is absent in most of the Paleocene outcrops and the Thanetian is unconformable to different stages of the Cretaceous. In the middle of Selandian, with the beginning of the Globanomalina pseudomenardii (P4) zone, we note that the assemblage of planktonic foraminifera becomes very poorly preserved and much less abundant than at the base. It is represented by rare species and there has been a start of the microfauna dissolution tests and an enrichment in iron oxides, silica, and gypsum crystals. The dissolution process is increasing more and more and a drop in the content of carbonates is clearly recorded at the top of Selandian. However, we note that some small benthic foraminifera belonging to the genera Lenticulina and Anomalina escape the dissolution and very few planktonic foraminifera belonging to the genera Subbotina are preserved. This dramatic and abnormal dissolution extends over a considerable thickness. These features could be an expression of the mid-Paleocene biotic event (MPBE), registered for the first time in Tunisia. This intense dissolution is caused probably by the change in the solubility of carbonates, which may be related to the changes in the deep-water circulation or to the change in the productivity of the surface waters.
Raising the Bar for Antineoplastic Agents: How to Choose Threshold Values for Superiority Trials in Advanced Solid Tumors
Authors: Sobrero Alberto F. , Pastorino Alessandro , Sargent Daniel J. , Bruzzi Paolo
Published: September 2014

Purpose: To establish the concept of minimum clinically meaningful outcome (mCMO) of treatment in advanced solid tumors, to establish its threshold and evaluate how many superiority trials of new antineoplastic agents pass this threshold.

Experimental Design: We chose overall survival as the primary indicator of patient benefit. Four conceptually different types of treatment effect can be identified in OS curves: HR, gains in median OS, proportional, and absolute increases at long-term OS. We postulated threshold levels for these four parameters defining the mCMO and set the bar at three different levels of required benefit: high, medium, and low. The postulated values were then studied by comparing our thresholds with the actual results of the pivotal superiority phase III trials on new drugs reporting on mature OS data.

Results: Forty-three trials on 35,419 patients in 12 cancer types on 23 novel agents met these criteria. Only two trials reached the postulated “high” thresholds for HR and median OS. The number of “positive trials” increased to eight and 15 when the bar was lowered to the “medium” and “low” levels, respectively. The same analysis was done for proportional and absolute increases in long-term OS. No trial satisfied the criteria for long-term benefit, whereas only two and nine trials satisfied both parameters for the “medium and low” required benefit levels, respectively.

Conclusions: All four OS-related parameters contribute to define the mCMO. If the bar for the mCMO is raised too much, positive trials are exceptional. Clin Cancer Res; 21(5); 1036–43. ©2014 AACR.

See related commentary by Schilsky, p. 947
Bile Acids Regulate Nuclear Receptor (Nur77) Expression and Intracellular Location to Control Proliferation and Apoptosis
Authors: Hu Ying , Chau Thinh , Liu Hui-Xin , Liao Degui , Keane Ryan , Nie Yuqiang , Yang Hui , Wan Yu-Jui Yvonne
Published: September 2014

Bile acids (BA) are endogenous agents capable of causing cancer throughout the gastrointestinal (GI) tract. To uncover the mechanism by which BAs exert carcinogenic effects, both human liver and colon cancer cells as well as mouse primary hepatocytes were treated with BAs and assayed for viability, genotoxic stress, and transcriptional response. BAs induced both Nur77 (NR4A1) and proinflammatory gene expression. The intracellular location of BA-induced Nur77 was time dependent; short-term (1–3 hours) exposure induced nuclear Nur77, whereas longer (1–2 days) exposure also increased cytosolic Nur77 expression and apoptosis. Inhibiting Nur77 nuclear export with leptomycin B decreased lithocholic acid (LCA)-induced apoptosis. Extended (7 days) treatment with BA generated resistance to BA with increased nuclear Nur77, viability, and mobility. While, knockdown of Nur77 in BA-resistant cells increased cellular susceptibility to LCA-induced apoptosis. Moreover, in vivo mouse xenograft experiments demonstrated that BA-resistant cells form larger tumors with elevated Nur77 expression compared with parental controls. DNA-binding and gene expression assays identified multiple survival genes (CDK4, CCND2, MAP4K5, STAT5A, and RBBP8) and a proapoptosis gene (BID) as Nur77 targets. Consistently, BA-induced upregulation of the aforementioned genes was abrogated by a lack of Nur77. Importantly, Nur77 was overexpressed in high percentage of human colon and liver cancer specimens, and the intracellular location of Nur77 correlated with elevated serum total BA levels in patients with colon cancer. These data show for the first time that BAs via Nur77 have a dual role in modulating cell survival and death.

Implications: These findings establish a direct link between Nur77 and the carcinogenic effect of BAs. Mol Cancer Res; 13(2); 281–92. ©2014 AACR.