bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B in pregnancy
Authors: Dyson Jessica Katharine , Waller Julia , Turley Andrena , Michael Enid , Moses Samuel , Valappil Manoj , Hudson Mark , Bassendine Margaret , McPherson Stuart
Published: October 2013

Objective

Vertical transmission of the hepatitis B virus (HBV) is the commonest mode of infection and can be prevented with immunoprophylaxis of the infant and antiviral therapy in the mother. Our aim was to review a cohort of subjects with HBV in pregnancy to determine the prevalence of active disease or high HBV-DNA levels that required treatment to prevent transmission, and to review the management of mothers and infants.

Methods

A retrospective case-note review was conducted of all the HBV-infected pregnant women and their infants who attended the Newcastle obstetric services from 2007 to 2011.

Results

There were 113 pregnancies in 81 women (median age 28 years; 15% hepatitis B e antigen (HBeAg) positive) during 2007–11. 71% of mothers were first diagnosed with HBV during pregnancy. The mothers were born in 28 different countries. 69% of mothers had an HBV-DNA level less than 2000 IU/mL and 13% had HBV-DNA levels greater than 1.0×107 IU/mL so would be eligible for antiviral therapy to prevent transmission to the infant. 9% had active eAg-positive HBV and 3% had active eAg-negative HBV requiring treatment. All infants born to HBeAg-positive mothers received hepatitis B immunoglobulin (HBIG) appropriately and 76% of infants received a full HBV vaccination course. One infant born to an HBeAg-negative mother was hepatitis B surface antigen positive 1 year post-delivery.

Conclusions

One in six women had active HBV requiring treatment or high HBV-DNA levels that would benefit from antiviral treatment to reduce the transmission risk. HBIG was administered appropriately but completion of the vaccination course was suboptimal.
RADIATIVE NEUTRON CAPTURE ON 9Be, 14C, 14N, 15N AND 16O AT THERMAL AND ASTROPHYSICAL ENERGIES
Authors: DUBOVICHENKO SERGEY , DZHAZAIROV-KAKHRAMANOV ALBERT , AFANASYEVA NADEZHDA
Published: October 2013

The total cross-sections of the radiative neutron capture processes on 9 Be , 14 C , 14 N , 15 N and 16 O are described in the framework of the modified potential cluster model with the classification of orbital states according to Young tableaux. The continued interest in the study of these reactions is due, on the one hand, to the important role played by this process in the analysis of many fundamental properties of nuclei and nuclear reactions, and, on the other hand, to the wide use of the capture cross-section data in the various applications of nuclear physics and nuclear astrophysics, and, also, to the importance of the analysis of primordial nucleosynthesis in the Universe. This article is devoted to the description of results for the processes of the radiative neutron capture on certain light atomic nuclei at thermal and astrophysical energies. The considered capture reactions are not part of stellar thermonuclear cycles, but involve in the reaction chains of inhomogeneous Big Bang models.
GROUND STATE MAGNETIC PROPERTIES OF ODD NEUTRON DY ISOTOPES
Authors: YAKUT HAKAN , TABAR EMRE , KULIEV ALI AKBAR , ZENGINERLER ZEMINE , KAPLAN PINAR
Published: October 2013

Using the quasiparticle phonon nuclear model (QPNM) and taking into account the spin–spin interaction, the effects of the spin polarization on spin gyromagnetic factors (gs) as well as the intrinsic magnetic moments (gK) of the deformed odd neutron155-165Dy isotopes were studied. The calculated values of gsand gKare in fair agreement with the experiment as well as with other microscopic calculations. Our calculations indicated that because of the core polarization, the gsfactors of the nucleons in the nucleus reduce noticeably from its free nucleon value and the spin–spin interactions play an important role in the explanation of the quenching of the gsfactors. A very good reproduction of the phenomenological quenching of gsfactor from its free values [Formula: see text] is obtained for155-165Dy .
Who's really in control: microbial regulation of protein trafficking in the epithelium
Authors: Hendricks Matthew R. , Bomberger Jennifer M.
Published: October 2013

Due to evolutionary pressure, there are many complex interactions at the interface between pathogens and eukaryotic host cells wherein host cells attempt to clear invading microorganisms and pathogens counter these mechanisms to colonize and invade host tissues. One striking observation from studies focused on this interface is that pathogens have multiple mechanisms to modulate and disrupt normal cellular physiology to establish replication niches and avoid clearance. The precision by which pathogens exert their effects on host cells makes them excellent tools to answer questions about cell physiology of eukaryotic cells. Furthermore, an understanding of these mechanisms at the host-pathogen interface will benefit our understanding of how pathogens cause disease. In this review, we describe a few examples of how pathogens disrupt normal cellular physiology and protein trafficking at epithelial cell barriers to underscore how pathogens modulate cellular processes to cause disease and how this knowledge has been utilized to learn about cellular physiology.
Physical Biology in Cancer. 3. The role of cell glycocalyx in vascular transport of circulating tumor cells
Authors: Mitchell Michael J. , King Michael R.
Published: October 2013

Circulating tumor cells (CTCs) in blood are known to adhere to the luminal surface of the microvasculature via receptor-mediated adhesion, which contributes to the spread of cancer metastasis to anatomically distant organs. Such interactions between ligands on CTCs and endothelial cell-bound surface receptors are sensitive to receptor-ligand distances at the nanoscale. The sugar-rich coating expressed on the surface of CTCs and endothelial cells, known as the glycocalyx, serves as a physical structure that can control the spacing and, thus, the availability of such receptor-ligand interactions. The cancer cell glycocalyx can also regulate the ability of therapeutic ligands to bind to CTCs in the bloodstream. Here, we review the role of cell glycocalyx on the adhesion and therapeutic treatment of CTCs in the bloodstream.
Physical Biology in Cancer. 4. Physical cues guide tumor cell adhesion and migration
Authors: Stroka Kimberly M. , Konstantopoulos Konstantinos
Published: October 2013

As tumor cells metastasize from the primary tumor location to a distant secondary site, they encounter an array of biologically and physically heterogeneous microenvironments. While it is well established that biochemical signals guide all stages of the metastatic cascade, mounting evidence indicates that physical cues also direct tumor cell behavior, including adhesion and migration phenotypes. Physical cues acting on tumor cells in vivo include extracellular matrix mechanical properties, dimensionality, and topography, as well as interstitial flow, hydrodynamic shear stresses, and local forces due to neighboring cells. State-of-the-art technologies have recently enabled us and other researchers to engineer cell microenvironments that mimic specific physical properties of the cellular milieu. Through integration of these engineering strategies, along with physics, molecular biology, and imaging techniques, we have acquired new insights into tumor cell adhesion and migration mechanisms. In this review, we focus on the extravasation and invasion stages of the metastatic cascade. We first discuss the physical role of the endothelium during tumor cell extravasation and invasion and how contractility of endothelial and tumor cells contributes to the ability of tumor cells to exit the vasculature. Next, we examine how matrix dimensionality and stiffness coregulate tumor cell adhesion and migration beyond the vasculature. Finally, we summarize how tumor cells translate and respond to physical cues through mechanotransduction. Because of the critical role of tumor cell mechanotransduction at various stages of the metastatic cascade, targeting signaling pathways involved in tumor cell mechanosensing of physical stimuli may prove to be an effective therapeutic strategy for cancer patients.
Fiber atrophy, oxidative stress, and oxidative fiber reduction are the attributes of different phenotypes in chronic obstructive pulmonary disease patients
Authors: Gouzi Fares , Abdellaoui Aldjia , Molinari Nicolas , Pinot Edith , Ayoub Bronia , Laoudj-Chenivesse Dalila , Cristol Jean-Paul , Mercier Jacques , Hayot Maurice , Préfaut Christian
Published: October 2013

Peripheral muscle dysfunction, associated with reductions in fiber cross-sectional area (CSA) and in type I fibers, is a key outcome in chronic obstructive pulmonary disease (COPD). However, COPD peripheral muscle function and structure show great heterogeneity, overlapping those in sedentary healthy subjects (SHS). While discrepancies in the link between muscle structure and phenotype remain unexplained, we tested whether the fiber CSA and the type I fiber reductions were the attributes of different phenotypes of the disease, using unsupervised clustering method and post hoc validation. Principal component analysis performed on functional and histomorphological parameters in 64 COPD patients {forced expiratory volume in 1 s (FEV1) = 42.0 [30.0–58.5]% predicted} and 27 SHS (FEV1 = 105.0 [95.0–114.0]% predicted) revealed two COPD clusters with distinct peripheral muscle dysfunctions. These two clusters had different type I fiber proportion (26.0 ± 14.0% vs. 39.8 ± 12.6%; P < 0.05), and fiber CSA (3,731 ± 1,233 vs. 5,657 ± 1,098 μm2; P < 0.05). The “atrophic” cluster showed an increase in muscle protein carbonylation (131.5 [83.6–200.3] vs. 83.0 [68.3–105.1]; P < 0.05). Then, COPD patients underwent pulmonary rehabilitation. If the higher risk of exacerbations in the “atrophic” cluster did not reach statistical significance after adjustment for FEV1 (hazard ratio: 2.43; P = 0.11, n = 54), the improvement of VO2sl after training was greater than in the nonatrophic cluster (+24 ± 16% vs. +6 ± 13%; P < 0.01). Last, their age was similar (60.4 ± 8.8 vs. 60.8 ± 9.0 yr; P = 0.87), suggesting a different time course of the disease. We identified and validated two phenotypes of COPD patients showing different muscle histomorphology and level of oxidative stress. Thus our study demonstrates that the muscle heterogeneity is the translation of different phenotypes of the disease.
Brain stem serotonin protects blood pressure in neonatal rats exposed to episodic anoxia
Authors: Yang Hsiao T. , Cummings Kevin J.
Published: October 2013

In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)] in utero or at birth compromises anoxia-induced gasping and the recovery of heart rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT content is unknown. We hypothesized that a loss of 5-HT for ∼1 day would compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg ip) into rat pups (postnatal days 9–10 or 11–13, n = 22 treated, 24 control), causing a ∼70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15 anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In younger pups, we measured breathing frequency and tidal volume using “head-out” plethysmography and HR from the electrocardiogram. In older pups, we used whole body plethysmography to detect gasping, while monitoring MAP. Gasp latency and the time required for respiratory, HR, and MAP recovery following each episode were determined. Despite normal gasp latency, breathing frequency and a larger tidal volume ( P < 0.001), 5-HT-deficient pups survived one-half the number of episodes as controls ( P < 0.001). The anoxia-induced decrease in MAP experienced by 5-HT-deficient pups was double that of controls ( P = 0.017), despite the same drop in HR ( P = 0.48). MAP recovery was delayed ∼10 s by 5-HT deficiency ( P = 0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced, premature loss of MAP in response to episodic anoxia. These data may help explain why some sudden infant death syndrome cases die from what appears to be cardiovascular collapse during apparent severe hypoxia.
A Heterodimeric Fc-Based Bispecific Antibody Simultaneously Targeting VEGFR-2 and Met Exhibits Potent Antitumor Activity
Authors: Choi Hye-Ji , Kim Ye-Jin , Lee Sangho , Kim Yong-Sung
Published: October 2013

Heterodimeric Fc designed by engineering the CH3 homodimeric interface of immunoglobulin G1 serves as an attractive scaffold for the generation of bispecific antibodies (bsAb) due to the favorable properties of the Fc region. In this study, we describe a heterodimeric Fc generated by substituting the conserved electrostatic interactions at the CH3 core interface with asymmetric hydrophobic interactions and introducing asymmetric, long-range electrostatic interactions at the rim of the CH3 interface. Coexpression of Fc proteins carrying the combined CH3 variant pairs in HEK293F cells produced the heterodimer, which was purified with more than 90% yield, and retained wild-type Fc biophysical properties. The heterodimeric Fc was exploited to generate a bsAb simultaneously targeting both the Met receptor tyrosine kinase and the VEGF receptor 2 (VEGFR-2), with two respective antigen-specific, single-chain variable fragments (scFv) into the N-terminus. The Met × VEGFR-2 bsAb bound concurrently to the two target antigens, efficiently inhibited the downstream signaling and tube formation stimulated by the two receptors in human endothelial cells, and exhibited more potent antitumor efficacy in MKN45 human gastric cancer xenograft models than both the parent monospecific antibody alone. Collectively, based on the newly designed heterodimeric Fc-based bsAb, our results provide the therapeutic potential of bsAb targeting both Met and VEGFR-2 simultaneously for the treatment of human cancers. Mol Cancer Ther; 12(12); 2748–59. ©2013 AACR.
Generation and Analysis of Draft Sequences of ‘Stolbur' Phytoplasma from Multiple Displacement Amplification Templates
Authors: Mitrović Jelena , Siewert Christin , Duduk Bojan , Hecht Jochen , Mölling Karin , Broecker Felix , Beyerlein Peter , Büttner Carmen , Bertaccini Assunta , Kube Michael
Published: October 2013

Phytoplasma-associated diseases are reported for more than 1,000 plant species worldwide. Only a few genome sequences are available in contrast to the economical importance of these bacterial pathogens. A new strategy was used to retrieve phytoplasma strain-specific genome data. Multiple displacement amplification was performed on DNA obtained from <3 g of plant tissue from tobacco and parsley samples infected with ‘stolbur' strains. Random hexamers and Phi29 polymerase were evaluated with and without supplementation by group-assigned oligonucleotides providing templates for Illumina's sequencing approach. Metagenomic drafts derived from individual and pooled strain-specific de novo assemblies were analyzed. Supplementation of the Phi29 reaction with the group-assigned oligonucleotides resulted in an about 2-fold enrichment of the percentage of phytoplasma-assigned reads and thereby improved assembly results. The obtained genomic drafts represent the largest datasets available from ‘stolbur' phytoplasmas. Sequences of the two strains (558 kb, 448 proteins and 516 kb, 346 proteins, respectively) were annotated allowing the identification of prominent membrane proteins and reconstruction of core pathways. Analysis of a putative truncated sucrose phosphorylase provides hints on sugar degradation. Furthermore, it is shown that drafts obtained from repetitive-rich genomes allow only limited analysis on multicopy regions and genome completeness.
Analysis of the Complete Genomes of Acholeplasma brassicae, A. palmae and A. laidlawii and Their Comparison to the Obligate Parasites from ‘Candidatus Phytoplasma'
Authors: Kube Michael , Siewert Christin , Migdoll Alexander M. , Duduk Bojan , Holz Sabine , Rabus Ralf , Seemüller Erich , Mitrovic Jelena , Müller Ines , Büttner Carmen , Reinhardt Richard
Published: October 2013

Analysis of the completely determined genomes of the plant-derived Acholeplasma brassicae strain O502 and A. palmae strain J233 revealed that the circular chromosomes are 1,877,792 and 1,554,229 bp in size, have a G + C content of 36 and 29%, and encode 1,690 and 1,439 proteins, respectively. Comparative analysis of these sequences and previously published genomes of A. laidlawii strain PG-8, ‘Candidatus Phytoplasma asteris' strains, ‘Ca. P. australiense' and ‘Ca. P. mali' show a limited shared basic genetic repertoire. The acholeplasma genomes are characterized by a low number of rearrangements, duplication and integration events. Exceptions are the unusual duplication of rRNA operons in A. brassicae and an independently introduced second gene for a single-stranded binding protein in both genera. In contrast to phytoplasmas, the acholeplasma genomes differ by encoding the cell division protein FtsZ, a wide variety of ABC transporters, the F₀F1 ATP synthase, the Rnf-complex, SecG of the Sec-dependent secretion system, a richly equipped repertoire for carbohydrate metabolism, fatty acid, isoprenoid and partial amino acid metabolism. Conserved metabolic proteins encoded in phytoplasma genomes such as the malate dehydrogenase SfcA, several transporters and proteins involved in host-interaction, and virulence-associated effectors were not predicted for the acholeplasmas.
In vivo Diagnosis of Basal Cell Carcinoma Subtype by Reflectance Confocal Microscopy
Authors: Peppelman Malou , Wolberink Esther A.W. , Blokx Willeke A.M. , van de Kerkhof Peter C.M. , van Erp Piet E.J. , Gerritsen Marie-Jeanne P.
Published: October 2013

Background: Reflectance confocal microscopy (RCM) is a noninvasive imaging technique. Currently, RCM is mainly used for the diagnosis of melanoma and nonmelanoma skin cancer including basal cell carcinoma (BCC). Until now, it has not been possible to distinguish between subtypes of BCC using RCM. Objective: To establish the RCM features for subtypes of BCC. Methods: 57 lesions were selected for RCM imaging. Clinical and dermatoscopic pictures were taken and a 3-mm biopsy was obtained. Results: It was demonstrated that tumor nests with peripheral palisading, branch-like structures, fibrotic septa and increase in vascular diameter were characteristic RCM features for nodular and micronodular BCC. The size and shape of the tumor nests allowed further distinction between these BCCs. Solar elastosis and tumor nests connected with the basal cell layer characterize superficial BCC. Conclusion: This study presents RCM features for BCC, which might allow in vivo diagnosis of the nodular, micronodular and superficial subtype of BCC. This could prevent a skin biopsy, resulting in direct proper treatment. Further, RCM allows to evaluate the total lesion, which makes it possible to detect mixed-type BCCs.
Isolation and Chondrogenic Differentiation of Porcine Perichondrial Progenitor Cells for the Purpose of Cartilage Tissue Engineering
Authors: Derks Mareike , Sturm Theresa , Haverich Axel , Hilfiker Andres
Published: October 2013

In vivo, cartilage has a limited regenerative capacity. Clinical replacement strategies require a suitable cell source to provide a stable chondrocyte phenotype without hypertrophic cartilage development, while being broadly available, and harboring a high proliferative potential. Thus, the aim of this study was to analyze the proliferation and chondrogenic differentiation capacity of porcine perichondrial progenitor cells (PPC) isolated from auricular (ePPC) and tracheal cartilage (tPPC) as an alternative cell source to mesenchymal stem cells (MSC). The proliferative potential of these cell types was analyzed by means of doubling times. Cell pellets were cultured in chondrogenic differentiation medium for 4 weeks. Potential chondrogenic differentiation was investigated by histology and immunohistology in addition to gene expression analysis of the cartilage markers collagen II, aggrecan, cartilage oligomeric matrix protein (COMP), the precartilage marker collagen I, and the hypertrophic cartilage marker collagen X. PPC showed a proliferative behavior comparable to that of MSC. Chondrogenic stimulation resulted in a higher expression of collagen II, aggrecan, and COMP in ePPC as compared to tPPC and MSC, whereas the expression of collagen I was comparable in all cell types independently of differentiation stimulation. Collagen type X, however, could not be detected. The production of cartilage-like extracellular matrix components in PPC pellets was confirmed by histological and immunohistological stains. Elastin, a component of auricular cartilage, however, was not detected in ePPC-derived pellets. Thus, PPC present a promising cell source for tissue engineering of cartilage. Furthermore, ePPC may be more convenient than tPPC due to their higher chondrogenic potential and better accessibility.
Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment
Authors: de Boer J. Daan , Yang Jack , van den Boogaard Florry E. , Hoogendijk Arie J. , de Beer Regina , van der Zee Jaring S. , Roelofs Joris J.T.H. , van 't Veer Cornelis , de Vos Alex F. , van der Poll Tom
Published: October 2013

Background: Mast cells are implicated in allergic and innate immune responses in asthma, although their role in models using an allergen relevant for human disease is incompletely understood. House dust mite (HDM) allergy is common in asthma patients. Our aim was to investigate the role of mast cells in HDM-induced allergic lung inflammation. Methods: Wild-type (Wt) and mast cell-deficient Kitw-sh mice on a C57BL/6 background were repetitively exposed to HDM via the airways. Results: HDM challenge resulted in a rise in tryptase activity in bronchoalveolar lavage fluid (BALF) of Wt mice, indicative of mast cell activation. Kitw-sh mice showed a strongly attenuated HDM- induced recruitment of eosinophils in BALF and lung tissue, accompanied by reduced pulmonary levels of the eosinophil chemoattractant eotaxin. Remarkably, Kitw-sh mice demonstrated an unaltered capacity to develop lung pathology and increased mucus production in response to HDM. The increased plasma IgE in response to HDM in Wt mice was absent in Kitw-sh mice. Conclusion: These data contrast with previous reports on the role of mast cells in models using ovalbumin as allergen in that C57BL/6 Kitw-sh mice display a selective impairment of eosinophil recruitment without differences in other features of allergic inflammation.
Failure of Fourth-Generation Enzyme Immunoassay in HIV Screening and Plasma HIV-1 RNA Detection in Recent High-Risk Behavior
Authors: Maylin Sarah , Fouéré Sébastien , Simon François , Delaugerre Constance
Published: October 2013

Acute HIV infection was not detected in a young man presenting symptoms of sexual disease infection using fourth-generation screening tests combining HIV-specific antibody and p24 antigen. Detection of plasma HIV-1 RNA concomitant with screening tests may be proposed in individuals presenting with a symptomatic sexually transmitted infection.
Hedgehog-Dependent Regulation of Angiogenesis and Myogenesis Is Impaired in Aged Mice
Authors: Renault Marie-Ange , Robbesyn Fanny , Chapouly Candice , Yao Qinyu , Vandierdonck Soizic , Reynaud Annabel , Belloc Isabelle , Traiffort Elisabeth , Ruat Martial , Desgranges Claude , Gadeau Alain-Pierre
Published: October 2013

Objective—

The purpose of this study is to further document alteration of signal transduction pathways, more particularly of hedgehog (Hh) signaling, causing impaired ischemic muscle repair in old mice.

Approach and Results—

We used 12-week-old (young mice) and 20- to 24-month-old C57BL/6 mice (old mice) to investigate the activity of Hh signaling in the setting of hindlimb ischemia–induced angiogenesis and skeletal muscle repair. In this model, delayed ischemic muscle repair observed in old mice was associated with an impaired upregulation of Gli1. Sonic Hh expression was not different in old mice compared with young mice, whereas desert Hh (Dhh) expression was downregulated in the skeletal muscle of old mice both in healthy and ischemic conditions. The rescue of Dhh expression by gene therapy in old mice promoted ischemia-induced angiogenesis and increased nerve density; nevertheless, it failed to promote myogenesis or to increase Gli1 mRNA expression. After further investigation, we found that, in addition to Dhh, smoothened expression was significantly downregulated in old mice. We used smoothened haploinsufficient mice to demonstrate that smoothened knockdown by 50% is sufficient to impair activation of Hh signaling and ischemia-induced muscle repair.

Conclusions—

The present study demonstrates that Hh signaling is impaired in aged mice because of Dhh and smoothened downregulation. Moreover, it shows that hegdehog-dependent regulation of angiogenesis and myogenesis involves distinct mechanisms.
Characterization of Catheter–Tissue Contact Force During Epicardial Radiofrequency Ablation in an Ovine Model
Authors: Wong Michael C.G. , Edwards Glenn , Spence Steven J. , Kalman Jonathan M. , Kumar Saurabh , Joseph Stephen A. , Morton Joseph B.
Published: October 2013

Background—

Contact force (CF) during radiofrequency ablation (RFA) is an important determinant of endocardial lesion size with limited data on epicardial RFA and CF. We evaluated CF characteristics using irrigated RFA on the epicardium in an ovine model.

Methods and Results—

In 12 sheep, a 7-F irrigated RFA catheter with CF sensor was introduced via a pericardial incision onto/in parallel with ventricular epicardium. RFA (30 W per 30 second duration) was applied at 5
g
, 10
g
, 20
g
, 40
g
, and 70
g
: (1) over left and right ventricular myocardium with or without fat, (2) either directly over or adjacent to a coronary artery, or directly over the phrenic nerve. Force–time integral, lesion dimensions, and coronary artery/phrenic nerve injury were recorded. Lesion size, volume, and force–time integral progressively increased with higher CF (
P
<0.05). Steam pops occurred with high CF. Epicardial fat had an attenuating effect on RF penetration into myocardium (
P
<0.05); however, myocardial RF lesions could be created at sites with >3.5 mm epicardial fat. At sites with epicardial fat, each 10
g
increment in CF led to a 0.6 mm increase in lesion depth, whereas each 1 mm of fat reduced lesion depth into underlying myocardium by 0.7 mm. Extent of acute coronary injury with direct and indirect RFA and phrenic nerve palsy occurrence was proportional to CF.

Conclusions—

CF is a determinant of epicardial RF lesion size, steam pops, acute coronary artery injury, and phrenic nerve injury. Although epicardial fat limits lesion size, RFA with high CF can produce small myocardial RF lesions at sites of thick epicardial fat.
Relationship Between Gap-Junctional Conductance and Conduction Velocity in Mammalian Myocardium
Authors: Dhillon Paramdeep S. , Gray Rosaire , Kojodjojo Pipin , Jabr Rita , Chowdhury Rasheda , Fry Christopher H. , Peters Nicholas S.
Published: October 2013

Background—

Gap junction resistivity,
R
j
, has been proposed as a key determinant of conduction velocity (CV). However, studies in connexin-gene knockout mice demonstrated significant CV slowing only with near-complete connexin deletion, and these findings led to the concept of a significant redundancy of myocardial gap junctions. We challenged this prevailing concept and addressed the hypothesis that there is a continuous relationship between
R
j
and CV, each independently measured in human and guinea-pig myocardium.

Methods and Results—

R
j
and CV were directly measured by oil-gap impedance and microelectrode techniques in human left ventricular myocardium from patients with hypertrophic cardiomyopathy and in guinea-pig atrial and ventricular myocardium before and during pharmacological uncoupling with 20-µmol/L carbenoxolone. There was a continuous relationship between
R
j
and CV in human and guinea-pig myocardium, pre- and post-carbenoxolone (
r
2
=0.946;
P
<0.01). In guinea-pig left ventricle, left atrium, and right atrium, carbenoxolone increased
R
j
by 28±9%, 26±16%, and 25±14% and slowed CV by 17±3%, 23±8%, and 11±4% respectively (all
P
<0.05 versus control). As a clinically accessible measure of local microscopic myocardial conduction slowing in vivo in the intact human heart, carbenoxolone prolonged electrogram duration in the right atrium (39.7±4.2 to 42.3±4.3 ms;
P
=0.01) and right ventricle (48.1±2.5 to 53.3±5.3 ms;
P
<0.01).

Conclusions—

There is a continuous relationship between
R
j
and CV that is consistent between cardiac chambers and across species, indicating that naturally occurring variations in cellular coupling can account for variations in CV, and that the concept that there is massive redundancy of coupling is not tenable.
Chronic Akt1 Deficiency Attenuates Adverse Remodeling and Enhances Angiogenesis After Myocardial Infarction
Authors: Vandoorne Katrien , Vandsburger Moriel H. , Raz Tal , Shalev Moran , Weisinger Karen , Biton Inbal , Brumfeld Vlad , Raanan Calanit , Nevo Nava , Eilam Raya , Hemmings Brian A. , Tzahor Eldad , Harmelin Alon , Gepstein Lior , Neeman Michal
Published: October 2013

Background—

Akt1 is a key signaling molecule in multiple cell types, including endothelial cells. Accordingly, Akt1 was proposed as a therapeutic target for ischemic injury in the context of myocardial infarction (MI). The aim of this study was to use multimodal in vivo imaging to investigate the impact of systemic Akt1 deficiency on cardiac function and angiogenesis before and after MI.

Methods and Results—

In vivo cardiac MRI was performed before and at days 1, 8, 15, and 29 to 30 after MI induction for wild-type, heterozygous, and Akt1-deficient mice. Noninfarcted hearts were imaged using ex vivo stereomicroscopy and microcomputed tomography. Histological examination was performed for noninfarcted hearts and for hearts at days 8 and 29 to 30 after MI. MRI revealed mildly decreased baseline cardiac function in Akt1 null mice, whereas ex vivo stereomicroscopy and microcomputed tomography revealed substantially reduced coronary macrovasculature. After MI, Akt1
–/–
mice demonstrated significantly attenuated ventricular remodeling and a smaller decrease in ejection fraction. At 8 days after MI, a larger functional capillary network at the remote and border zone, accompanied by reduced scar extension, preserved cardiac function, and enhanced border zone wall thickening, was observed in Akt1
–/–
mice when compared with littermate controls.

Conclusions—

Using multimodal imaging to probe the role of Akt1 in cardiac function and remodeling after MI, this study revealed reduced adverse remodeling in Akt1-deficient mice after MI. Augmented myocardial angiogenesis coupled with a more functional myocardial capillary network may facilitate revascularization and therefore be responsible for preservation of infarcted myocardium.
Australian Public’s Awareness of Stroke Warning Signs Improves After National Multimedia Campaigns
Authors: Bray Janet E. , Johnson Roslyn , Trobbiani Kym , Mosley Ian , Lalor Erin , Cadilhac Dominique
Published: October 2013

Background and Purpose—

The aim of this study was to examine the reach and impact of the National Stroke Foundation (NSF) multimedia stroke warning sign campaigns across Australia.

Methods—

A total of 12 439 surveys were performed across 6 states during 6 years on random state–weighted samples of Australians ≥40 years old.

Results—

Awareness of stroke advertising increased 31% to 50% between 2004 and 2010 (
P
<0.001), as did the unprompted recall of ≥2 most common stroke warning signs 20% to 53% (
P
<0.001). Awareness of stroke advertising was independently associated with recalling ≥2 common signs (adjusted odds ratio=1.88, 95% confidence interval [1.74–2.04];
P
<0.001). Awareness was not greater in respondents with previous stroke or risk factors, except atrial fibrillation.

Conclusions—

The Australian public’s awareness of stroke warning signs has improved since commencement of the NSF campaigns commensurate with greater awareness of stroke advertising. Public education efforts are worthwhile, and future efforts should focus on groups identified with low awareness or those at high risk of stroke.
Effects of MLC601 on Early Vascular Events in Patients After Stroke
Authors: Chen Christopher L.H. , Venketasubramanian Narayanaswamy , Lee Chun Fan , Wong K.S. Lawrence , Bousser Marie-Germaine ,   CHIMES Study Investigators,   Philippines, Navarro Jose C. , Gan Herminigildo H. , Lao Annabelle Y. , Baroque Alejandro C. , Lokin Johnny , Hiyadan John Harold B. , Sarfati Ma. Socorro , Fangonillo Randolph John , Ambasing Neil , Chua Carlos L. , San Jose Ma. Cristina , Advincula Joel M. , Berame Eli John , Canete Maria Teresa ,   Singapore, Venketasubramanian Narayanaswamy , Young Sherry H.Y. , Mamauag Marlie Jane , Tay San San , Pande Shrikant , Thirugnanam Umapathi , Singh Rajinder , Chang Hui Meng , De Silva Deidre Anne , Chan Bernard P.L. , Sharma Vijay , Luen Teoh Hock ,   Thailand, Poungvarin Niphon , Muengtaweepongsa Sombat , Towanabut Somchai , Suwanwela Nijasri C. , Chotickanuchit Songkram , Chankrachang Siwaporn , Nitinun Samart ,   Sri Lanka, de Silva H. Asita , Ranawake Udaya , Wijekoon Nirmala ,   Hong Kong, Wong K.S. Lawrence ,   Malaysia, Eow Gaik Bee
Published: October 2013

Background and Purpose—

Early vascular events are an important cause of morbidity and mortality in the first 3 months after a stroke. We aimed to investigate the effects of MLC601 on the occurrence of early vascular events within 3 months of stroke onset.

Methods—

Post hoc analysis was performed on data from subjects included in the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study, a randomized, placebo-controlled, double-blinded trial that compared MLC601 with placebo in 1099 subjects with ischemic stroke of intermediate severity in the preceding 72 hours. Early vascular events were defined as a composite of recurrent stroke, acute coronary syndrome, and vascular death occurring within 3 months of stroke onset.

Results—

The frequency of early vascular events during the 3-month follow-up was significantly less in the MLC601 group than in the placebo group (16 [2.9%] versus 31 events [5.6%]; risk difference=−2.7%; 95% confidence interval, −5.1% to −0.4%;
P
=0.025) without an increase in nonvascular deaths. Kaplan–Meier survival analysis showed a difference in the risk of vascular outcomes between the 2 groups as early as the first month after stroke (Log-rank
P
=0.024; hazard ratio, 0.51; 95% confidence interval, 0.28–0.93).

Conclusions—

Treatment with MLC601 was associated with reduced early vascular events among subjects in the CHIMES study. The mechanisms for this effect require further study.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00554723.
Range expansion of Ponto-Caspian mysids (Mysida, Mysidae) in the River Tisza: first record of Paramysis lacustris (Czerniavsky, 1882) for Hungary
Authors: Borza Péter , Boda Pál
Published: October 2013

In the River Tisza, the longest tributary of the Danube,Limnomysis benedeniCzerniavsky, 1882 had been the only mysid recorded until recently. In 2011, we found a few juvenile specimens ofHemimysis anomalaG. O. Sars, 1907 in two daytime samples taken from the Hungarian river section. During the overnight survey in 2012 aimed at revealing the actual distribution of this nocturnally active species, its most upstream occurrence was detected at Szolnok (river km 334).Paramysis lacustris(Czerniavsky, 1882) was also found at every sampling site of the river downstream of Tiszabercel (rkm 568), representing the first record of the species for the fauna of Hungary, and its most upstream self-sustaining population in the basin of the River Danube (1759 rkm from the Danube mouth).P. lacustrisis the fourth Ponto-Caspian mysid that has begun to expand its range spontaneously in the Danube catchment afterL. benedeni,H. anomala, andKatamysis warpachowskyiG. O. Sars, 1893. Due to its zooplanktivory it can be anticipated to have a considerable effect on the composition and abundance of the zooplankton assemblages and it may also become an important food source for certain fish species, especially in the impounded reaches and in stagnant or slow-flowing backwaters.P. lacustris — similarly toH. anomala — shows a diel vertical migration, moving to shallow waters only by night, which calls for increased attention in order to reveal its possible future range expansions. Although the River Tisza itself is not connected directly to other river basins via canals, it may potentially contribute to the further spread of the species (e.g., via fish stocking).
UV Sensitivity to Changes in Ozone, Aerosols, and Clouds in Seoul, South Korea
Authors: Kim Woogyung , Kim Jhoon , Park Sang Seo , Cho Hi-Ku
Published: October 2013

The total ozone (O3) and aerosol optical depth (AOD) at 320 nm have been observed from the ultraviolet (UV) measurements made at Yonsei University in Seoul, South Korea, with Dobson and Brewer spectrophotometers, respectively, during 2004–10. The daily datasets are analyzed to show the sensitivities of UV radiation to changes in O3, AOD, and cloud cover (CC) together with global solar radiation (GS), including the long-term characteristics of surface UV irradiance in Seoul. The UV sensitivities show that 1% increases of O3 and AOD relative to their reference values under all- and clear-sky conditions similarly manifest as 1–1.2% and 0.2% decreases of both daily erythemal UV (EUV) and total UV (TUV) irradiance at the ground level except for TUV sensitivity to O3 (~0.3%). Those UV sensitivities to CC and GS changes are associated with a 0.12% decrease and 0.7% increase, respectively, in fractional UV changes. The trends show that the positive trends of O3 (+7.2% decade−1), AOD (+22.4% decade−1), and CC (+52.4% decade−1) induce negative trends in EUV (−8.4% decade−1) and TUV (−2.5% decade−1), in both UV (−4.7% decade−1), and in EUV (−6.3% decade−1) and TUV (−6.8% decade−1), respectively. On the basis of the multiple linear regression analyses, it is found that UV sensitivity to O3 is relatively high in the forcing factors, but the contributions of the UV forcing factors to the daily variability and the range of UV disturbances due to the variability of the forcing factors are affected more by AOD than by O3 and CC in both UV fractional changes.
A Heuristic Model of Dansgaard–Oeschger Cycles. Part I: Description, Results, and Sensitivity Studies
Authors: Singh Hansi A. , Battisti David S. , Bitz Cecilia M.
Published: October 2013

A simple model for studying the Dansgaard–Oeschger (D-O) cycles of the last glacial period is presented, based on the T. Dokken et al. hypothesis for D-O cycles. The model is a column model representing the Nordic seas and is composed of ocean boxes stacked below a one-layer sea ice model with an energy-balance atmosphere; no changes in the large-scale ocean overturning circulation are invoked. Parameterizations are included for latent heat polynyas and sea ice export from the column. The resulting heuristic model was found to cycle between stadial and interstadial states at times scales similar to those seen in the proxy observational data, with the presence or absence of perennial sea ice in the Nordic seas being the defining characteristic for each of these states. The major discrepancy between the modeled oscillations and the proxy record is in the length of the interstadial phase, which is shorter than that observed. The modeled oscillations were found to be robust to parameter changes, including those related to the ocean heat flux convergence (OHFC) into the column. Production of polynya ice was found to be an essential ingredient for such sustained oscillatory behavior. A simple parameterization of natural variability in the OHFC enhances the robustness of the modeled oscillations. The authors conclude by discussing the implications of such a hypothesis for the state of the Nordic seas today and its state during the Last Glacial Maximum and contrasting the model to other hypotheses that invoke large-scale changes in the Atlantic meridional overturning circulation for explaining millennial-scale variability in the climate system. An extensive time-scale analysis will be presented in the future.
Balanced and Coherent Climate Estimation by Combining Data with a Biased Coupled Model
Authors: Zhang S. , Chang Y.-S. , Yang X. , Rosati A.
Published: October 2013

Given a biased coupled model and the atmospheric and oceanic observing system, maintaining a balanced and coherent climate estimation is of critical importance for producing accurate climate analysis and prediction initialization. However, because of limitations of the observing system (e.g., most of the oceanic measurements are only available for the upper ocean), directly evaluating climate estimation with real observations is difficult. With two coupled models that are biased with respect to each other, a biased twin experiment is designed to simulate the problem. To do that, the atmospheric and oceanic observations drawn from one model based on the modern climate observing system are assimilated into the other. The model that produces observations serves as the truth and the degree by which an assimilation recovers the truth steadily and coherently is an assessment of the impact of the data constraint scheme on climate estimation. Given the assimilation model bias of warmer atmosphere and colder ocean, where the atmospheric-only (oceanic only) data constraint produces an overcooling (overwarming) ocean through the atmosphere–ocean interaction, the constraints with both atmospheric and oceanic data create a balanced and coherent ocean estimate as the observational model. Moreover, the consistent atmosphere–ocean constraint produces the most accurate estimate for North Atlantic Deep Water (NADW), whereas NADW is too strong (weak) if the system is only constrained by atmospheric (oceanic) data. These twin experiment results provide insights that consistent data constraints of multiple components are very important when a coupled model is combined with the climate observing system for climate estimation and prediction initialization.
Distance Velocity–Azimuth Display (DVAD)—New Interpretation and Analysis of Doppler Velocity
Authors: Lee Wen-Chau , Tang Xiaowen , Jou Ben J.-D.
Published: October 2013

The concept and mathematical framework of the distance velocity–azimuth display (DVAD) methodology is presented. DVAD uses rVd (Doppler velocity scaled by the distance from the radar to a gate, r) as the basis to display, interpret, and extract information from single Doppler radar observations. Both linear and nonlinear wind fields can be represented by the same Cartesian polynomial with different orders. DVAD is mathematically concise and superior to the velocity–azimuth display (VAD) in interpreting and deducing flow characteristics. The rVd pattern of a two-dimensional linear wind field is exclusively in the form of a bivariate quadratic equation representing conic sections (e.g., ellipse, parabola, and hyperbola) centered at the radar depending only on divergence and deformation. The presence of a constant background flow translates the conic sections to a different origin away from the radar. It is possible to graphically estimate the characteristics of a linear wind field from the conical sections without performing a VAD analysis. DVAD analysis can deduce quantitative flow characteristics by a least squares fitting and/or a derivative method, and is a natural way to account for nonlinearity. The rVd pattern behaves similar to a type of velocity potential in fluid mechanics where ∇(rVd) is a proxy of the true wind vector and is used to estimate the general flow pattern in the vicinity of the radar.
How Often Do Providers Discuss Asthma Action Plans With Children? Analysis of Transcripts of Medical Visits
Authors: Gillette Chris , Carpenter Delesha M. , Ayala Guadalupe X. , Williams Dennis M. , Davis Stephanie , Tudor Gail , Yeatts Karin , Sleath Betsy
Published: October 2013

Objective. To examine how often providers discussed asthma action plans with children and their caregivers and child, clinical, and provider characteristics that were associated with those discussions. Method. This was a cross-sectional analysis of audio-recorded visits between 35 general pediatric providers and 260 children (8-16 years old) with asthma and their caregivers. The visits were transcribed into text. The transcripts were coded for discussions about written asthma action plans. Results. Providers discussed written asthma action plans with 21.0% of children and caregivers. Providers were significantly more likely to discuss asthma action plans when the child was enrolled in Medicaid, the visit was asthma related, the visit was longer, the provider was not White, or more provider education. Conclusion. In our sample, providers rarely discussed action plans with children and their caregivers. Providers should discuss asthma action plans with every child with persistent asthma and their caregivers and revise them regularly.
Dealing With Omitted and Not-Reached Items in Competence Tests
Authors: Pohl Steffi , Gräfe Linda , Rose Norman
Published: October 2013

Data from competence tests usually show a number of missing responses on test items due to both omitted and not-reached items. Different approaches for dealing with missing responses exist, and there are no clear guidelines on which of those to use. While classical approaches rely on an ignorable missing data mechanism, the most recently developed model-based approaches account for nonignorable missing responses. Model-based approaches include the missing propensity in the measurement model. Although these models are very promising, the assumptions made in these models have not yet been tested for plausibility in empirical data. Furthermore, studies investigating the performance of different approaches have only focused on one kind of missing response at once. In this study, we investigated the performance of classical and model-based approaches in empirical data, accounting for different kinds of missing responses simultaneously. We confirmed the existence of a unidimensional tendency to omit items. Indicating nonignorability of the missing mechanism, missing tendency due to both omitted and not-reached items correlated with ability. However, results on parameter estimation showed that ignoring missing responses was sufficient to account for missing responses, and that the missing propensity was not needed in the model. The results from the empirical study were corroborated in a complete case simulation.
Neighborhood Built Environment, Perceived Danger, and Perceived Social Cohesion
Authors: Bjornstrom Eileen E. S. , Ralston Margaret L.
Published: October 2013

We examined whether the prevalence of commercial diversity, heavy traffic, sidewalks, and trees is associated with perceived social cohesion in Los Angeles County neighborhoods, and how concentrated disadvantage and perceived danger shape these relationships. Consistent with theoretical expectations, concentrated disadvantage and danger were associated with lower cohesion. The effects of built characteristics on cohesion were moderated by disadvantage and/or perceived danger. Danger moderated the effect of commercial diversity, sidewalks, and trees, and concentrated disadvantage moderated the coefficients on built variables (excepting trees) such that the magnitude of their effects were stronger in high-disadvantage neighborhoods. We conclude that built characteristics appear to matter more for cohesion in high-disadvantage neighborhoods and also that approaches to promoting cohesion through the built environment should focus on bolstering residents’ perceptions of safety.