bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling Gas Diffusion from Breaking Coal Samples with the Discrete Element Method
Authors: Lin Dan-Ling , Wang Yucang , Guo William W.
Published: February 2015

Particle scale diffusion is implemented in the discrete element code, Esys-Particle. We focus on the question of how to calibrate the particle scale diffusion coefficient. For the regular 2D packing, theoretical relation between micro- and macrodiffusion coefficients is derived. This relation is then verified in several numerical tests where the macroscopic diffusion coefficient is determined numerically based on the half-time of a desorption scheme. To further test the coupled model, we simulate the diffusion and desorption in the circular sample. The numerical results match the analytical solution very well. An example of gas diffusion and desorption during sample crushing and fragmenting is given at the last. The current approach is the first step towards a realistic and comprehensive modelling of coal and gas outbursts.
Ulam Problem for the Cosine Addition Formula in Sato Hyperfunctions
Authors: Chung Jaeyoung , Chung Soon-Yeong
Published: February 2015

We prove the Ulam problem for the cosine addition formula in the spaces of Schwartz distributions and Sato hyperfunctions with respect to bounded distributions and bounded hyperfunctions.
Alkaline Phosphatase in Stem Cells
Authors: Štefková Kateřina , Procházková Jiřina , Pacherník Jiří
Published: February 2015

Alkaline phosphatase is an enzyme commonly expressed in almost all living organisms. In humans and other mammals, determinations of the expression and activity of alkaline phosphatase have frequently been used for cell determination in developmental studies and/or within clinical trials. Alkaline phosphatase also seems to be one of the key markers in the identification of pluripotent embryonic stem as well as related cells. However, alkaline phosphatases exist in some isoenzymes and isoforms, which have tissue specific expressions and functions. Here, the role of alkaline phosphatase as a stem cell marker is discussed in detail. First, we briefly summarize contemporary knowledge of mammalian alkaline phosphatases in general. Second, we focus on the known facts of its role in and potential significance for the identification of stem cells.
Antenna Polarization Optimization for Target Detection in Non-Gaussian Clutter
Authors: Cheng Xu , Li Yong-zhen , Wang Xue-song
Published: February 2015

Adaptive polarization design of radar antenna has recently become the focus of attention in radar polarization community. A polarimetric detector against non-Gaussian clutter with transmitter polarization optimization has been proposed in this paper. First, the radar data model including the realistic dependence of the clutter on the transmitted polarization is introduced. Then the polarimetric detector with transmitter polarization optimization is developed. By employing the simulation, we demonstrate that the polarization waveform optimization can bring the significant performance gain on target detection as compared to the conventional full-polarization approach. Besides, jointly optimizing transmitter and receiver polarization to form a scalar measurement is confirmed not to achieve a better detection performance than vector measurement with only transmitter polarization optimization.
IgG4-Related Nasal Pseudotumor
Authors: Døsen L. K. , Jebsen P. , Dingsør B. , Haye R.
Published: February 2015

IgG4-related disease is recognized as one form of autoimmune pancreatitis. During the last ten years, it has also been described in several other organs. We present two patients with lesions showing a histological picture of fibrosis and lymphoplasmacytic infiltrations with abundant IgG4 positive plasma cells at hitherto unreported symmetrical nasal locations. The symmetrical complex consisted of one central lesion in the anterior nasal septum and the two others in each of the lateral nasal walls. The lesions extended from the anterior part of the inferior concha into the vestibulum and caused severe nasal obstruction.
A 3.9 μs Settling-Time Fractional Spread-Spectrum Clock Generator Using a Dual-Charge-Pump Control Technique for Serial-ATA Applications
Authors: Kawamoto Takashi , Suzuki Masato , Noto Takayuki
Published: February 2015

A low-jitter fractional spread-spectrum clock generator (SSCG) utilizing a fast-settling dual-charge-pump (CP) technique is developed for serial-advanced technology attachment (SATA) applications. The dual-CP architecture reduces a design area to 60% by shrinking an effective capacitance of a loop filter. Moreover, the settling-time is reduced by 4 μs to charge a current to the capacitor by only main-CP in initial period in settling-time. The SSCG is fabricated in a 0.13 μm CMOS and achieves settling time of 3.91 μs faster than 8.11 μs of a conventional SSCG. The random jitter and total jitter at 250 cycles at 1.5 GHz are less than 3.2 and 10.7 psrms, respectively. The triangular modulation signal frequency is 31.5 kHz and the modulation deviation is from −5000 ppm to 0 ppm at 1.5 GHz. The EMI reduction is 10.0 dB. The design area and power consumption are 300 × 700 μm and 18 mW, respectively.
Free Vibrations of a Series of Beams Connected by Viscoelastic Layers
Authors: Kelly S. Graham , Nicely Clint
Published: February 2015

An exact solution for free vibrations of a series of uniform Euler-Bernoulli beams connected by Kelvin-Voigt is developed. The beams have the same length and end conditions but can have different material or geometric properties. An example of five concentric beams connected by viscoelastic layers is considered.
A Translational, Pharmacodynamic, and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non–Small Cell Lung Cancer
Authors: Owonikoko Taofeek K. , Ramalingam Suresh S. , Miller Daniel L. , Force Seth D. , Sica Gabriel L. , Mendel Jennifer , Chen Zhengjia , Rogatko Andre , Tighiouart Mourad , Harvey R. Donald , Kim Sungjin , Saba Nabil F. , Pickens Allan , Behera Madhusmita , Fu Robert W. , Rossi Michael R. , Auffermann William F. , Torres William E. , Bechara Rabih , Deng Xingming , Sun Shi-Yong , Fu Haian , Gal Anthony A. , Khuri Fadlo R.
Published: February 2015

Purpose: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non–small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer.

Experimental Design: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls. Target modulation by everolimus was quantified in vivo and ex vivo by comparing metabolic activity on paired PET scans and expression of active phosphorylated forms of mTOR, Akt, S6, eIF4e, p70S6K, 4EBP1, and total Bim protein between pretreatment and posttreatment tissue samples.

Results: There were 23 patients on the treatment arm and 10 controls; median age 64 years; 22 tumors (67%) were adenocarcinomas. There was a dose-dependent reduction in metabolic activity (SUVmax: 29.0%, −21%, −24%; P = 0.014), tumor size (10.1%, 5.8%, −11.6%; P = 0.047), and modulation of S6 (−36.1, −13.7, −77.0; P = 0.071) and pS6 (−41.25, −61.57, −47.21; P = 0.063) in patients treated in the control, 5-mg, and 10-mg cohorts, respectively. Targeted DNA sequencing in all patients along with exome and whole transcriptome RNA-seq in an index patient with hypersensitive tumor was employed to further elucidate the mechanism of everolimus activity.

Conclusions: This “window-of-opportunity” study demonstrated measurable, dose-dependent, biologic, metabolic, and antitumor activity of everolimus in early-stage NSCLC. Clin Cancer Res; 21(8); 1859–68. ©2015 AACR.
Notch Reporter Activity in Breast Cancer Cell Lines Identifies a Subset of Cells with Stem Cell Activity
Authors: D'Angelo Rosemarie C. , Ouzounova Maria , Davis April , Choi Daejin , Tchuenkam Stevie M. , Kim Gwangil , Luther Tahra , Quraishi Ahmed A. , Senbabaoglu Yasin , Conley Sarah J. , Clouthier Shawn G. , Hassan Khaled A. , Wicha Max S. , Korkaya Hasan
Published: February 2015

Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch+) or reduced activity (Notch−) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch+ cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch+ cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch− cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch+ cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics. Mol Cancer Ther; 14(3); 779–87. ©2015 AACR.
Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2
Authors: Soares Heloisa P. , Ming Ming , Mellon Michelle , Young Steven H. , Han Liang , Sinnet-Smith James , Rozengurt Enrique
Published: February 2015

The PI3K/AKT/mTOR pathway, which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to drug resistance. Here, we demonstrate that treatment of PANC-1 or MiaPaCa-2 pancreatic ductal adenocarcinoma (PDAC) cells with the dual PI3K/mTOR kinase inhibitor (PI3K/TOR-KI) BEZ235 blocked mTORC1/S6K activation (scored by S6 phosphorylation at Ser240/244), mTORC1/4E-BP1 (assayed by 4E-BP1 phosphorylation at Thr37/46), and mTORC2-mediated AKT phosphorylation at Ser473, in a concentration-dependent manner. Strikingly, BEZ235 markedly enhanced the MEK/ERK pathway in a dose-dependent manner. Maximal ERK overactivation coincided with complete inhibition of phosphorylation of AKT and 4E-BP1. ERK overactivation was induced by other PI3K/TOR-KIs, including PKI-587 and GDC-0980. The MEK inhibitors U126 or PD0325901 prevented ERK overactivation induced by PI3K/TOR-KIs. The combination of BEZ235 and PD0325901 caused a more pronounced inhibition of cell growth than that produced by each inhibitor individually. Mechanistic studies assessing PI3K activity in single PDAC cells indicate that PI3K/TOR-KIs act through a PI3K-independent pathway. Doses of PI3K/TOR-KIs that enhanced MEK/ERK activation coincided with those that inhibited mTORC2-mediated AKT phosphorylation on Ser473, suggesting a role of mTORC2. Knockdown of RICTOR via transfection of siRNA markedly attenuated the enhancing effect of BEZ235 on ERK phosphorylation. We propose that dual PI3K/mTOR inhibitors suppress a novel negative feedback loop mediated by mTORC2, thereby leading to enhanced MEK/ERK pathway activity in pancreatic cancer cells. Mol Cancer Ther; 14(4); 1014–23. ©2015 AACR.
The IGF-Trap: Novel Inhibitor of Carcinoma Growth and Metastasis
Authors: Wang Ni , Rayes Roni F. , Elahi Seyyed Mehdy , Lu Yifan , Hancock Mark A. , Massie Bernard , Rowe Gerald E. , Aomari Hafida , Hossain Sazzad , Durocher Yves , Pinard Maxime , Tabariès Sébastien , Siegel Peter M. , Brodt Pnina
Published: February 2015

The IGFI receptor promotes malignant progression and has been recognized as a target for cancer therapy. Clinical trials with anti-IGFIR antibodies provided evidence of therapeutic efficacy but exposed limitations due in part to effects on, and the compensatory function of, the insulin receptor system. Here, we report on the production, characterization, and biologic activity of a novel, IGF-targeting protein (the IGF-Trap) comprising a soluble form of hIGFIR and the Fc portion of hIgG1. The IGF-Trap has a high affinity for hIGFI and hIGFII but low affinity for insulin, as revealed by surface plasmon resonance. It efficiently blocked IGFIR signaling in several carcinoma cell types and inhibited tumor cell proliferation, migration, and invasion in vitro. In vivo, the IGF-Trap showed favorable pharmacokinetic properties and could suppress the growth of established breast carcinoma tumors when administered therapeutically into tumor-bearing mice, improving disease-free survival. Moreover, IGF-Trap treatment markedly reduced experimental liver metastasis of colon and lung carcinoma cells, increasing tumor cell apoptosis and reducing angiogenesis. Finally, when compared with an anti-IGFIR antibody or IGF-binding protein-1 that were used at similar or higher concentrations, the IGF-Trap showed superior therapeutic efficacy to both inhibitors. Taken together, we have developed a targeted therapeutic molecule with highly potent anticancer effects that could address limitations of current IGFIR-targeting agents. Mol Cancer Ther; 14(4); 982–93. ©2015 AACR.
Functional Genetic Screen Identifies Increased Sensitivity to WEE1 Inhibition in Cells with Defects in Fanconi Anemia and HR Pathways
Authors: Aarts Marieke , Bajrami Ilirjana , Herrera-Abreu Maria T. , Elliott Richard , Brough Rachel , Ashworth Alan , Lord Christopher J. , Turner Nicholas C.
Published: February 2015

WEE1 kinase regulates CDK1 and CDK2 activity to facilitate DNA replication during S-phase and to prevent unscheduled entry into mitosis. WEE1 inhibitors synergize with DNA-damaging agents that arrest cells in S-phase by triggering direct mitotic entry without completing DNA synthesis, resulting in catastrophic chromosome fragmentation and apoptosis. Here, we investigated how WEE1 inhibition could be best exploited for cancer therapy by performing a functional genetic screen to identify novel determinants of sensitivity to WEE1 inhibition. Inhibition of kinases that regulate CDK activity, CHK1 and MYT1, synergized with WEE1 inhibition through both increased replication stress and forced mitotic entry of S-phase cells. Loss of multiple components of the Fanconi anemia (FA) and homologous recombination (HR) pathways, in particular DNA helicases, sensitized to WEE1 inhibition. Silencing of FA/HR genes resulted in excessive replication stress and nucleotide depletion following WEE1 inhibition, which ultimately led to increased unscheduled mitotic entry. Our results suggest that cancers with defects in FA and HR pathways may be targeted by WEE1 inhibition, providing a basis for a novel synthetic lethal strategy for cancers harboring FA/HR defects. Mol Cancer Ther; 14(4); 865–76. ©2015 AACR.
MAPK7 Regulates EMT Features and Modulates the Generation of CTCs
Authors: Javaid Sarah , Zhang Jianmin , Smolen Gromoslaw A. , Yu Min , Wittner Ben S. , Singh Anurag , Arora Kshitij S. , Madden Marissa W. , Desai Rushil , Zubrowski Matthew J. , Schott Benjamin J. , Ting David T. , Stott Shannon L. , Toner Mehmet , Maheswaran Shyamala , Shioda Toshi , Ramaswamy Sridhar , Haber Daniel A.
Published: February 2015

Epithelial-to-mesenchymal transition (EMT) has been implicated in models of tumor cell migration, invasion, and metastasis. In a search for candidate therapeutic targets to reverse this process, nontumorigenic MCF10A breast epithelial cells were infected with an arrayed lentiviral kinome shRNA library and screened for either suppression or enhancement of a 26-gene EMT RNA signature. No individual kinase gene knockdown was sufficient to induce EMT. In contrast, grouped epithelial markers were induced by knockdown of multiple kinases, including mitogen activated protein kinase 7 (MAPK7). In breast cancer cells, suppression of MAPK7 increased E-cadherin (CDH1) expression and inhibited cell migration. In an orthotopic mouse model, MAPK7 suppression reduced the generation of circulating tumor cells and the appearance of lung metastases. Together, these observations raise the possibility that targeting kinases that maintain mesenchymal cell properties in cancer cells, such as MAPK7, may lessen tumor invasiveness.

Implications: Suppression of MAPK7 induces epithelial markers, reduces generation of circulating tumor cells and appearance of lung metastases. Mol Cancer Res; 13(5); 934–43. ©2015 AACR.
Adenosine Receptor 2A Blockade Increases the Efficacy of Anti–PD-1 through Enhanced Antitumor T-cell Responses
Authors: Beavis Paul A. , Milenkovski Nicole , Henderson Melissa A. , John Liza B. , Allard Bertrand , Loi Sherene , Kershaw Michael H. , Stagg John , Darcy Phillip K.
Published: February 2015

Immunotherapy is rapidly emerging as a cancer treatment with high potential. Recent clinical trials with anti-CTLA-4 and anti–PD-1/PD-L1 antibodies (mAbs) suggest that targeting multiple immunosuppressive pathways may significantly improve patient survival. The generation of adenosine by CD73 also suppresses antitumor immune responses through the activation of A2A receptors on T cells and natural killer (NK) cells. We sought to determine whether blockade of A2A receptors could enhance the efficacy of anti–PD-1 mAb. The expression of CD73 by tumor cells limited the efficacy of anti–PD-1 mAb in two tumor models, and this was alleviated with concomitant treatment with an A2A adenosine receptor antagonist. The blockade of PD-1 enhanced A2A receptor expression on tumor-infiltrating CD8+ T cells, making them more susceptible to A2A-mediated suppression. Thus, dual blockade of PD-1 and A2A significantly enhanced the expression of IFNγ and Granzyme B by tumor-infiltrating CD8+ T cells and, accordingly, increased growth inhibition of CD73+ tumors and survival of mice. The results of our study indicate that CD73 expression may constitute a potential biomarker for the efficacy of anti–PD-1 mAb in patients with cancer and that the efficacy of anti–PD-1 mAb can be significantly enhanced by A2A antagonists. We have therefore revealed a potentially novel biomarker for the efficacy of anti–PD-1 that warrants further investigation in patients. Because our studies used SYN-115, a drug that has already undergone phase IIb testing in Parkinson disease, our findings have immediate translational relevance for patients with cancer. Cancer Immunol Res; 3(5); 506–17. ©2015 AACR.
Cutaneous Findings in Hemophagocytic Lymphohistiocytosis
Authors: Zerah Michele L. , DeWitt Christine A.
Published: February 2015

Background: Cutaneous findings associated with hemophagocytic lymphohistiocytosis (HLH) remain largely undescribed in the literature, yet are substantial and correlative with disease course. Objective: To catalog the clinical findings of cutaneous eruptions associated with HLH. Methods: We performed a retrospective chart review of patients meeting the criteria for HLH at two hospitals over 5 years. All patients meeting the criteria for HLH as defined by the HLH-2004 protocol were included. Results: Cutaneous lesions were categorized based on clinical presentations and histology. Lesions independent of immunocompromised state were observed, including pyoderma gangrenosum, panniculitis, morbilliform eruptions, Stevens-Johnson syndrome, atypical targetoid lesions and bullae. Histologic findings were non-specific. Conclusion: Cutaneous eruptions as a consequence of HLH are variable in presentation and identified as a diagnosis of exclusion. Findings are both primarily and secondarily induced by altered immunity. Further study is needed to allow better understanding of the immunopathogenesis involved.
Three-Dimensional Skin Models of Psoriasis
Authors: Soboleva Anna G. , Mezentsev Alexandre , Zolotorenko Alena , Bruskin Sergey , Pirusian Eleonora
Published: February 2015

Three-dimensional models of psoriatic skin occupy an intermediate position between cell cultures and animal-based models. Unlike cultured cells, they closely imitate changes in cell differentiation and metabolism, which are characteristic of psoriatic lesional skin. Because 3-dimensional models exclude nonspecific influences of the surrounding organs and tissues, in some studies they are preferred over animal-based models. Moreover, 3-dimensional models can be used for drug screening and testing new pharmacological approaches. In this paper, we discuss how 3-dimensional models of psoriatic lesional skin were created and developed. We also analyze their prospects in experimental studies of psoriasis.
Impact of Flow Cytometry in Liver Cytopathology
Authors: Bynum Jennifer P. , Duffield Amy , Ali Syed Z.
Published: February 2015

Background: Fine needle aspiration (FNA) is commonly used as a diagnostic tool for the evaluation of lymphoproliferative diseases. Cytomorphology alone is often insufficient for the diagnosis and subclassification of lymphoma; therefore, flow cytometry (FC) plays an important role in the characterization of lymphoproliferative disorders. This study reviews our experience with FC on liver FNA at the Johns Hopkins Hospital. Methods: 2,424 liver FNAs performed over a 21-year period were reviewed for clinical FC data (n = 74) or a subsequent diagnosis of lymphoma in the liver without FC data (n = 40). Results: In our study, 114 cases (4.7%) were included out of the 2,424 liver FNAs performed during the study period. Lymphoma was diagnosed 79 times. Cytomorphology alone was diagnostic of lymphoma in 45 cases, and in 33 cases both the cytomorphology and the FC were consistent with a diagnosis of lymphoma. Neither FC nor cytomorphology were diagnostic of lymphoma on 1 specimen. In 39 cases, FC had negative results on a lesion suspicious for lymphoma based on cytomorphology. In several nonlymphoma cases, FC provided information that allowed further subclassification of the neoplasm. Conclusion: FC is a useful adjuvant diagnostic test for liver FNAs performed on patients with lymphoproliferative disorders.
The Diagnostic Challenges of Autoimmune Pancreatitis
Authors: Papp Kata , Angst Eliane , Seidel Stefan , Flury-Frei Renata , Hetzer Franc Heinrich
Published: February 2015

Autoimmune pancreatitis is a rare but important differential diagnosis from pancreatic cancer. This autoimmune disease can mimic pancreatic cancer by its clinical symptoms, including weight loss and jaundice. Furthermore imaging findings may include a mass of the pancreas. Here we present the case of a 67-year-old male patient diagnosed with autoimmune pancreatitis but showing the well-known symptoms of pancreatic cancer. This emphasizes the difficulties of histological findings and the importance of the correct diagnostic process.
Early stent thrombosis with bivalirudin in patients undergoing percutaneous coronary intervention
Authors: Piccolo Raffaele , Biase Chiara De , D’Anna Carolina , Trimarco Bruno , Piscione Federico , Galasso Gennaro
Published: February 2015

Although bivalirudin has been shown to reduce bleeding events in patients undergoing percutaneous coronary intervention, residual concerns remain about a possible higher risk of early (within 30 days) stent thrombosis (ST). Therefore, we performed a meta-analysis of randomised trials reporting ST events with bivalirudin compared to other antithrombotic therapies (heparins ± glycoprotein IIb/IIIa inhibitors). A systematic literature search of electronic resources was performed through May, 2014. The primary endpoint was definite early ST, according to Academic Research Consortium criteria. Secondary endpoints included: all-cause death, myocardial infarction and major bleeding. A total of 11 trials, including 16,415 patients, were accrued. Compared to other regimens, bivalirudin significantly increased the risk of early ST (odds ratio [OR]=1.80; 95 % confidence interval [CI], 1.28 2.52; p=0.0007) and reduced the risk of major bleeding (OR [95 %CI]=0.64 [0.51 0.82], p=0.0003), with a comparable risk of mortality or myocardial infarction. The higher risk of early ST was mainly attributable to acute (OR [95 % CI] =4.33 [2.33 8.05], p < 0.001) than subacute (OR [95 % CI] =0.89 [0.53 1.50], p =0.67) ST events (p for interaction < 0.001). Non-fatal myocardial infarction was the most common presentation (83 %) of early ST events, while death occurred infrequently (about 5 %). In conclusion, in patients undergoing PCI, bivalirudin compared to heparins is associated with a higher risk of early ST, which is mainly related to more frequent acute events. Further studies are required to evaluate alternative strategies to mitigate this risk, without hampering the benefits derived from the reduction in bleeding events with bivalirudin.
Atrial Fibrosis and Conduction Slowing in the Left Atrial Appendage of Patients Undergoing Thoracoscopic Surgical Pulmonary Vein Isolation for Atrial Fibrillation
Authors: Krul Sébastien P.J. , Berger Wouter R. , Smit Nicoline W. , van Amersfoorth Shirley C.M. , Driessen Antoine H.G. , van Boven Wim Jan , Fiolet Jan W.T. , van Ginneken Antoni C.G. , van der Wal Allard C. , de Bakker Jacques M.T. , Coronel Ruben , de Groot Joris R.
Published: February 2015

Background—

Atrial fibrosis is an important component of the arrhythmogenic substrate in patients with atrial fibrillation (AF). We studied the effect of interstitial fibrosis on conduction velocity (CV) in the left atrial appendage of patients with AF.

Methods and Results—

Thirty-five left atrial appendages were obtained during AF surgery. Preparations were superfused and stimulated at 100 beats per minute. Activation was recorded with optical mapping. Longitudinal CV (CV
L
), transverse CV (CV
T
), and activation times (>2 mm distance) were measured. Interstitial collagen was quantified and graded qualitatively. The presence of fibroblasts and myofibroblasts was assessed immunohistochemically. Mean CV
L
was 0.55±0.22 m/s, mean CV
T
was 0.25±0.15 m/s, and the mean activation time was 9.31±5.45 ms. The amount of fibrosis was unrelated to CV or patient characteristics. CV
L
was higher in left atrial appendages with thick compared with thin interstitial collagen strands (0.77±0.22 versus 0.48±0.19 m/s;
P
=0.012), which were more frequently present in persistent patients with AF. CV
T
was not significantly different (
P
=0.47), but activation time was 14.93±4.12 versus 7.95±4.12 ms in patients with thick versus thin interstitial collagen strands, respectively (
P
=0.004). Fibroblasts were abundantly present and were associated with the presence of thick interstitial collagen strands (
P
=0.008). Myofibroblasts were not detected in the left atrial appendage.

Conclusions—

In patients with AF, thick interstitial collagen strands are associated with higher CV
L
and increased activation time. Our observations demonstrate that the severity and structure of local interstitial fibrosis is associated with atrial conduction abnormalities, presenting an arrhythmogenic substrate for atrial re-entry.
Myocardial Adaptations to Recreational Marathon Training Among Middle-Aged Men
Authors: Zilinski Jodi L. , Contursi Miranda E. , Isaacs Stephanie K. , Deluca James R. , Lewis Gregory D. , Weiner Rory B. , Hutter Adolph M. , d’Hemecourt Pierre A. , Troyanos Christopher , Dyer K. Sophia , Baggish Aaron L.
Published: February 2015

Background—

Myocardial adaptations to exercise have been well documented among competitive athletes. To what degree cardiac remodeling occurs among recreational exercisers is unknown. We sought to evaluate the effect of recreational marathon training on myocardial structure and function comprehensively.

Methods and Results—

Male runners (n=45; age, 48±7 years; 64% with ≥1 cardiovascular risk factor) participated in a structured marathon-training program. Echocardiography, cardiopulmonary exercise testing, and laboratory evaluation were performed pre and post training to quantify changes in myocardial structure and function, cardiorespiratory fitness, and traditional cardiac risk parameters. Completion of an 18-week running program (25±9 miles/wk) led to increased cardiorespiratory fitness (peak oxygen consumption, 44.6±5.2 versus 46.3±5.4 mL/kg per minute;
P
<0.001). In this setting, there was a significant structural cardiac remodeling characterized by dilation of the left ventricle (end-diastolic volume, 156±26 versus 172±28 mL,
P
<0.001), right ventricle (end-diastolic area=27.0±4.8 versus 28.6±4.3 cm
2
;
P
=0.02), and left atrium (end-diastolic volume, 65±19 versus 72±19;
P
=0.02). Functional adaptations included increases in both early (E′=12.4±2.5 versus 13.2±2.0 cm/s;
P
=0.007) and late (A′=11.5±1.9 versus 12.2±2.1 cm/s;
P
=0.02) left ventricular diastolic velocities. Myocardial remodeling was accompanied by beneficial changes in cardiovascular risk factors, including body mass index (27.0±2.7 versus 26.7±2.6 kg/m
2
;
P
<0.001), total cholesterol (199±33 versus 192±29 mg/dL;
P
=0.01), low-density lipoprotein (120±29 versus 114±26 mg/dL;
P
=0.01), and triglycerides (100±52 versus 85±36 mg/dL;
P
=0.02).

Conclusions—

Among middle-aged men, recreational marathon training is associated with biventricular dilation, enhanced left ventricular diastolic function, and favorable changes in nonmyocardial determinants of cardiovascular risk. Recreational marathon training may, therefore, serve as an effective strategy for decreasing incident cardiovascular disease.
Ideal Cardiovascular Health Predicts Functional Status Independently of Vascular Events: The Northern Manhattan Study
Authors: Dhamoon Mandip S. , Dong Chuanhui , Elkind Mitchell S. V. , Sacco Ralph L.
Published: February 2015

Background

We hypothesized that the American Heart Association's metric of ideal cardiovascular health (
CVH
) predicts improved long‐term functional status after adjusting for incident stroke and myocardial infarction.

Methods and Results

In the prospective, multiethnic Northern Manhattan Study, stroke‐free individuals in northern Manhattan aged ≥40 years had annual assessments of the primary outcome of functional status with the Barthel index (
BI
), for a median of 13 years. Ideal
CVH
was calculated as a composite of 7 measures, each scored on a scale of 0 to 2. Primary predictors were (1) number of ideal
CVH
metrics, and (2) total score of all
CVH
metrics. Of 3219 participants, mean age was 69 years (
SD
10), 63% were female, 21% were white, 25% were non‐Hispanic black, and 54% were Hispanic. Twenty percent had 0 to 1 ideal
CVH
metrics, 32% had 2, 30% had 3, 14% had 4, and 4% had 5 to 7. Both number of ideal
CVH
categories and higher
CVH
metric scores were associated with higher mean
BI
scores at 5 and 10 years. 0047 Gradients persisted when results were adjusted for incident stroke and myocardial infarction, when mobility and nonmobility domains of the
BI
were analyzed separately, and when
BI
was analyzed dichotomously. At 10 years, in a fully adjusted model, differences in mean
BI
score were lower for poor versus ideal physical activity (3.48 points,
P
<0.0001) and fasting glucose (4.58 points,
P
<0.0001).

Conclusions

Ideal
CVH
predicts functional status, even after accounting for incident vascular events. Vascular functional impairment is an important outcome that can be reduced by optimizing vascular health.
Impact of Duration of Mitral Regurgitation on Outcomes in Asymptomatic Patients With Myxomatous Mitral Valve Undergoing Exercise Stress Echocardiography
Authors: Naji Peyman , Asfahan Fadi , Barr Tyler , Rodriguez L. Leonardo , Grimm Richard A. , Agarwal Shikhar , Thomas James D. , Gillinov A. Marc , Mihaljevic Tomislav , Griffin Brian P. , Desai Milind Y.
Published: February 2015

Background

Significant mitral regurgitation (
MR
) typically occurs as holosystolic (
HS
) or mid‐late systolic (
MLS
), with differences in volumetric impact on the left ventricle (
LV
). We sought to assess outcomes of degenerative
MR
patients undergoing exercise echocardiography, separated based on
MR
duration (
MLS
versus
HS
).

Methods and Results

We included 609 consecutive patients with ≥
III
+myxomatous
MR
undergoing exercise echocardiography:
HS
(n=487) and
MLS
(n=122).
MLS MR
was defined as delayed appearance of
MR
signal during mid‐late systole on continuous‐wave Doppler while
HS MR
occurred throughout systole. Composite events of death and congestive heart failure were recorded. Compared to
MLS MR
,
HS MR
patients were older (60±14 versus 53±14 years), more were males (72% versus 53%), and had greater prevalence of atrial fibrillation (16% versus 7%; all
P
<0.01).
HS MR
patients had higher right ventricular systolic pressure (
RVSP
) at rest (33±11 versus 27±9 mm Hg), more flail leaflets (36% versus 6%), and a lower number of metabolic equivalents (
MET
s) achieved (9.5±3 versus 10.5±3), compared to the
MLS MR
group (all
P
<0.05). There were 54 events during 7.1±3 years of follow‐up. On step‐wise multivariable analysis,
HS
versus
MLS MR
(
HR
4.99 [1.21 to 20.14]), higher
LV
ejection fraction (hazard ratio [
HR
], 0.94 [0.89 to 0.98]), atrial fibrillation (
HR
, 2.59 [1.33 to 5.11]), higher
RVSP
(
HR
, 1.05 [1.03 to 1.09]), and higher percentage of age‐ and gender‐predicted
MET
s (
HR
, 0.98 [0.97 to 0.99]) were independently associated with adverse outcomes (all
P
<0.05).

Conclusion

In patients with ≥
III
+myxomatous
MR
undergoing exercise echocardiography, holosystolic
MR
is associated with adverse outcomes, independent of other predictors.
Neuroimaging Markers for Early Neurologic Deterioration in Single Small Subcortical Infarction
Authors: Jeong Han-Gil , Kim Beom Joon , Yang Mi Hwa , Han Moon-Ku , Bae Hee-Joon
Published: February 2015

Background and Purpose—

Early neurological deterioration (END) occurs in ≥20% of single small subcortical infarctions (SSSIs; axial diameter ≤20 mm in the perforator territories) and deters functional recovery. Both microvasculopathies and atherosclerosis have been proposed to independently contribute to the occurrence of END in SSSI cases. We hypothesized that the occurrence of END in SSSIs differs according to the pathological process.

Methods—

We collected data from 587 patients with SSSI within 48 hours of onset from a prospective stroke registry containing 4961 case records. Independent reviewers, blinded to END information, rated neuroimaging characteristics, including relevant artery stenosis (0% to 50% stenosis of the adjacent arteries on magnetic resonance angiography), branch atheromatous lesions (≥4 consecutive axial cuts or extensions from the basal surface of the pons), white matter hyperintensities, old lacunar infarctions, and cerebral microbleeds.

Results—

END occurred in 79 (13.5%) cases, including 6 recurrences, 68 progressions, 1 symptomatic hemorrhagic transformation, 1 others, and 3 unknowns. END increased the National Institutes of Health Stroke Scale score by 2.3±1.4 points. Patients with END showed higher frequencies of modified Rankin Scale scores of 3 to 6 after 3 months compared with patients without END (49% versus 23%). Patients with relevant artery stenosis (adjusted odds ratio, 1.91; 95% confidence interval, 1.13–3.21) and branch atheromatous lesions (adjusted odds ratio, 2.98; 95% confidence interval, 1.80–4.93) had significantly higher odds of exhibiting END. However, such an association was not detected with small vessel disease markers.

Conclusions—

Our analysis indicated a potential contribution of the localized atherosclerotic process to END in SSSIs. Precautionary measures might be used for SSSIs suggestive of atherosclerotic pathologies.
Significance of Intraventricular Hemorrhage in Acute Intracerebral Hemorrhage
Authors: Chan Edward , Anderson Craig S. , Wang Xia , Arima Hisatomi , Saxena Anubhav , Moullaali Tom J. , Heeley Emma , Delcourt Candice , Wu Guojun , Wang Jinchao , Chen Guofang , Lavados Pablo M. , Stapf Christian , Robinson Thompson , Chalmers John , Huang Yining
Published: February 2015

Background and Purpose—

Intraventricular hemorrhage (IVH) with spontaneous intracerebral hemorrhage indicates a poor prognosis but uncertainty exists over the pattern of association. We aimed to elucidate risk associations of IVH and outcome in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) data set.

Methods—

INTERACT2 was an international prospective, open-blinded end point, randomized controlled trial in 2839 patients with intracerebral hemorrhage (<6 hours) with elevated systolic blood pressure randomly assigned to intensive (target systolic blood pressure <140 mm Hg) or guideline-based (systolic blood pressure <180 mm Hg) blood pressure management. Associations of baseline IVH in 740 of 2613 (28%) patients and poor outcomes (death and major disability defined on the modified Rankin Scale) at 90 days were determined in linear and logistic regression models.

Results—

Patients with IVH were significantly older and with greater neurological impairment, history of ischemic stroke, and larger hematomas more often deep hemisphere located at presentation, after adjustment for other baseline variables. Death or major disability occurred in 66% with IVH versus 49% in intracerebral hemorrhage–alone patients (adjusted odds ratio, 1.68; 95% confidence interval, 1.38–2.06;
P
<0.01). Associations of IVH volume and clinical outcomes were strong and near continuous. Adjusted analyses by thirds of IVH volume indicate thresholds of ≈5 and 10 mL for significantly increased odds of death and death or major disability, respectively.

Conclusions—

A strong association exists between the amount of IVH and poor outcome in intracerebral hemorrhage. An IVH volume of 5 to 10 mL emerges as a significant threshold for decision making on prognosis in these patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00716079.
Redescriptions of Hypogastruridae and Onychiuridae (Collembola) described by David L. Wray
Authors: BERNARD ERNEST C.
Published: February 2015

Species of Hypogastruridae and Onychiuridae described by D. L. Wray were reexamined and redescribed where necessary from type material and other specimens. Mitchellania hermosa is redescribed and transferred to Ceratophysella. Hypogastrura ireneae is redescribed and H. gravesi is validated with additional material. Hypogastrura gami is synonymized with H. humi and H. utahensis is synonymized with H. promatro. A lectotype is designated for Schoettella (Knowltonella) idahoensis. Achorutes magnoliana is confirmed as a synonym of Schoettella glasgowi. Xenylla carolinensis is synonymized with Xenyllodes armatus Axelson (Odontellidae). Onychiurus mai is transferred to the genus Leeonychiurus and becomes L. mai, and O. magninus is transferred to Heteraphorura and becomes H. magnina. Additional details are given for Onychiurus wilchi.
A new species of Rhadinella (Serpentes: Colubridae) from the Pacific versant of Oaxaca, Mexico
Authors: CAMPBELL JONATHAN A.
Published: February 2015

I describe a new species of Rhadinella from the Pacific versant of Oaxaca, Mexico, a region where the genus was previously unknown. This diminutive snake is a member of a group of snakes that have dark dorsal coloration, which mostly or completely obfuscates a pattern of longitudinal striping characteristic of most species of Rhadinella. The closest relative of the new species, on the basis of morphological similarities, appears to be Rhadinella pilonaorum which occurs to the east of the Isthmus of Tehuantepec about 800 km from the type-locality of the new species.
A catalogue of the types of Stratiomyidae (Diptera: Brachycera) in the collection of the Museu de Zoologia da Universidade de São Paulo, Brazil
Authors: FACHIN DIEGO AGUILAR , LAMAS CARLOS JOSÉ EINICKER
Published: February 2015

Following a recommendation of the International Code of Zoological Nomenclature, a catalogue of the type specimens of Stratiomyidae (Diptera: Brachycera) held in the collection of the Museu de Zoologia da Universidade de São Paulo, Brazil (MZUSP) is provided, with information on 30 type specimens (including 14 primary types) of 17 Neotropical species.
A new Mexican species of Megarthrus Curtis (Coleoptera, Staphylinidae, Proteininae)
Authors: RODRÍGUEZ WILLIAM DAVID , NAVARRETE-HEREDIA JOSÉ LUIS
Published: February 2015

The genus Megarthrus Curtis with about 140 species described, is the largest of the subfamily Proteininae (Coleoptera: Staphylinidae) (Cuccodoro 2011; López-García et al. 2011). It is distributed worldwide (Cuccodoro 1999) and has an amphipolar distribution, being more diverse in Holarctic region (Newton 1985). In the tropics, the ecological requirements of Megarthrus species restrict their presence to mountain areas, showing high levels of endemism, making a taxon potentially informative for biogeographic analysis (Cuccodoro 1998). In Mexico there was only one described  species: Megarthrus altivagans Bernhauer, 1929, but it is known that there are several undescribed species (Navarrete-Heredia et al. 2002). Cuccodoro (2011),  recognised “eleven species  from Mexico, eleven species from Costa Rica, Guatemala, Honduras, Nicaragua and Panama, and fifteen species from Bolivia, southern Brazil, Colombia, Ecuador, Peru and Venezuela”. In this paper we describe a new species of Mexican Megarthrus from the State of Jalisco.
Changes of Early Summer Precipitation in the Korean Peninsula and Nearby Regions Based on RCP Simulations
Authors: Hong Ja-Young , Ahn Joong-Bae
Published: February 2015

In this study, the projected regional precipitation changes over northeast Asia (NEA) during early summer [May–July (MJJ)] for the late twenty-first century (2071–2100) were investigated using a high-resolution regional climate model (WRF3.4) based on the representative concentration pathways (RCPs) induced by the global circulation model (HadGEM2-AO). The increased horizontal resolution of the regional model with a 12.5-km horizontal resolution enabled it to reproduce the terrain-following features reasonably well compared to low-resolution reanalysis and HadGEM2-AO model data. The results of a regionally downscaled historical (1981–2010) experiment (D_Historical) demonstrated the model’s ability to capture the spatial and temporal variations of rainband migrating meridionally during MJJ over NEA. According to the regional model projection, intensive precipitation will increase and the rainband will affect the Korean Peninsula approximately 10 days earlier than in the D_Historical cases in both RCP4.5 and RCP8.5 (2071–2100). The precipitation will also increase in most of the domain, particularly in the southern Korean Peninsula and Kyushu, Japan. These increases in precipitation are attributed to increases in the northward moist transport coming from the lower latitudes and moist static instability in the lower atmosphere. According to this study, the convective precipitation contributes mainly to the increase in total precipitation. On the other hand, the large-scale nonconvective precipitation related to the stationary front will not change significantly but even tends to decrease approximately from the middle of July. The extreme precipitation intensity is also projected to increase by at least 22% (38%) in RCP4.5 (RCP8.5).
L’(in)efficacia dell’amore in Non ti muovere di Margaret Mazzantini
Authors: Alfano Barbara
Published: February 2015

Questo saggio si occupa del significato dell’amore passionale nel romanzo di Margaret Mazzantini Non ti muovere (2001). Narratore e protagonista della storia è Timoteo, chirurgo di successo, sposato con Elsa, la cui figlia adolescente, Angela, si trova in ospedale tra la vita e la morte. Ad Angela, che non può ascoltarlo, Timo racconta la storia della relazione extraconiugale che ebbe nel periodo della nascita della ragazza e che cambiò il suo modo di guardare all’umanità. Quella storia iniziò con uno stupro.

Nel romanzo, l’amore è rappresentato come forza rivoluzionaria che diventa strumento critico di conoscenza dell’altro e agisce spingendo il protagonista fuori dalla sua vita altoborghese, costringendolo a ripensare la sua umanità. Timoteo si apre così a una comprensione del genere umano più profonda, laddove norme e pratiche sociali della sua classe d’appartenenza avevano invece fallito. Eppure, a dispetto del potere che esercita sull’individuo, l’amore lascia inalterate le strutture sociali che sfida e si propone di cambiare. In questa prospettiva, lo stupro resta un elemento non poco problematico della lettura critica del testo.
African psychology and the Africentric paradigm to clinical diagnosis and treatment
Authors: Nwoye Augustine
Published: February 2015

The notion of clinical or psychological diagnosis in African psychology is used, at times, to refer to the redressive action that is taken to determine the source of a difficult/abnormal illness. The need for such an interventive action arises in the face of a sudden or ‘strange’ illness that befalls a family member and refuses to abate after all medicines (including Western psychiatric hospitalization) have been administered. Under such a situation, the tendency within the Africentric paradigm to mental health and illness is to see such a challenging illness as an extraordinary or abnormal illness that carries a hidden message that must first be decoded before a decisive solution to achieving a cure can be found. Consequently, recognizing certain illnesses as ‘symbolic illnesses’ or ones with a hidden meaning, indigenous African peoples routinely persuade themselves that they must go beyond the ‘information given’ (Bruner, 1986) to determine ‘who’ is speaking through such an illness and what they are expected to do to effect a cure. In this way, they try to set their eyes not only on what is happening to the sick one (the observable manifestations of the illness) but also on the question of identifying the agent behind its onset and escalation in their approach for questioning the misfortune. This article draws attention to the missing link in the Western paradigm to psychopathology and treatment that makes it unable to deal decisively with certain illness presentations of the Black African client.
Sibling Gender Configuration and Family Processes
Authors: van der Pol Lotte D. , Mesman Judi , Groeneveld Marleen G. , Endendijk Joyce J. , van Berkel Sheila R. , Hallers-Haalboom Elizabeth T. , Bakermans-Kranenburg Marian J.
Published: February 2015

The current study focuses on the effects of sibling gender configuration on family processes during early childhood. In a sample of 369 two-parent families with two children (youngest 12 months, oldest about 2 years older), both siblings’ noncompliant and oppositional behaviors and fathers’ and mothers’ sensitivity and discipline strategies were observed. Both siblings’ aggressive behaviors and empathy of the oldest sibling were assessed with parent-reports. Children in families with two sons showed more problematic interaction patterns compared with children in families with an oldest girl. In families with two boys, older siblings were more aggressive and fathers were less sensitive toward their youngest child in comparison with families with two girls. Furthermore, in boy–boy families older siblings showed more oppositional behavior and younger siblings more noncompliance compared with girl–boy families. These findings highlight the importance of sibling gender configuration in the development of child behavior and parent–child interactions.