bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-282: Transethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A
Authors: Wang Hansong , Burnett Terrilea , Kono Suminori , Haiman Christopher , Iwasaki Motoki , Wilkens Lynne , Loo Lenora , Berg David Van Den , Kolonel Laurence , Henderson Brian , Keku Temitope , Sandler Robert , Signorello Lisa , Blot William , Newcomb Polly , Pande Mala , Amos Christopher , West Dee , Bézieau Stéphane , Berndt Sonja , Zanke Brent , Hsu Li , Lindor Noralane , Haile Robert , Hopper John , Jenkins Mark , Gallinger Steven , Casey Graham , Stenzel Stephanie , Schumacher Fredrick , Peters Ulrike , Gruber Stephen , Tsugane Shoichiro , Stram Dan , Marchand Loic L.
Published: May 2015

To identify genetic variants that contribute to colorectal cancer (CRC) susceptibility, we performed a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, followed by a replication of genome-wide statistically significant associations (P < 5E-8) in 16,823 cases and 18,211 controls of European ancestry. This study revealed a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.5E-9), providing additional insight into the etiology of CRC and highlighting the value of association mapping in diverse populations.

Citation Format: Hansong Wang, Terrilea Burnett, Suminori Kono, Christopher Haiman, Motoki Iwasaki, Lynne Wilkens, Lenora Loo, David Van Den Berg, Laurence Kolonel, Brian Henderson, Temitope Keku, Robert Sandler, Lisa Signorello, William Blot, Polly Newcomb, Mala Pande, Christopher Amos, Dee West, Stéphane Bézieau, Sonja Berndt, Brent Zanke, Li Hsu, Noralane Lindor, Robert Haile, John Hopper, Mark Jenkins, Steven Gallinger, Graham Casey, Stephanie Stenzel, Fredrick Schumacher, Ulrike Peters, Stephen Gruber, Shoichiro Tsugane, Dan Stram, Loic Le Marchand. Transethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-282. doi:10.1158/1538-7445.AM2014-LB-282
Abstract LB-70: BRCA1 impacts ovarian cancer cell migration through modulating Pfn1 expression
Authors: Gau David M. , Lesnock Jamie , Krivak Thomas , Edwards Robert , Roy Partha
Published: May 2015

Functional loss of BRCA1 has been implicated in genomic instability and cancer progression. A recent study demonstrated that BRCA1 plays a role in cancer cell migration. Using a random cell motility assay, we showed that BRCA1 promotes ovarian cancer cell migration. A proteomics study of BRCA1 +/- cell lines and tissues identified Profilin1 (Pfn1) as one of the differentially expressed proteins. This was further confirmed by Western blot and IHC analyses with tissue samples and cell lines. Pfn1 is an actin cytoskeleton-associated protein which promotes breast cancer cell motility/invasion and dissemination when downregulated. To further study whether BRCA1 impacts cell migration through Pfn1, Pfn1 was silenced which revealed enhanced motility in multiple BRCA1-WT ovarian cancer cell lines. Furthermore, overexpression of Pfn1 in BRCA1 cell lines reduced random motility which further implicates the importance of Pfn1 in ovarian cancer motility. This is the first evaluation of both motility and the functional role of Pfn1 in ovarian cancer cells. While BRCA1 has been extensively studied in the context of DNA repair, there is emerging evidence that BRCA1 proteins may play a role in cell migration. The increased motility seen in wild-type cells compared to BRCA1-mutated cells may portend increased metastatic potential in wild-type cancers. Our findings demonstrate that 1) BRCA1 positively influences ovarian cancer cell motility, and 2) BRCA1 status determines Pfn1's role in ovarian cancer cell motility suggesting a possible novel mechanism association between Pfn1 and BRCA1 and ovarian cancer cell motility. Future studies should explore whether Pfn1 downregulation enhances the metastatic potential of ovarian cancer cells with intact BRCA1 function and whether Pfn1 may serve as a possible therapeutic target.

Citation Format: David M. Gau, Jamie Lesnock, Thomas Krivak, Robert Edwards, Partha Roy. BRCA1 impacts ovarian cancer cell migration through modulating Pfn1 expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-70. doi:10.1158/1538-7445.AM2014-LB-70
Abstract SY04-04: Vitamin D receptor stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy
Authors: Evans Ronald M.
Published: May 2015

The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) is thought to drive the severe stromal reaction that characterizes PDA. Here we reveal that the vitamin D receptor (VDR) is expressed in activated human pancreatic tumor stroma as well as in in vivo models of pancreatitis, a known risk factor for PDA. Notably, treatment with the VDR ligand calcipotriol markedly reduced inflammation and fibrosis during pancreatitis and a more pronounced form of the disease developed in VDR knockout mice. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state such that ligand-induced stromal remodeling increased intratumoral gemcitabine levels 5-fold and reduced tumor volume. This work describes a molecular strategy through which epigenomic reprogramming of pancreatic tumor stroma rescues/fosters a robust chemotherapeutic response and advocates a reevaluation of vitamin D therapy for PDA.

Citation Format: Ronald M. Evans. Vitamin D receptor stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr SY04-04. doi:10.1158/1538-7445.AM2014-SY04-04
Abstract SY21-02: Extracellular matrix density, alignment, and tumor progression
Authors: Keely Patricia J.
Published: May 2015

An increase in the mammographic density of breast tissue is correlated to a four to six-fold increased risk of developing breast carcinoma, making it the single biggest risk factor for breast carcinoma. Increased breast density is associated with a significant increase in the deposition of ECM components, most notably collagen, which leads to an increase in matrix stiffness. In a mouse model of increased collagen deposition, we find that mammary tumor incidence, invasion, and metastasis increased three-fold. Mammary tumors arising in FAK-/- mammary glands were non-invasive and non-metastatic. Gene expression profiling of these tumors identified a metastasis signature regulated by FAK, and further identify novel mechanisms and signaling pathways governing invasion into collagen matrices.

Using state-of-the-art non-linear optical imaging techniques (FLIM and SHG), we have imaged collagen and cells at the tumor-stromal boundary in live, unfixed mammary tumors. We find that during tumor progression, the structure and alignment of collagen fibers is altered, such that the perpendicular realignment of collagen fibers is completely coincident with areas of local invasion. A recent analysis of 207 human samples demonstrates that the presence of perpendicular aligned collagen was a novel significant and independent prognostic indicator of poor patient survival, with a risk factor of 4.3. To determine whether fibril alignment facilitates invasion, we engineered aligned matrices, and found that human breast carcinoma cells preferentially invaded along perpendicularly aligned vs. random or parallel collagen fibers. Our results demonstrate collagen fibers serve as a highway to facilitate local invasion, and promote distal metastasis.

Citation Format: Patricia J. Keely. Extracellular matrix density, alignment, and tumor progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr SY21-02. doi:10.1158/1538-7445.AM2014-SY21-02
Abstract A08: Investigating tumor vasculature development and the effects of OXi4503 by non-invasive photoacoustic imaging
Authors: Johnson Sean Peter , Ogunlade Ollie , Zhang Edward , Lythgoe Mark , Beard Paul , Pedley Rosamund Barbara
Published: May 2015

Vasculature-targeted cancer therapies, such as vascular disrupting or anti-angiogenic agents, interact directly with tumor blood vessels. Direct longitudinal assessment of vascular response, as opposed to indirect measures of tumor volume, would aid clinical translation for these targeted therapies, but novel treatment strategies require adequate biomarkers of response.

OXi4503 (Combretastatin-A1 phosphate, CA1P) is a vascular disrupting agent (VDA) known to have significant antitumor effects against a wide range of pre-clinical human tumor model systems, and in the clinic. OXi4503 causes disruption of the central tumor vasculature within an hour of administration, followed by thrombosis and vessel occlusion, resulting in massive central tumor necrosis 24 hours after treatment but leaving a thin viable rim of tumor cells.

Photoacoustic imaging (PAI) is a novel non-ionising and non-invasive technique, that provides 3D images of the vascular microenvironment with high spatial resolution. Structural information of blood vessel location, and potentially functional data as well, can therefore be obtained in a longitudinal manner. It is thus ideally suited to assess preclinical models of subcutaneous tumors with regard to vascular targeted therapies. We have used PAI to investigate the development of tumor blood vessels, and the effects of OXi4503 (40mg/kg) on the vasculature of 2 human colorectal xenografts grown in nude mice.

Results: The human colorectal tumor cell lines SW1222 and LS174T were established as subcutaneous models in nude mice, by the injection of 5X106 tumor cells.

Using PAI we were able to:

Determine the extent and pattern of tumor vascularization, non-invasively, over time

Differentiate between the pathophysiologies of different tumor types

Follow the response to vascular targeted therapy

Determine the length of time to tumor regrowth following therapy

Conclusion: The data suggest that PAI could prove invaluable in providing imaging biomarkers of response to treatment for vascular targeted therapies, with potential for clinical translation.

Citation Format: Sean Peter Johnson, Ollie Ogunlade, Edward Zhang, Mark Lythgoe, Paul Beard, Rosamund Barbara Pedley. Investigating tumor vasculature development and the effects of OXi4503 by non-invasive photoacoustic imaging. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A08. doi:10.1158/1538-7445.CHTME14-A08
Abstract A65: Heterogeneous response of H460 non-small lung carcinoma cells to CPI-613, a novel compound that selectively alters tumor energy metabolism
Authors: Perera Candida N. , Rodriguez Robert , Shorr Robert
Published: May 2015

Lung cancer is the leading cause of cancer-related death. The high prevalence coupled with the high death rate and current lack of effective therapy against this type of cancer have spurred research on the characteristics of tumor cells and the search for novel strategies to prevent and treat lung cancer. The relationship between the degree of heterogeneity of tumor cells vs. the tumor cells sensitivity to anti-cancer agents may reflect the presence of cancer causing stem cells. The H460 non-small cell lung cancer cell line has been documented to have a great degree of heterogeneity with various degrees of responsiveness to the anti-cancer drug paclitaxel. The objective of this investigation was to assess the phenotypic heterogeneity of the H460 cell line following treatment with CPI-613. CPI-613 is a novel anti-cancer agent that selectively targets the altered form of mitochondrial energy metabolism utilized by tumor cells, that illicit changes in mitochondrial enzyme activities and cellular redox status leading to apoptosis, necrosis, and/or autophagia of tumor cells, without affecting normal cells. Different populations of H460 cells were generated following treatment of these cells with 1-2 rounds of CPI-613. The IC50 for the sub-population of H460 cells was approximately twice higher than that of parent H460 population (52±8 vs. 29±3 μM), suggesting the H460 cell line have CPI-613-sensitive and less sensitive sub-populations. Gene expression profiling revealed a difference in the metabolic and signaling pathways altered by CPI-613 among the different sub-populations. The cellular morphology observed under the microscope and up-regulation of SNAI2 and mesenchymal markers suggested that the sub-population consisted of cells with the epithelial-mesenchymal transition (EMT) phenotype. Recent evidence suggests that cells that undergo EMT gain stem cell-like properties, thus giving rise to cancer stem cells. We were able to demonstrate that treatment of parent H460 cells with CPI-613 at 50 μM for 24 hrs eliminated the sensitive population and treatment for 48 hrs was able to completely eliminate the resistant population containing cells with stem cell-like properties.

Citation Format: Candida N. Perera, Robert Rodriguez, Robert Shorr. Heterogeneous response of H460 non-small lung carcinoma cells to CPI-613, a novel compound that selectively alters tumor energy metabolism. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A65. doi:10.1158/1538-7445.CHTME14-A65
Abstract B10: LFA-1/ICAM-1 interaction switches on an orchestrated prometastatic microenvironmental shift during experimental liver metastasis of colon C26 cancer cells.
Authors: Benedicto Aitor , Marquez Joana , Olaso Elvira , Arteta Beatriz
Published: May 2015

Intercellular adhesion molecule (ICAM)-1 is the main counter-receptor for the lymphocyte function associated antigen (LFA)-1. However, the role this interaction plays during liver metastasis of colorectal cancer cells and its underlying mechanisms remain unclear. Previously, we showed that mannose receptor (ManR) stimulation on liver sinusoidal endothelial cells (LSECs) resulted in a reduced cytotoxic potential of liver infiltrating lymphocytes (LIL) towards C26 murine colon carcinoma cells.

Using ICAM-1 specific siRNAs in vivo, we aimed to study the role of hepatic ICAM-1 in the prometastatic shift of the liver microenvironment. Livers of control and silenced mice, 24 hours and 14 days after C26 cell inoculation, were compared for: percentage of detained C26 cells, number and volume of metastatic foci, levels of recruited immune, myofibroblastic and inflammatory cells and whole liver expression of pro-inflammatory genes.

Detained cancer cells and metastatic foci number were reduced in silenced mice compared to controls, along with a decrease in myeloid suppressor cells and recruited macrophages and myofibroblasts. On the contrary, significant higher numbers of lymphocytic cells were observed in mice with reduced ICAM-1. Finally, silencing of ICAM1 resulted in altered total liver mRNA levels of proinflammatory factors in the tumor-bearing mice.

Therefore, an orchestrated prometastatic program might be switched on in the liver microenvironment by LFA-1/ICAM-1 interaction which, in turn, could lead not only to a reduced antitumor citotoxicity but, also, to activation of the stromal compartment favoring tumor progression, and, opening liver's doors to tumor cells to aggressively metastasize. Based on these results, LFA-1/ICAM-1 interaction arises as a potential therapeutic target in cancer treatment.

Citation Format: Aitor Benedicto, Joana Marquez, Elvira Olaso, Beatriz Arteta. LFA-1/ICAM-1 interaction switches on an orchestrated prometastatic microenvironmental shift during experimental liver metastasis of colon C26 cancer cells.. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B10. doi:10.1158/1538-7445.CHTME14-B10
Abstract B16: Progastrin activates colon fibroblasts and participates to the dialogue between tumor epithelial cells and stromal fibroblasts in colorectal cancer
Authors: Fénié Nicolas , Bertrand Claudine , Lacombe Aurélien , Roche Serge , Bousquet Corinne , Gouazé-Andersson Valérie , Toulas Christine , Moyal Elizabeth , Ferrand Audrey
Published: May 2015

Colorectal cancer (CRC) represents the second leading cause of cancer-related death worldwide. One of the main reasons for this high mortality rate is because CRC develops into invasive lesions with high metastasis potential. The cancer-associated fibroblasts (CAFs) present in the tumour reactive stroma promote epithelial cancer cell motility and aggressiveness. However, whereas the role of tumour-stroma crosstalks in cancer progression is increasingly documented, how “normal” resident fibroblasts are converted into pro-invasive CAFs and how CAFs participate to the epithelial-stroma dialogue remains an open question. Precursor of the hormone gastrin, progastrin, now established as a growth factor for colon cells, is detected in colorectal polyps and tumours while it is absent in healthy colon.

Using immunohistochemical and biochemical approaches we found that progastrin induces the expression of fibroblast activation markers (alphaSMA, FAPalpha) in the normal colon mucosa of progastrin-overexpressing mice as well as in the human colon fibroblast cell line CCD18Co. To investigate the role of progastrin-induced fibroblast activation, we compared the migration of colon epithelial cancer cells expressing or not the hormone in presence or absence of fibroblasts in Boyden chamber. Progastrin-expressing epithelial cells have increased migration capacities in presence of fibroblasts while not difference between the two epithelial cell lines was observed in absence of fibroblasts. Moreover, we identified the implication of different chemokines in this process.

Thus, here we demonstrate that progastrin, secreted by tumour epithelial cells, contributes to the activation of the fibroblasts present in the cancer-associated stroma and participates to the epithelial-stroma dialogue.

Citation Format: Nicolas Fénié, Claudine Bertrand, Aurélien Lacombe, Serge Roche, Corinne Bousquet, Valérie Gouazé-Andersson, Christine Toulas, Elizabeth Moyal, Audrey Ferrand. Progastrin activates colon fibroblasts and participates to the dialogue between tumor epithelial cells and stromal fibroblasts in colorectal cancer. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B16. doi:10.1158/1538-7445.CHTME14-B16
Deficiency in Melanocortin 1 Receptor Signaling Predisposes to Vascular Endothelial Dysfunction and Increased Arterial Stiffness in Mice and Humans
Authors: Rinne Petteri , Ahola-Olli Ari , Nuutinen Salla , Koskinen Emilia , Kaipio Katja , Eerola Kim , Juonala Markus , Kähönen Mika , Lehtimäki Terho , Raitakari Olli T. , Savontaus Eriika
Published: May 2015

Objective—

The melanocortin 1 receptor (MC1-R) is expressed by vascular endothelial cells and shown to enhance nitric oxide (NO) availability and vasodilator function on pharmacological stimulation. However, the physiological role of MC1-R in the endothelium and its contribution to vascular homeostasis remain unresolved. We investigated whether a lack of functional MC1-R signaling carries a phenotype with predisposition to vascular abnormalities.

Approach and Results—

Recessive yellow mice (MC1R
e/e
), deficient in MC1-R signaling, and their wild-type littermates were studied for morphology and functional characteristics of the aorta. MC1R
e/e
mice showed increased collagen deposition and arterial stiffness accompanied by an elevation in pulse pressure. Contractile capacity and NO-dependent vasodilatation were impaired in the aorta of MC1R
e/e
mice supported by findings of decreased NO availability. These mice also displayed elevated levels of systemic and local cytokines. Exposing the mice to high-sodium diet or acute endotoxemia revealed increased susceptibility to inflammation-driven vascular dysfunction. Finally, we investigated whether a similar phenotype can be found in healthy human subjects carrying variant
MC1-R
alleles known to attenuate receptor function. In a longitudinal analysis of 2001 subjects with genotype and ultrasound data (The Cardiovascular Risk in Young Finns Study), weak MC1-R function was associated with lower flow-mediated dilatation response of the brachial artery and increased carotid artery stiffness.

Conclusions—

The present study demonstrates that deficiency in MC1-R signaling is associated with increased arterial stiffness and impairment in endothelium-dependent vasodilatation, suggesting a physiological role for MC1-R in the regulation of arterial tone.
Choline Transporter-Like Protein-2
Authors: Bayat Behnaz , Tjahjono Yudy , Berghöfer Heike , Werth Silke , Deckmyn Hans , De Meyer Simon F. , Sachs Ulrich J. , Santoso Sentot
Published: May 2015

Objective—

In contrast to other antibodies involved in transfusion-related acute lung injury, anti–HNA-3a antibodies are incapable of inducing direct neutrophil activation and seem to interact with endothelial cells (ECs) primarily. In animal studies, anti–HNA-3a-mediated transfusion-related acute lung injury could be precipitated in the absence of neutrophils, but was stronger when neutrophils were present. In a different context the target protein of these antibodies, choline transporter-like protein-2 (CTL-2), was reported to interact with a protein of the inner ear carrying 2 von Willebrand factor (VWF) A-domains. These observations prompted us to investigate whether VWF might be involved in anti–HNA-3a-mediated neutrophil activation, and whether signaling via CD11b/CD18 is involved, as in various other experimental settings.

Approach and Results—

Cell adhesion demonstrated specific binding of CTL-2 to VWF. Immunoprecipitation analysis of CTL-2/CD11b/CD18 coexpressing cells indicated that anti–HNA-3a colocalizes CTL-2 and CD11b/CD18 when VWF is present. Functional studies revealed that anti–HNA-3a-mediated neutrophil agglutination is an active, protein kinase C-dependent and partially Fc-dependent process. Agglutination and the production of reactive oxygen species seem to require the formation of a trimolecular complex between the target antigen (CTL-2), CD11b/CD18 and VWF. In line with these observations, anti–HNA-3a induced less severe transfusion-related acute lung injury and less neutrophil recruitment to the alveolar space in VWF knockout mice.

Conclusions—

We introduce CTL-2 as a new binding partner for VWF. Interaction of neutrophils with VWF via CTL-2 allows anti–HNA-3a to induce signal transduction via CD11b/CD18, which leads to neutrophil activation and agglutination. In transfusion-related acute lung injury, this mechanism may further aggravate endothelial leakage.
Effects of Postinfarct Myelin-Associated Glycoprotein Antibody Treatment on Motor Recovery and Motor Map Plasticity in Squirrel Monkeys
Authors: Barbay Scott , Plautz Erik J. , Zoubina Elena , Frost Shawn B. , Cramer Steven C. , Nudo Randolph J.
Published: May 2015

Background and Purpose—

New insights into the brain’s ability to reorganize after injury are beginning to suggest novel restorative therapy targets. Potential therapies include pharmacological agents designed to promote axonal growth. The purpose of this study was to test the efficacy of one such drug, GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule, myelin-associated glycoprotein, to facilitate recovery of motor skills in a nonhuman primate model of ischemic cortical damage.

Methods—

Using a between-groups repeated-measures design, squirrel monkeys were randomized to 1 of 2 groups: an experimental group received intravenous GSK249320 beginning 24 hours after an ischemic infarct in motor cortex with repeated dosages given at 1-week intervals for 6 weeks and a control group received only the vehicle at matched time periods. The primary end point was a motor performance index based on a distal forelimb reach-and-retrieval task. Neurophysiological mapping techniques were used to determine changes in spared motor representations.

Results—

All monkeys recovered to baseline motor performance levels by postinfarct day 16. Functional recovery in the experimental group was significantly facilitated on the primary end point, albeit using slower movements. At 7 weeks post infarct, motor maps in the spared ventral premotor cortex in the experimental group decreased in area compared with the control group.

Conclusions—

GSK249320, initiated 24 hours after a focal cortical ischemic infarct, facilitated functional recovery. Together with the neurophysiological data, these results suggest that GSK249320 has a substantial biological effect on spared cortical tissue. However, its mechanisms of action may be widespread and not strictly limited to peri-infarct cortex and nearby premotor areas.
Diagnostic Work-Up for Detection of Paroxysmal Atrial Fibrillation After Acute Ischemic Stroke
Authors: Rizos Timolaos , Quilitzsch Anika , Busse Otto , Haeusler Karl Georg , Endres Matthias , Heuschmann Peter , Veltkamp Roland
Published: May 2015

Background and Purpose—

Multiple methods to detect paroxysmal atrial fibrillation (pAF) in patients with acute stroke are available. However, it is unknown which approaches are currently used in clinical routine and guidelines remain vague to the extent of cardiac monitoring. We characterize diagnostic efforts for pAF detection on German stroke units (SU).

Methods—

A standardized anonymous questionnaire was sent to all clinical leads of certified SUs in Germany. The questionnaire focused on basic characteristics of SUs, procedures to detect AF, and estimates on AF detection.

Results—

One hundred seventy-nine SU leads participated (response rate 71.6%). All patients undergo continuous bedside ECG monitoring. A percentage of 77.6 SUs initiate additional 24-hour Holter ECG in >50% of patients without known AF. Patients with transient ischemic attack are monitored significantly shorter than patients with ischemic stroke. Independent of SU type or size, 67.6% of leads assumed to fail detecting pAF in 5% to 20% of patients. In cryptogenic stroke, additional ECG monitoring is recommended by 90.2% but only 13.8% of SUs perform routine ECG follow-up visits. The use of implanted event recorders is low (1–10 patients/y by 60.7% of SUs; 28.1%: no use). A percentage of 83.9 do not use external event recorders.

Conclusions—

Our survey demonstrates substantial heterogeneity among German SUs on diagnostic work-up for pAF. Future prospective multicenter studies should systematically evaluate the impact of different methods to uncover pAF.
Does Shortening the School Week Impact Student Performance? Evidence from the Four-Day School Week
Authors: Anderson D. Mark , Walker Mary Beth
Published: May 2015

School districts use a variety of policies to close budget gaps and stave off teacher layoffs and furloughs. More schools are implementing four-day school weeks to reduce overhead and transportation costs. The four-day week requires substantial schedule changes as schools must increase the length of their school day to meet minimum instructional hour requirements. Although some schools have indicated this policy eases financial pressures, it is unknown whether there is an impact on student outcomes. We use school-level data from Colorado to investigate the relationship between the four-day week and academic performance among elementary school students. Our results generally indicate a positive relationship between the four-day week and performance in reading and mathematics. These findings suggest there is little evidence that moving to a four-day week compromises student academic achievement. This research has policy relevance to the current U.S. education system, where many school districts must cut costs.
The Myth of Entangling Alliances: Reassessing the Security Risks of U.S. Defense Pacts
Authors: Beckley Michael
Published: May 2015

A large literature assumes that alliances entangle the United States in military conflicts that it might otherwise avoid. Since 1945, however, there have been only five cases of what might be characterized as U.S. entanglement—the 1954 and 1995–96 Taiwan Strait crises, the Vietnam War, and the interventions in Bosnia and Kosovo in the 1990s—and even these cases are far from clear-cut. U.S. entanglement is rare because the United States, as a superpower with many allies, is capable of exploiting loopholes in alliance agreements, sidestepping commitments that seriously imperil U.S. interests, playing the demands of various allies off of each other, and using alliances to deter adversaries and allies from initiating or escalating conflicts.
Concessions or Coercion? How Governments Respond to Restive Ethnic Minorities
Authors: Grigoryan Arman
Published: May 2015

Destabilized multiethnic states and empires are environments that are highly susceptible to violent ethnonationalist conflict. Conflicts between states built on the ruins of such empires and their minorities are especially common. James Fearon has famously argued that these conflicts are the result of minorities' rational incentives to rebel, which in turn are the result of newly independent states' inability to guarantee that these minorities will not be discriminated against if they acquiesce to citizenship, as well as expectations that over time the balance of power will shift against minorities as states consolidate their institutions. States can, however, take steps to reassure their minorities. The puzzle is why they often fail to do so. In fact, states often adopt policies that confirm minorities' worst fears, pushing them toward rebellion. Such action may be precipitated by a state's belief that a minority is motivated by a separatist agenda rather than by the desire to have its concerns and grievances satisfactorily addressed. If secession is a minority's primary objective, then concessions intended to demobilize the minority will only make the state more vulnerable to future demands and separatist bids. The existence of third parties with incentives to support minority separatism exacerbates the problem. The violent and nonviolent minority disputes in post-Soviet Georgia illustrate these findings.
Der Stoiker Mnesarch als Lehrer des Antiochus im Index Academicorum
Authors: Fleischer Kilian
Published: May 2015

A new reading in Philodemus’ Index Academicorum (PHerc. 1021, col. xxxiv, ll. 22-24) attests that Antiochus of Ascalon was a pupil of the Stoic Mnesarch and resolves the last remaining doubts about the real existence of this relationship.
Talking with al Qaeda: Is There a Role for Track Two?
Authors: Jones Peter
Published: May 2015

Despite saying that they will never “talk to terrorists,” many countries have done so. Often these dialogues have included a component of so-called “Track Two Diplomacy.” This article examines whether such a dialogue could be held with al Qaeda and other such groups. Research demonstrates that dialogues have been useful in ending terror campaigns in certain circumstances, but that they were never the decisive element. Where they have been useful, dialogues have helped to distinguish those members of terror organizations who are willing to talk from the hardliners, in helping to develop ‘acceptable’ players on the other side, and in allowing the two sides to better understand each other. The article finds that a dialogue with the hard core of al Qaeda is likely impossible, but that some elements may be willing to talk. Such dialogues will be localized and will be about specific concerns and, like in other cases, will be about seeing if there are elements of the movement that can be detached from the hard-core base. Track Two may have a role to play in these dialogues, but expectations should be kept modest.
The Triumph of Agency over Structure: Shimon Peres and the Israeli Nuclear Program
Authors: Ziv Guy
Published: May 2015

This article advances the proposition that when the negotiator is empowered to reach an agreement on behalf of his or her government, agency has the potential to triumph over structure. The negotiator whose personal attributes include flexibility, sensitivity, inventiveness, tenacity and patience is more likely to meet this potential. Shimon Peres, the director-general of Israel’s Ministry of Defense in the mid-1950s, possessed many of these traits. He was also given virtually free rein by Prime Minister and Defense Minister David Ben-Gurion to pursue negotiations with France over the acquisition of a nuclear reactor. Despite significant structural hurdles – financial difficulties, domestic opposition, u.s. disapproval, and an unstable and divided French Fourth Republic – Peres’s unorthodox diplomacy allowed Israel to become a nuclear power. This case highlights the oft-overlooked role of agency in political science, in general, and in international negotiations, in particular.
Using Momentum Analysis to Explain and Forecast the Outcome of International Negotiations
Authors: Bjola Corneliu
Published: May 2015

Drawing on the literature of technical analysis in financial markets, this article introduces an original framework and methodology for explaining and forecasting the outcome of international negotiations based on two concepts: the relative strength negotiation index (rsni) and the negotiation contextual conduciveness index (ncci). By comparing the parties’ levels of interest in the negotiations, rsni serves as a powerful indicator of the direction and intensity of the momentum accompanying international negotiations. ncci, on the other hand, helps to explain why certain potential breakthroughs may fail to materialize. These insights are being asessed empirically in the case of climate change negotiations, first, by testing retrospectively the viability of the model to explain the outcomes of past climate meetings and, second, by forecasting the likelihood that a breakthrough will be achieved in the next rounds of climate talks.
Canada’s Multiple Voices Diplomacy in Climate Change Negotiations: A Focus on Québec
Authors: Chaloux Annie , Paquin Stéphane , Séguin Hugo
Published: May 2015

This article sheds light on the complexity of international climate change negotiations in a federal country, like Canada, where there is no clear attribution of full power over international negotiation concerning this issue. Climate change is a multi-level and multi-stakeholder issue, one that can only be tackled successfully if all actors, at all levels of government, are involved in the process. In recent years, Canadian provinces, especially Québec, have become intensely involved in climate change paradiplomacy. That situation has led to a Canadian paradox where the Government of Québec worked to respect the Kyoto Protocol and act accordingly, while Canada opted out of the Protocol in 2011.
Nature and Artifice in Hobbes’s International Political Thought
Authors: Jaede Maximilian
Published: May 2015

This article argues that the artificiality of Hobbesian states facilitates their coexistence and eventual reconciliation. In particular, it is suggested that international relations may be characterised by an artificial equality, which has a contrary effect to the natural equality of human beings. Unlike individuals in Hobbes’s account of the state of nature, sovereigns are not compelled to wage war out of fear and distrust, but have prudential reasons to exercise self-restraint. Ultimately rulers serve as disposable figureheads who can be replaced by a foreign invader. Thus, this article highlights the implications of Hobbes’s views on sovereignty by acquisition, which allow for states to be decomposed and reassembled in order to re-establish lasting peace. It is concluded that these findings help to explain why Hobbes does not provide something akin to modern theories of international relations, as foreign affairs appear to be reducible to a matter of either prudence or political philosophy.
Towards a Post-Hobbesian Political Community?
Authors: Sergei Prozorov
Published: May 2015

The article addresses the attempts of contemporary continental philosophy to develop a politics that would move beyond the Hobbesian logic of the constitution of political community. In their readings of Hobbes, Roberto Esposito and Giorgio Agamben emphasize the nihilistic character of Hobbes’s approach to community. For Esposito, Hobbes’s commonwealth is legitimized by a prior negation of the originary human community in the construction of the state of nature as the state of war. Yet, as Agamben shows, this negative state of nature is never fully transcended by the commonwealth, which persistently reproduces it in the state of exception. These critiques emphasize the complex relation between nature and artifice in Hobbes’s thought, which have profound implications for the attempts to arrive at a ‘post-Hobbesian’ mode of political community. Neither a facile search for a truer, more fundamental state of nature nor an affirmation of artifice and denaturation as constitutive of human community are sufficient to evade the Hobbesian constellation. A genuine move beyond Hobbes would rather consist in thoroughly deactivating the very relation between nature and artifice whereby they become indistinct and no longer negate each other.
Vision and Haptics Share Spatial Attentional Resources and Visuotactile Integration Is Not Affected by High Attentional Load
Authors: Wahn Basil , Wahn Basil , König Peter
Published: May 2015

Human information processing is limited by attentional resources. Two questions that are discussed in multisensory research are (1) whether there are separate spatial attentional resources for each sensory modality and (2) whether multisensory integration is influenced by attentional load. We investigated these questions using a dual task paradigm: Participants performed two spatial tasks (a multiple object tracking [‘MOT’] task and a localization [‘LOC’] task) either separately (single task condition) or simultaneously (dual task condition). In the MOT task, participants visually tracked a small subset of several randomly moving objects. In the LOC task, participants either received visual, tactile, or redundant visual and tactile location cues. In the dual task condition, we found a substantial decrease in participants’ performance and an increase in participants’ mental effort (indicated by an increase in pupil size) relative to the single task condition. Importantly, participants performed equally well in the dual task condition regardless of whether they received visual, tactile, or redundant multisensory (visual and tactile) location cues in the LOC task. This result suggests that having spatial information coming from different modalities does not facilitate performance, thereby indicating shared spatial attentional resources for the tactile and visual modality. Also, we found that participants integrated redundant multisensory information optimally even when they experienced additional attentional load in the dual task condition. Overall, findings suggest that (1) spatial attentional resources for the tactile and visual modality overlap and that (2) the integration of spatial cues from these two modalities occurs at an early pre-attentive processing stage.
The Mechanisms of Size Constancy
Authors: Sperandio Irene , Sperandio Irene , Chouinard Philippe A.
Published: May 2015

Size constancy is the result of cognitive scaling operations that enable us to perceive an object as having the same size when presented at different viewing distances. In this article, we review the literature on size and distance perception to form an overarching synthesis of how the brain might combine retinal images and distance cues of retinal and extra-retinal origin to produce a perceptual visual experience of a world where objects have a constant size. A convergence of evidence from visual psychophysics, neurophysiology, neuropsychology, electrophysiology and neuroimaging highlight the primary visual cortex (V1) as an important node in mediating size–distance scaling. It is now evident that this brain area is involved in the integration of multiple signals for the purposes of size perception and does much more than fulfil the role of an entry position in a series of hierarchical cortical events. We also discuss how information from other sensory modalities can also contribute to size–distance scaling and shape our perceptual visual experience.
Plasticity, and Its Limits, in Adult Human Primary Visual Cortex
Authors: Haak Koen V. , Haak Koen V. , Morland Antony B. , Haak Koen V. , Morland Antony B. , Engel Stephen A.
Published: May 2015

There is an ongoing debate about whether adult human primary visual cortex (V1) is capable of large-scale cortical reorganization in response to bilateral retinal lesions. Animal models suggest that the visual neural circuitry maintains some plasticity through adulthood, and there are also a few human imaging studies in support this notion. However, the interpretation of these data has been brought into question, because there are factors besides cortical reorganization, such as the presence of sampling bias and/or the unmasking of task-dependent feedback signals from higher level visual areas, that could also explain the results. How reasonable would it be to accept that adult human V1 does not reorganize itself in the face of disease? Here, we discuss new evidence for the hypothesis that adult human V1 is not as capable of reorganization as in animals and juveniles, because in adult humans, cortical reorganization would come with costs that outweigh its benefits. These costs are likely functional and visible in recent experiments on adaptation — a rapid, short-term form of neural plasticity — where they prevent reorganization from being sustained over the long term.
Bernhard Sabel and ‘Residual Vision Activation Theory’: a History Spanning Three Decades
Authors: Turco Simona , Turco Simona , Albamonte Emilio , Turco Simona , Albamonte Emilio , Ricci Daniela , Turco Simona , Albamonte Emilio , Ricci Daniela , Fortini Stefania , Turco Simona , Albamonte Emilio , Ricci Daniela , Fortini Stefania , Amore Filippo Maria
Published: May 2015

This review has the purpose of retracing the work of Professor Bernard Sabel and his group over the last 2–3 decades, in order to understand how they achieved formulation of the ‘Residual Vision Activation Theory’. The methodology proposed is described, from the first studies in 1995 with High Resolution Perimetry requiring a six-months training period, to the new technologies, such as repetitive transorbital Alternating Current Stimulation, that require ten days of training. Vision restoration therapy has shown improvement in visual responses irrespective of age at the training, lesion aetiology and site of lesion. The hypothesis that visual training may induce network plasticity, improving neuronal networks in cortical and subcortical areas of both hemispheres, appears to be confirmed by recent studies including observation of the cerebral activity by fMRI and EEG. However, the results are quite variable and the mechanisms that influence cerebral activity are still unclear. The residual vision activation theory has been much criticized, both for its methodology and analysis of the results, but it gave a new impulse to the research in this area, stimulating more studies on induced cerebral plasticity.
Three new species of Craterispermum (Rubiaceae) from Madagascar
Authors: De Block Petra , Randriamboavonjy Tianjanahary
Published: May 2015

The Afro-Madagascan genus Craterispermum (Craterispermeae, Rubiaceae) is taxonomically badly known. Hitherto, no species were described from Madagascar, although several taxa occur in the humid lowland forests in the eastern and northern regions of the island. In this contribution three new Madagascan Craterispermum species are described, C. motleyanum, C. puffianum and C. cervicorne. All are illustrated and their distribution is discussed. An identification key for the three new species is given.
Carajasia (Rubiaceae), a new and endangered genus from Carajás mountain range, Pará, Brazil
Authors: Salas Roberto Manuel , VIANA PEDRO L. , CABRAL ELSA L. , DESSEIN STEVEN , JANSSENS STEVEN
Published: May 2015

Carajasia is described as a new genus of Rubiaceae. It is so far known only from the mountain summits of Serra dos Carajás (Pará, Brazil), where it is part of a shrubby vegetation surrounded by tropical rainforest. The new genus belongs to the tribe Spermacoceae and is positioned within it to the Spermacoce clade. Carajasia is unique within the clade in having a very particular combination of characters: flowering branches with two axillary flowers per node, homostylous flowers, corollas with a fringe of moniliform hairs, pubescent styles with distinct stigma lobes, bilobed nectariferous discs covered by triangular papillae, pollen with a double reticulum and fruits with a peculiar type of dehiscence. A detailed description of Carajasia is presented, including observations of the fruit and pollen, along with distribution maps and images of the plant in its habitat. A dichotomous key to distinguish Carajasia from other genera with deeply divided stigmas is provided. A molecular phylogenetic study was carried out using ITS and ETS sequences to determine the phylogenetic position of the new genus within the Spermacoce clade. The results of the combined analyses demonstrated that Carajasia is sister to Galianthe with moderate to high support. Both genera form a weakly supported clade with Schwendenera. This clade is sister to the other genera of the Spermacoce clade studied in this work. Galianthe and Schwendenera share with Carajasia pollen with a double reticulum, but they are clearly differentiated by suffruticose habit, heterostylous flowers and the pattern of fruit dehiscence. To clarify the phylogenetic position of Carajasia, some morphological characters are discussed based on the molecular results: division of the stigma, pollen types and floral syndrome.
Hedyotis nanlingensis (Rubiaceae), a new species from South China
Authors: Wang Ruijiang , Deng Shujun , Huang Xiangxu
Published: May 2015

A new species, Hedyotis nanlingensis from Guangdong province, China, is described and illustrated. It is morphologically similar to H. nankunshanensis but differs in the smaller and more slender habit, the sessile leaves, the usually two to three secondary veins on each side of the midvein, the inflorescences with monochasial branching and the shorter style in the long-styled flowers. DNA barcoding analysis demonstrates that all accessions from H. nanlingensis form a monophyletic lineage closely related to H. cantoniensis.