bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract C52: Gene silencing of c-met leads to brain metastasis inhibitory effects
Authors: Lee Se Jeong , Lee Hye Won , Song Mi Young , Lee Kee Hang , Lee Young-Eun , Joo Kyeung Min
Published: August 2014

An unfortunate consequence of improvements in the treatments of advanced primary cancers is the concurrent increase of metastatic brain tumors. Despite of unfavorable clinical prognosis, radiation therapy is still the only viable treatment option for brain metastases. Expression of c-Met induces cell migration and invasion in many cancers, which are indispensable steps for metastasis. Accordingly, we examined the effects of gene silencing of c-Met on brain metastasis to evaluate the possibility of c-Met as a potential target. MDA-MB-435 cells were transfected with c-Met targeting short hairpin RNAs (shRNAs). Effects of c-Met shRNAs on the expression of epithelial mesenchymal transition (EMT) related proteins, in vitro migration, and in vivo brain metastasis were examined. Expression of mesenchymal markers and in vitro migration of MDA-MB-435 cells were significantly inhibited by introduction of c-Met shRNAs. When c-Met-silenced MDA-MB-435 cells were stereotactically implanted into the brains of immune-compromised mice or injected into the right internal carotid arteries, c-Met-silenced MDA-MB-435 cells produced significantly smaller tumor masses or survival time was significantly prolonged, respectively, compared with MDA-MB-435 cells transfected with control shRNA. The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease.

Citation Format: Se Jeong Lee, Hye Won Lee, Mi Young Song, Kee Hang Lee, Young-Eun Lee, Kyeung Min Joo. Gene silencing of c-met leads to brain metastasis inhibitory effects. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C52.
Abstract C87: Regulation of stemness by Hippo-YAP pathway under hypoxia in hepatocellular carcinoma
Authors: Kim Ji Su , Ahn Ei Yong , Park Young Nyun
Published: August 2014

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer-related death. The Hippo-YAP signaling pathway is gaining recognition as it plays an important role in both organ size control and tumorigenesis. Liver-specific ablation of WW45 in rodent models (one of the tumor suppressive Hippo pathway components in mammals) has been reported to increase liver size and expand hepatic stem/progenitor cells (oval cells) and to develop HCC eventually. The expression of YAP also has been reported as an independent poor prognostic marker for human HCCs. Amphiregulin is a downstream target of YAP and is a member of the EGF family, which is implicated in cancer stem cells in HCC. Cancer stem cells have the ability to self-renew, differentiate, and proliferate, and have greater tumorigenicity, chemoresistance, and resistance to hypoxia. HCCs expressing stem cell makers have actually been reported to be associated with poor prognosis and aggressive biological behavior. The aim of this study is to investigate the Hippo-YAP pathway and its related oncogenic signaling in HCCs expressing stem cell markers. The effect of amphiregulin on the regulation of the Hippo-YAP pathway was also studied to identify potential molecular therapeutic targets for HCCs expressing stem cell markers. Under hypoxic condition, the expression of cancer stem cell markers (EpCAM, CD133, and CK19) was upregulated in a time dependent manner and the Hippo-YAP pathway was oncogenically activated in four HCC cell lines (HepG2, Hep3B, Huh7, and SK-Hep1). In addition, the treatment of recombinant human amphiregulin dephosphorylated and activated YAP pathway. Therefore, up-regulation of cancer stem cell markers with activation of oncogenic YAP pathway in HCC cell lines might suggest the acquisition of survival advantage of tumor cells under hypoxia. The relationship between the regulatory mechanism of cancer stem cells and the Hippo-YAP pathway can be used for molecular target of chemotherapy for HCC.

Citation Format: Ji Su Kim, Ei Yong Ahn, Young Nyun Park. Regulation of stemness by Hippo-YAP pathway under hypoxia in hepatocellular carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C87.
Abstract IA14: Inhibition of Ron kinase blocks conversion of micrometastases to overt metastases by boosting antitumor immunity
Authors: Welm Alana
Published: August 2014

Many “non-metastatic” cancers have spawned clinically undetectable metastatic colonies even prior to diagnosis. Eventual outgrowth of these microscopic lesions is the cause of metastatic relapse and death from cancer, yet the events that dictate when and how disseminated cancer cells convert to overt metastasis are largely unknown. We utilized mouse genetics and tissue complementation strategies in a murine model of spontaneous metastasis to interrogate the role of macrophage stimulating protein (MSP) and its receptor, Ron, in metastasis. Our data reveal the MSP/Ron pathway as a key mediator in conversion of micrometastases to bona fide metastatic lesions through immune suppression. Genetic deletion of Ron tyrosine kinase activity specifically in the host profoundly blocked metastasis. Our data show that loss of Ron function promotes an effective anti-tumor CD8+ T cell response, which specifically inhibits outgrowth of seeded metastatic colonies. Treatment of mice with a Ron-selective kinase inhibitor prevented outgrowth of lung metastasis, even when administered after micrometastatic colonies had already been established. Our findings indicate that Ron inhibitors may hold potential to specifically prevent outgrowth of micrometastases in cancer patients in the adjuvant setting.

Citation Format: Alana Welm. Inhibition of Ron kinase blocks conversion of micrometastases to overt metastases by boosting antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA14.
Abstract IA15: HIFs, hypoxia, and tumor progression
Authors: Simon M. Celeste
Published: August 2014

Intratumoral hypoxia and expression of Hypoxia Inducible Factor 1α (HIF1α) correlate with metastasis and poor survival in sarcoma patients. We demonstrate here that hypoxia controls sarcoma cell metastasis through a novel mechanism in which HIF1α induces the expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). PLOD2 hydroxylates procollagen, consequently altering the structure of extracellular collagen fibers along which transformed cells migrate in primary tumors. We show that loss of HIF1α or PLOD2 expression disrupts collagen deposition, cell migration and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSL-KrasG12D/+; Trp53fl/fl murine sarcoma models. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF1α-deficient cells and tumors, and microarray analyses of human sarcomas reveal elevated HIF1α and PLOD2 expression in metastatic primary lesions. Collectively, these data indicate that whereas HIF1α activity modifies pre-metastatic niches in carcinomas, it controls sarcoma metastasis through PLOD2-dependent collagen deposition in primary tumors. Therefore, we conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination.

Citation Format: M. Celeste Simon. HIFs, hypoxia, and tumor progression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA15.
Abstract IA19: Understanding the dynamics of cancer: From developmental pathways to in vivo imaging
Authors: Reya Tannishtha
Published: August 2014

Our research focuses on the signals that control hematopoietic stem cell self-renewal and differentiation, how these signals are utilized during regeneration and how their dysregulation may lead to cancer. Using a multitude of genetic models, we have shown that classic developmental signaling pathways such as Wnt, Hedgehog and Notch play key roles in stem cell growth and regeneration and are dysregulated during leukemia development. In addition, we have used real-time imaging strategies to show that hematopoietic stem cells have the capacity to undergo both symmetric and asymmetric division, and that shifts in the balance between these modes of division are controlled by the microenvironment and subverted by oncogenes. Importantly, we have shown that regulators of this process, including the cell fate determinant Musashi, can promote aggressive cancers and could serve as critical targets for diagnostics and therapy. Most recently, we have developed a high resolution in vivo imaging system that has allowed us to begin to map the behavior and interactions of hematopoietic stem cells with the microenvironment within living animals, and to define how these change during regeneration and cancer formation.

Citation Format: Tannishtha Reya. Understanding the dynamics of cancer: From developmental pathways to in vivo imaging. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA19.
Thrombospondin-1 Is Produced by Retinal Glial Cells and Inhibits the Growth of Vascular Endothelial Cells
Authors: Yafai Yousef , Eichler Wolfram , Iandiev Ianors , Unterlauft Jan-Darius , Jochmann Claudia , Wiedemann Peter , Bringmann Andreas
Published: August 2014

Background/Aims: By the release of antiangiogenic factors, Müller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Müller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis. Methods: Secretion of TSP-1 by cultured Müller cells was determined with ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells (BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration assays, and Western blotting, respectively. Results: Cultured Müller cells secrete TSP-1 under normoxic and hypoxic (0.2% O2) conditions. Secretion of TSP-1 was increased in hypoxia compared to normoxia. In rat retinal slices, glial, retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal glial cells in preretinal membranes from human subjects with nonhypoxic epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy, respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF-induced proliferation and migration of BRECs and decreased the phosphorylation level of ERK1/2 in BRECs. Conclusion: The data suggest that Müller cells are one major source of TSP-1 in the normal and ischemic retina. Glia-derived TSP1 may inhibit angiogenic responses in the ischemic retina.
Gender Difference in Arterial Stiffness in a Multicenter Cross-Sectional Study: The Korean Arterial Aging Study (KAAS)
Authors: Kim Jang-Young , Park Jeong Bae , Kim Dong Soo , Kim Kee Sik , Jeong Jin Won , Park Jong Chun , Oh Byung Hee , Chung Namsik ,   on behalf of the KAAS investigators
Published: August 2014

Elevated arterial stiffness has emerged as an important risk factor for future cardiovascular (CV) events in men and women. However, gender-related differences in arterial stiffness have not been clearly demonstrated. We thus determine whether gender affects arterial stiffness in subjects with and without CV risk factors. We consecutively enrolled 1,588 subjects aged 17-87 years (mean age: 46.5; 51% women) from the Korean Arterial Aging Study (KAAS), which is a multicenter registry from 13 university hospitals in Korea for the evaluation of arterial stiffness. We compared markers of arterial stiffness - central augmentation index (AIx), aortic pulse wave velocity (PWV), and pulse pressure (PP) amplification - in apparently healthy men and women without risk factors with those in high-risk subjects with a smoking habit, hypertension, diabetes, and dyslipidemia but without drug treatment. Aortic PWV and PP amplification were significantly higher in men than in women (7.78 ± 1.16 vs. 7.64 ± 1.15 m/s, p = 0.015, and 1.39 ± 0.22 vs. 1.30 ± 0.18, p < 0.001, respectively). However, women had a significantly higher central AIx than men (23.5 ± 11.9 vs. 16.1 ± 12.6%, p < 0.001). The central AIx and aortic PWV values were significantly higher in the high-risk group than in the healthy group for both men and women. In men, central AIx and aortic PWV were associated positively with age and blood pressure, and negatively with body mass index. In women, central AIx was positively related to age, diastolic blood pressure, and serum cholesterol levels. Aortic PWV was positively related to age, systolic blood pressure, fasting glucose, and heart rate. PP amplification was associated negatively with age and blood pressure and positively with heart rate in both men and women. In conclusion, arterial stiffness is mainly determined by sex, age, and blood pressure. Markers of arterial stiffness differ between men and women. Dyslipidemia and glucose contribute to a modest increase in arterial stiffness only in women. Therefore, the arteries of women may be more vulnerable to CV risk factors than those of men. © 2014 S. Karger AG, Basel
Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury
Authors: Kapopara Piyushkumar , Felden Johann von , Soehnlein Oliver , Wang Yong , Napp L. Christian , Sonnenschein Kristina , Wollert Kai , Schieffer Bernhard , Gaestel Matthias , Bauersachs Johann , Bavendiek Udo
Published: August 2014

Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and reendothelialisation. Therefore, we investigated the role of MK2 in remodelling and reendothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-densitylipoprotein- receptor-deficient mice (ldlr-/- ) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr-/-/mk2-/- ) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved reendothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty.
Prostaglandin E2 levels and platelet function are different in cord blood compared to adults
Authors: Haidl Harald , Leschnik Bettina , Leis Hans-Joerg , Heinemann Akos , Muntean Wolfgang , Schlagenhauf Axel
Published: August 2014

Neonatal platelets support primary haemostasis and thrombin generation as well as adult platelets, despite observable hypoaggregability in vitro. High prostaglandin E2 levels at accouchement could account for inhibited platelet function via the EP4 receptor. We set out to determine prostaglandin E2 plasma levels in cord blood of healthy neonates and evaluate the impact of prostaglandin E2 on platelet function in adult and cord blood samples. Prostaglandin E2 plasma levels were measured in cord blood and venous adult blood using GC-MS. Impact of prostaglandin E2 on platelet aggregation was measured by spiking cord blood and adult samples. Contributions of EP3 and EP4 receptors were evaluated using respective antagonists. Intracellular cAMP concentrations were measured using a commercial ELISA-kit. Prosta-glandin E2 plasma levels were substantially higher in cord blood than in adult samples. Spiking with prostaglandin E2 resulted in a slight but consistent reduction of platelet aggregation in adult blood, but response to PGE2 was blunted in cord blood samples. Aggregation response of spiked adult samples was still higher than with non-spiked cord blood samples. Blockage of EP4 receptors resulted in improved platelet aggregation in adult platelets upon prostaglandin E2 spiking, while aggregation in cord blood samples remained unaltered. Intracellular cAMP concentrations after preincubation with prostaglandin E2 were only increased in adult samples. In conclusion, very high prosta -glandin E2 concentrations in cord blood affect platelet function. This effect may partially explain neonatal platelet hypoaggregability. Peak levels of prostaglandin E2 can potentially protect against birth stressinduced platelet activation.
Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients
Authors: Schaefer Jordan , McBane Robert , Black David , Williams Lindsy , Moder Kevin , Wysokinski Waldemar
Published: August 2014

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.
Plasma Phospholipid Fatty Acid Biomarkers of Dietary Fat Quality and Endogenous Metabolism Predict Coronary Heart Disease Risk: A Nested Case‐Control Study Within the Women's Health Initiative Observational Study
Authors: Matthan Nirupa R. , Ooi Esther M. , Van Horn Linda , Neuhouser Marian L. , Woodman Richard , Lichtenstein Alice H.
Published: August 2014

Background

Although the relationship between dietary fat quality and coronary heart disease (
CHD
) risk has been evaluated, typically using diet questionnaires, results are inconsistent and data in postmenopausal women are limited. Plasma phospholipid fatty acid (
PL
‐
FA
) profiles, reflecting dietary intake and endogenous
FA
metabolism, may better predict diet–
CHD
risk.

Methods and Results

Using a nested case‐control design, we assessed the association between plasma
PL
‐
FA
profiles and
CHD
risk in 2448 postmenopausal women (1224 cases with confirmed
CHD
and 1224 controls matched for age, enrollment date, race/ethnicity, and absence of
CHD
at baseline and after 4.5 years of follow‐up) participating in the Women's Health Initiative observational study.
PL
‐
FA
profile was measured using gas chromatography. Product/precursor ratios were used to estimate stearoyl‐CoA‐desaturase (16:1n‐7/16:0, 18:1n‐9/18:0), Δ6‐desaturase (20:3n‐6/18:2n‐6), and Δ5‐desaturase (20:4n‐6/20:3n‐6) activities, indicators of endogenous
FA
metabolism. Multivariate conditional logistic regression was used to obtain odds ratios (95% CIs) for
CHD
risk. While no associations were observed for the predominant
PL
fatty acid (16:0, 18:0, 18:1n‐9, and 18:2n‐6), plasma
PL
–saturated fatty acid (1.20 [1.08 to 1.32]) and endogenously synthesized
PL
ω6 fatty acids (20:3n‐6; 3.22 [1.95 to 5.32]), 22:5n‐6; 1.63 [1.20 to 2.23]) and Δ6‐desaturase (1.25 [1.11 to 1.41]) were positively associated with
CHD
risk.
PL
‐ω3 fatty acids (20:5n‐3; 0.73 [0.58 to 0.93], 22:5n‐3; 0.56 [0.33 to 0.94], 22:6n‐3; 0.56 [0.39 to 0.80]), 18:1n‐7 (0.54 [0.29 to 0.99]), and Δ5‐desaturase (0.78 [0.70 to 0.88]) were inversely associated with
CHD
risk. Results support current guidelines regarding regular fish consumption. Additional findings include associations between endogenously synthesized fatty acids and
CHD
risk, which were partly explained by changes in Δ6‐desaturase and Δ5‐desaturase indexes, suggesting that in vivo metabolism may also play an important role in predicting
CHD
risk in this cohort of postmenopausal women.

Clinical Trial Registration

URL:
http://ClinicalTrials.gov
, Unique identifier: NCT01864122.
Choosing Wisely for Syncope: Low‐Value Carotid Ultrasound Use
Authors: Scott John W. , Schwartz Aaron L. , Gates Jonathan D. , Gerhard‐Herman Marie , Havens Joaquim M.
Published: August 2014

Background

The United States spends more than $750 billion annually on tests and procedures that do not benefit patients. Although there is no physiological indication for carotid ultrasound in “simple” syncope in the absence of focal neurological signs or symptoms suggestive of stroke, there is concern that this practice remains common for routine syncope workups.

Methods and Results

We used a 5% random‐sample Medicare claims database to evaluate large‐scale national trends in utilization of low‐value carotid ultrasound imaging for simple syncope. We found that 16.5% of all Medicare beneficiaries with simple syncope underwent carotid imaging and 6.5% of all carotid ultrasounds ordered in 2009 were for this low‐value indication. These findings were complemented by a manual chart review of 313 patients at a large academic medical center who underwent carotid ultrasound for simple syncope over a 5‐year period. For the 48 (15.4%) of 313 patients with stenosis ≥50%, carotid ultrasound did not yield a causal diagnosis. Only 2% of the 313 patients imaged experienced a change in medications after a positive study, and <1% of patients underwent a carotid revascularization procedure.

Conclusions

These data suggest that carotid ultrasound for patients with uncomplicated syncope are still commonly ordered and may be an easy target for institutions striving to curtail low‐value care.
Performing Public Spaces, Staging Collective Memory: 50 Kilometres of Files by Rimini Protokoll
Authors: Hahn Daniela
Published: August 2014

Since the 1960s, walking through urban spaces as an explorative artistic practice has become a manifestation of the blurring boundaries between theatre and what is called “public space.” Rimini Protokoll’s 50 Kilometres of Files turns an urban environment into a sonic space in which the city’s past and present converge, resonating with each walker’s step.
American Arms Manufacturing and the Onset of the War of 1812
Authors: Fagal Andrew J. B.
Published: August 2014

In 1803, President Thomas Jefferson appointed Tench Coxe Purveyor of Public Supplies. Using the considerable patronage at his disposal, Coxe aggressively promoted private military manufacturers, thus arguably now giving the U.S. the ability-when it had already long had ample reason-to declare war against England in 1812.
The Performance of Peace: Indians, Speculators, and the Politics of Property on the Maine Frontier, 1735–1737
Authors: Saxine Ian
Published: August 2014

In 1736, Penobscot and Massachusetts leaders cooperated to evict colonists from Native lands in Maine, rejecting the claims of a wealthy, powerful land speculator to that territory. This article finds that Native and European conceptions of landownership facilitated this unlikely alliance on what was an otherwise volatile frontier.
Fleecing Connecticut: David Humphreys and the Poetics of Sheep Farming
Authors: Sturges Mark
Published: August 2014

At the turn of the nineteenth century, the importation of a Spanish breed of merino sheep to the United States led to a dramatic period of agricultural intensification. Profiling David Humphreys, who promoted merino sheep in poetry and prose, this essay interprets the merino boom as a lesson in the dangers of rhetorical and environmental manipulation.
Communicating Across Communities
Authors: Calma Clarinda E.
Published: August 2014

In the sixteenth century, the Polish-Lithuanian Commonwealth was a multicultural and multidenominational country, where religious freedom was guaranteed by the General Warsaw Confederation Act of 1573. This climate of religious tolerance allowed a culture of public theological dispute to flourish within the realm. Printed in Vilnius in 1584, Gaspar Wilkowski’s Dziesięc mocnych dowodów [Ten Strong Reasons]—a translation of Edmund Campion’s Rationes decem—captured this culture of controversy and polemical dispute. To understand the significance of Wilkowski’s book this essay will situate it in its wider historical context of cross-confessional debates between Catholics and the Polish Brethren. Three other books will be discussed to demonstrate that Wilkowski’s translation was clearly written as an instrument of polemical dispute. A textual analysis of the work shows a change of emphasis from Campion’s book, consequently affecting the reader’s reception of the translated work. Understanding how the translator, in this case Wilkowski, made conscious changes in the original text to accommodate the particular needs of his target readership helps explain the purpose and structure of the Polish translation. In short, Wilkowski wanted to make his translation as relevant to his readers as possible.
“Paths Coincident”
Authors: Kilroy Gerard
Published: August 2014

Edmund Campion arrived in Dublin on August 25, 1570, on a travelling fellowship from St. John’s College, Oxford. This five-year leave of absence enabled him to postpone ordination in the Elizabethan church. Campion was invited to stay with the Recorder of Dublin, James Stanihurst, whose library was to satisfy his academic needs, and who was hoping that Campion might help with the university that formed a key part of the program of reform in Ireland. Campion had ignored calls from friends already at the English college in Douai to join them. Dublin was meant to be a quiet pause, allowing Campion to stay quietly within the establishment. It was not to be like that. This article argues that Ireland was the beginning and, thanks to the disastrous invasion in July 1579 by Nicholas Sander, the end of Campion’s troubles; that the rebellion stirred by Sander in Munster created such fear of an invasion in England that the Jesuit missionaries were doomed from the moment they landed at Dover one year later; that the radical arguments in favor of papal power to depose monarchs expressed in De visibili monarchia (1571), not the theological arguments for the Catholic and apostolic church in Rationes decem (1581), were at the center of Campion’s interrogations on the rack; and that the parallel lives of Campion and Sander reveal two completely contrasting views of the papacy, and of Rome.
A taxonomic mystery for more than 150 years: Identity, systematic position and Malagasy origin of the snake Elapotinus picteti Jan, 1862, and synonymy of Exallodontophis Cadle, 1999 (Serpentes: Lamprophiidae)
Authors: Kucharzewski Christoph , RASELIMANANA ACHILLE P. , Wang Cynthia , Glaw Frank
Published: August 2014

Elapotinus picteti Jan, 1862 is an enigmatic snake taxon that has been described without locality data. Genus and species, both based on the unique holotype, were considered to belong to the venomous African Aparallactinae for more than a century, but although this taxon was never rediscovered it was accepted as a valid species until present. To clarify the taxonomic status of E. picteti its characters were compared with literature and determination keys for the whole world. This literature survey and the subsequent study of type specimens revealed that the monotypic Elapotinus is a subjective senior synonym of the monotypic Malagasy pseudoxyrhophiine snake genus Exallodontophis Cadle, 1999 which is characterized by its unique aglyphous dentition. We therefore transfer Elapotinus from the lamprophiid subfamily Aparallactinae to the subfamily Pseudoxyrhophiinae. Furthermore, Elapotinus picteti strongly resembles the Malagasy species Exallodontophis albignaci (Domergue, 1984) in external morphology, coloration and dentition. As a consequence we consider Elapotinus picteti a subjective senior synonym of Exallodontophis albignaci.
Predictions of Climate Several Years Ahead Using an Improved Decadal Prediction System
Authors: Knight Jeff R. , Andrews Martin B. , Smith Doug M. , Arribas Alberto , Colman Andrew W. , Dunstone Nick J. , Eade Rosie , Hermanson Leon , MacLachlan Craig , Peterson K. Andrew , Scaife Adam A. , Williams Andrew
Published: August 2014

Decadal climate predictions are now established as a source of information on future climate alongside longer-term climate projections. This information has the potential to provide key evidence for decisions on climate change adaptation, especially at regional scales. Its importance implies that following the creation of an initial generation of decadal prediction systems, a process of continual development is needed to produce successive versions with better predictive skill. Here, a new version of the Met Office Hadley Centre Decadal Prediction System (DePreSys 2) is introduced, which builds upon the success of the original DePreSys. DePreSys 2 benefits from inclusion of a newer and more realistic climate model, the Hadley Centre Global Environmental Model version 3 (HadGEM3), but shares a very similar approach to initialization with its predecessor. By performing a large suite of reforecasts, it is shown that DePreSys 2 offers improved skill in predicting climate several years ahead. Differences in skill between the two systems are likely due to a multitude of differences between the underlying climate models, but it is demonstrated herein that improved simulation of tropical Pacific variability is a key source of the improved skill in DePreSys 2. While DePreSys 2 is clearly more skilful than DePreSys in a global sense, it is shown that decreases in skill in some high-latitude regions are related to errors in representing long-term trends. Detrending the results focuses on the prediction of decadal time-scale variability, and shows that the improvement in skill in DePreSys 2 is even more marked.
PISTE: A Snow-Physics Model Incorporating Human Factors for Groomed Ski Slopes*
Authors: Howard Rosie , Stull Roland
Published: August 2014

Accurately calculating snow-surface temperature and liquid water content for a groomed ski run, known as a ski piste, is crucial to the preparation of fast skis for alpine racing. Ski technicians can use forecasts of these variables to reduce ski–snow friction by applying layers of wax ahead of time. A new one-dimensional numerical Lagrangian snowpack model, Prognostic Implementation for Snow Temperature Estimation (PISTE), is presented that solves the heat-, liquid water–, and ice-budget equations to calculate these snow variables. In addition, the human effects of skiing and grooming are modeled. Meteorological measurements from a 5-day, clear-sky case study at a ski piste on Whistler Mountain, British Columbia, Canada, are prescribed to PISTE as boundary conditions. Because of a lack of interior snowpack measurements, PISTE was spun up from a dry, isothermal snowpack using repeated boundary conditions from 1 day of measurements. Initial conditions for the main model run that used the subsequent 4 days were taken from this spinup. Simulated and measured snow-surface temperatures show very good agreement, with slight cold daytime and warm nighttime biases (averaging 0.5° and 1°C, respectively). The modeled behavior of snowpack temperature and liquid water content profiles is consistent with previous literature having similar radiative boundary conditions. The case study indicates that PISTE is useful under simple conditions. It shows the potential to be developed into a more sophisticated model that can incorporate complex boundary conditions such as cloudiness and precipitation and can be driven by numerical weather prediction output.
Facial Palsy in Melkersson-Rosenthal Syndrome and Bell’s Palsy
Authors: Sun Baochun , Zhou Chengyong , Han Zeli
Published: August 2014

Objective:

The aim of this study was to compare genetic predilection and recurrence tendency between facial palsy in Melkersson-Rosenthal syndrome (MRS) and Bell’s palsy

Methods:

We carried out an investigation on patients with facial palsy in MRS and those with Bell’s palsy who visited the outpatient department in our hospital between February 2009 and February 2013. They were asked about familial history and whether it was the first episode, with the results recorded and compared.

Results:

There were 16 patients with facial palsy in MRS and 860 patients with Bell’s palsy involved in the study. Familial history was positive in 5 of 16 patients (31.3%) with facial palsy in MRS and 56 of 860 patients (6.5%) with Bell’s palsy ( P < .01). Twelve of 16 cases (75%) with facial palsy in MRS and 88 of 860 cases (10.2%) with Bell’s palsy had a history of facial palsy in the past ( P < .01).

Conclusion:

Compared to Bell’s palsy, facial palsy in MRS has an obvious genetic predilection and recurrence tendency.
Xenograft Model for Therapeutic Drug Testing in Recurrent Respiratory Papillomatosis
Authors: Ahn Julie , Bishop Justin A. , Akpeng Belinda , Pai Sara I. , Best Simon R.A.
Published: August 2014

Objective:

Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options.

Methods:

A biopsy of fresh tracheal papilloma was xenografted into a NOD- scid-IL2Rgammanull (NSG) mouse.

Results:

The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control.

Conclusion:

We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis.
DSM-IV and DSM-5 social anxiety disorder in the Australian community
Authors: Crome Erica , Grove Rachel , Baillie Andrew J , Sunderland Matthew , Teesson Maree , Slade Tim
Published: August 2014

Objective:

Current and accurate estimates of prevalence, correlates, comorbid concerns and treatment-seeking behaviours associated with disorders are essential for informing policy, clinical practice and research. The most recent snapshot of social anxiety disorder in Australia was published more than a decade ago, with significant changes to the accessibility of mental health treatment services and diagnostic measures occurring during this period. This paper aims to (i) update the understanding of social anxiety disorder, its associations and patterns of treatment-seeking behaviours in the Australian population, and (ii) explore the impact of revised diagnostic criteria detailed in the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) on prevalence estimates.

Methods:

The National Survey of Mental Health and Wellbeing (NSMHWB) was conducted by the Australian Bureau of Statistics in 2007, collecting information from a nationally representative random sample of 8841 Australians aged 16–85 years. The presence of social anxiety disorder diagnostic criteria and related disorders were assessed over 12 months and lifetime periods using the World Mental Health Composite International Diagnostic Interview.

Results:

Profiles of social anxiety disorder were consistent with previous estimates, with higher prevalence in females and younger age groups. Of the 8.4% of Australians meeting criteria for social anxiety disorder at some point in their lifetime (12-month prevalence 4.2%), a majority also experienced comorbid mental health concerns (70%). The revised performance-only specifier included in the DSM-5 was applicable to only 0.3% of lifetime cases. Just over 20% of people reporting social anxiety disorder as their primary concern sought treatment, most commonly through general practitioners.

Conclusions:

Social anxiety disorder continues to be prevalent in the Australian population and highly related to other disorders, yet few people experiencing social anxiety disorder seek treatment
The Role of Research Strategies and Professional Networks in Management Scholars’ Productivity
Authors: Seibert Scott E. , Kacmar K. Michele , Kraimer Maria L. , Downes Patrick E. , Noble David
Published: August 2014

We propose a model of knowledge creation, transfer, and adoption based on theories of creativity and social networks. We test our hypotheses using a sample of 119 full professors in management departments at U.S. universities. We examine the effects that two research strategies, coauthoring and working in multiple research fields, have on the number of publications in each of three journal quality tiers during an 8-year period. In addition, we examined the influence that having strong ties and a dense network of professional colleagues each has on the total number of citations garnered by those publications. Results showed a heterogeneous pattern of coauthoring (distributing coauthoring activity evenly across a greater number of coauthors) is positively related to the number of publications in the highest-quality journals for the focal researcher. The heterogeneity of research fields in which a researcher works is also positively related to greater productivity, albeit in second- and third-tier publication outlets. In addition, we found that the number of strong ties in the focal author’s professional support network positively related to his or her total citation count, independent of the number and quality of publications. Implications for the social network theory of creativity, organizational knowledge theory, and models of management scholars’ productivity are explored.
High-quality 3-dimensional imaging for patients with anomalous pulmonary veins
Authors: Fukuta Kentaro , Shimada Yoshihisa , Hagiwara Masaru , Kajiwara Naohiro , Ohira Tatsuo , Ikeda Norihiko
Published: August 2014

The branching pattern of pulmonary veins exhibits many variations. Here we describe 2 patients with lung malignancies who were found to have pulmonary vein anomalies. We performed video-assisted thoracoscopic lobectomies based on preoperative simulations by 3-dimensional computed tomography. Using 3-dimensional computed tomography, a surgeon can easily construct digital images of the patient’s pulmonary vessels within a few minutes. Simulation using 3-dimensional computed tomography imaging is useful for further understanding of the surgical anatomy.
Exploring Political Ideologies of Senators With Semantic Analysis Tools
Authors: Holtzman Nicholas S. , Kwong Simon , Baird Kirsten L.
Published: August 2014

Phrase counting is an effective approach to capturing individual differences in language use. Specific phrases (e.g., “war on terrorism”) powerfully predict a congressperson’s political ideology. The question addressed in this study is whether there is additional information that can be extracted from the indirect relations among words in large Senatorial speech databases. Given that direct co-occurrence of target words is a very low likelihood event, we focus on higher-order co-occurrence (e.g., whether two target words appear in similar semantic contexts), using the free software Contrast Analysis of Semantic Similarity (CASS) to compute individual differences ( www.casstools.org ). We describe how we used CASS in detail and provide a tutorial. Using text transcripts from 86 Senators, totaling over 150 million words, we demonstrate that CASS can account for political ideology above and beyond phrase counts. By complementing phrase count methods, CASS may be a useful method for the digital humanities and social sciences more generally.
Central noradrenergic mechanisms and the acute stress response during painful stimulation
Authors: Chapman C Richard , Bradshaw David H , Donaldson Gary W , Jacobson Robert C , Nakamura Yoshio
Published: August 2014

Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain.
CYP2C19 variation, not citalopram dose nor serum level, is associated with QTc prolongation
Authors: Kumar Yingying , Kung Simon , Shinozaki Gen
Published: August 2014

Recently, a FDA Safety Communication warned of a dose-dependent risk for QTc prolongation with citalopram, which is metabolized by CYP2C19 of the cytochrome P450 system. We investigate associations between citalopram and escitalopram dose, serum concentration, CYP2C19 phenotype, and QTc. We undertook a retrospective chart review of citalopram or escitalopram patients with the inclusion criteria of consistent medication dose, CYP2C19 phenotype (extensive metabolizers [EM], intermediate metabolizers [IM], poor metabolizers [PM]), and QTc interval on ECG. We further identified 42 citalopram users with citalopram serum concentration measurements and ECG. Regression and one-way ANOVA were used to examine the relationship between citalopram dose, citalopram serum concentration, CYP2C19 phenotype, and QTc interval. Of 75 citalopram patients, the EM group had significantly shorter QTc intervals than a combined IM+PM group (427.1±23.6 ms vs. 440.1±26.6 ms, one-tailed t-test, p=0.029). In the 80 escitalopram cohort, there was no significant difference in QTc between phenotype groups. There was no statistical correlation between citalopram ( p=0.62) or escitalopram ( p=0.30) dose and QTc. QTc was not associated with citalopram serum level ( p=0.45). In contrast to the FDA warning, this study found no association between citalopram/escitalopram dose and QTc. However, PM of the drug tended to have longer QTc intervals. Our findings suggest cytochrome P450 genotyping in select patients may be helpful to guide medication optimization while limiting harmful effects.
Hippocampal volume and the rapid antidepressant effect of ketamine
Authors: Abdallah Chadi G , Salas Ramiro , Jackowski Andrea , Baldwin Philip , Sato João R , Mathew Sanjay J
Published: August 2014

Accumulating evidence underscores the utility of ketamine in treating severely treatment-resistant depressed patients. We investigated the relationship between the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker of antidepressant treatment outcome. We gave 16 medication-free, major depressive disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5 mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h post-treatment, with the Montgomery-Åsberg Depression Rating Scale (MADRS). Prior to treatment, patients underwent magnetic resonance imaging (MRI) to estimate their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS (post- minus pre-treatment) was significantly correlated with the pre-treatment volumes of the left hippocampus ( r = 0.66; p = 0.01), but not the right hippocampus ( r = 0.49; p = 0.09). The correlation between delta MADRS and the left hippocampus remained high ( r > 0.6; p = 0.13), after controlling for several demographic and clinical variables, although the p value increased due to the reduced degree of freedom ( df = 5). Ketamine exerts enhanced antidepressant effects in patients with a relatively smaller hippocampus, a patient population that has been repeatedly shown to be refractory to traditional antidepressants.
The Intersubjective and Social Unconscious are Inseparable
Authors: Biran Hanni
Published: August 2014

Culture within the analytic group is intersubjective. The matrix includes intense interpersonal events. The drama taking place within the group may be defined as intersubjective. The drama occurring in the multi-dimensional complex of society as a whole may be defined as the social unconscious. The connection between these two dramas is unbreakable. In this article I describe a traumatic event that occurred in the here and now of the group, an event which revived past traumas of patients and conductor alike. The events belong to the wide social context. In the second part of the article I expand upon some aspects of my Jewish and Israeli identity. I describe some childhood memories connected to the Holocaust, and I refer to the way that these memories influence my interventions in my role as a group analyst.