bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation
Authors: Steinberg Benjamin A. , Holmes DaJuanicia N. , Piccini Jonathan P. , Ansell Jack , Chang Paul , Fonarow Gregg C. , Gersh Bernard , Mahaffey Kenneth W. , Kowey Peter R. , Ezekowitz Michael D. , Singer Daniel E. , Thomas Laine , Peterson Eric D. , Hylek Elaine M. ,   The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Investigators and Patients
Published: November 2013

Background

Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown.

Methods and Results

We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974
atrial fibrillation
patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years,
P
<0.0001), more likely to be white (92% versus 89%,
P
=0.005), more likely to have private insurance (33% versus 25%,
P
<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%,
P
<0.0001). They had more new‐onset
atrial fibrillation
(8.8% versus 4.1%,
P
<0.0001), lower
CHADS
2
scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3,
P
<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8,
P
<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73,
P
=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4,
P
<0.0001).

Conclusions

Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted.

Clinical Trial Registration

URL
: Clinicaltrials.gov. Unique identifier:
NCT
01165710.
My Reference Is Prejudiced: David Lamelas's Publication
Authors: Quiles Daniel R.
Published: November 2013

This article addresses David Lamelas's 1970 work Publication, arguing that it represents a subtle critique of the internationalization of conceptual art by a recent entrant into the West European milieu. Exhibited at Nigel Greenwood Gallery in London after the artist's 1968 relocation from Argentina, Publication consists of thirteen written responses to three statements about the possible use of “language as an Art Form” that were sent by Lamelas to international figures in conceptual art such Daniel Buren, Gilbert and George, Lucy Lippard, and Lawrence Wiener. A close reading of this and others of Lamelas's experiments works leading up to this moment reveals affinities with earlier artistic experiments in Buenos Aires, the artist's original context, that have anything but membership in a preexisting movement or the adoption of an established genre as their goal. Between the years 1965 and 1968, Lamelas was part of a group of artists associated with the Torcuato di Tella Institute and the writer Oscar Masotta, who advocated an analytical and antagonistic “dematerialization,” in which prevailing tendencies were to be systematically examined, voided from within, and superseded. In Buenos Aires, Lamelas experimented with breaking his works into sections as a way of calling attention to given objects of attention—a practice of “signaling” that is also present in Publication. Invariably, these works were positioned in critical relationship to those of his peers, applying Masotta's model to each new milieu. In what follows, I compare select works of Lamelas with his contemporaries in Buenos Aires and abroad between 1964 and 1970, contending that Publication represents one of the first appearances of a specifically Argentine, and highly critical, mode of conceptualism in the international art field.
No evidence of selection by predators on tadpole boldness
Authors: Carlson Bradley E. , Langkilde Tracy
Published: November 2013

Animals typically exhibit adaptive behaviors that reduce their risk of predation. The term ‘boldness’ describes individual variation in the propensity to exhibit risk-reducing behavior and is the subject of much research attention. Predators should select against boldness, and this has been supported by empirical studies and behavioral ecology theory. We tested whether a standardized assay of three boldness-associated behaviors in wood frog (Lithobates sylvaticus) tadpoles predicted survival when faced with a predator. Tadpole behavior was assayed in an open field and then tadpoles were placed, in pairs, in an enclosure with a predator (newt or larval dragonfly). Survival did not depend on differences in measured boldness, and this result held when we accounted for interactions between different boldness behaviors and between behavior and size or predator identity. The absence of selection by predators against bolder tadpoles is counterintuitive and inconsistent with our understanding of the behavioral ecology of these animals. Two possible explanations are offered for this result. First, selection against boldness may be minimized by other phenotypic traits, such as escape ability. Alternatively, the potential lack of consistency between standardized boldness assays and natural encounters with predators may limit our capacity to study the evolution of boldness, cautioning against this approach. These results highlight the complexities of the relationships between behavioral traits and fitness and the challenges associated with their study.
Strategic and tactical fighting decisions in cichlid fishes with divergent social systems
Authors: Hick Kristina , Reddon Adam R. , O’Connor Constance M. , Balshine Sigal
Published: November 2013

The costs and benefits of engaging in a contest will differ depending on the social situation of the individuals involved. Therefore, understanding contest behaviour can help to elucidate the trade-offs of living in differing social systems and shed light on the evolution of social behaviour. In the current study, we compared contest behaviour in two closely related species of Lamprologine cichlid fish. Neolamprologus pulcher and Telmatochromis temporalis are both pair-breeding cichlids, but N. pulcher are highly social, group-living fish, while T. temporalis display no grouping behaviour. To examine how competition varies by species, sex and familiarity, we staged same-sex conspecific contests over a shelter, a resource that is highly valued by both species, where contestants were either familiar or unfamiliar to one another. When we examined tactical and strategic components of these contests, we found that the highly social species had shorter contests and engaged in fewer costly aggressive acts than did the non-social species. Individuals of the highly social species were also more likely to resolve conflicts through the use of submissive displays, while individuals of the non-social species were more likely to flee from conflict. Familiarity increased the use of submissive displays in the highly social species but not in the less social species. Our findings suggest that conflict resolution behaviour and dominance hierarchy formation are fundamentally linked to the evolution of complex social systems.
The determinants of dominance relationships among subordinate females in the cooperatively breeding meerkat
Authors: Thavarajah N.K. , Fenkes M. , Clutton-Brock T.H.
Published: November 2013

In cooperatively breeding species with high reproductive skew, a single breeding female is dominant to all other group members, but it is not yet known if there are consistent dominance relationships among subordinates. In this study on meerkats (Suricata suricatta), we used naturally observed dominance assertions and submissive interactions within dyads of subordinate females to investigate: (i) whether or not a dominance structure exists among them and what factors influence dominance relationships; and (ii) how dominance may influence the future reproductive success of subordinate females. Our study indicates that superiority in age and weight provide a competitive advantage during conflicts among subordinate females and that females who consistently dominate in these contests are subsequently more likely to attain a dominant breeding position. This provides a starting point for further investigations into dominance structure among subordinates in meerkat societies and other cooperative breeders.
The genus Xylaria (Xylariaceae) in the south of China—6. A new Xylaria species based on morphological and molecular characters
Authors: MA HAI-XIA , VASILYEVA LARISSA , LI YU
Published: November 2013

Xylaria fusispora, an undescribed species of Xylaria (Xylariales, Xylariaceae), is described and illustrated as a new species based on collections from Guizhou Province, China. Both morphology and phylogenetic analysis of nrDNA ITS sequences support the establishment of this new species. The fungus is characterized by its fusoid-equilateral ascospores and an ascus apical ring not bluing in Melzer’s reagent. The differences between the new species and the related fungi are discussed.
Nematodes from galls on Myrtaceae. V. Fergusobia from large multilocular shoot bud galls from Angophora and Eucalyptus in Australia, with descriptions of six new species
Authors: Davies KERRIE A. , Giblin-Davis ROBIN M. , YE WEIMIN , LISNAWITA LISNAWITA , TAYLOR GARY S. , W. THOMAS KELLEY
Published: November 2013

Six new species of Fergusobia, from large multilocular shoot bud galls on two species of Angophora and four species of Eucalyptus from both subgenera Eucalyptus and Symphyomyrtus, are described. Fergusobia cosmophyllae Davies n. sp. is characterized by the combination of a C-shaped parthenogenetic female with a short arcuate conoid tail, a broad (small a ratio) arcuate infective female with an hemispherical tail tip, and an arcuate to J-shaped male with broad, angular spicules and short bursa.  Fergusobia delegatensae Davies n. sp. has an open C-shaped parthenogenetic female with a broadly conoid tail, an infective female of variable shape with an hemispherical tail tip, and a male of open C-shape with a crenate bursa that arises 40–70% along the length of the body from the tail tip and terminates just anterior to the cloaca. Fergusobia diversifoliae Davies n. sp. has a C-shaped parthenogenetic female with a conoid tail, an arcuate infective female with a hemispherical tail tip, and an arcuate, C- or J-shaped male with angular spicule and a long peloderan bursa. Fergusobia floribundae Davies n. sp. has a C-shaped parthenogenetic female with a narrow, arcuate, conoid tail, an arcuate infective female with a hemispherical tail tip, and an arcuate or J-shaped male with an angular spicule and a short to mid-body length peloderan bursa. Fergusobia minimus Lisnawita n. sp. has a C-shaped parthenogenetic female with a conoid tail, an arcuate to open C-shaped infective female with a hemispherical tail tip, and an arcuate to open C-shaped male with an angular spicule and a peloderan bursa arising at about 10–30% of body length. Fergusobia pimpamensis Davies n. sp. has an open C to C-shaped parthenogenetic female with a narrow conoid tail, an arcuate to open C-shaped infective female with a hemispherical tail tip, and an arcuate to C-shaped male with an arcuate spicule and a long, crenate, peloderan bursa. An inventory of all known Fergusobia/Fergusonina associations from terminal shoot bud galls is presented. The larval shield morphology of the associated mutualistic Fergusonina species is discussed where known. Analyses of DNA sequences of D2/D3 and COI suggested that the six new species are distributed between three clades of Fergusobia.
Pachybrachis holerorum (Coleoptera: Chrysomelidae: Cryptocephalinae), a new species from the Apennines, Italy, identified by integration of morphological and molecular data
Authors: MONTAGNA MATTEO , SASSI DAVIDE , GIORGI ANNAMARIA
Published: November 2013

Pachybrachis holerorum n. sp. is described from the northern Apennines, Italy. The new species is related to P. karamani (Weise, 1893), from which it differs in the shape of the median lobe of the aedeagus and in small differences in chromatic pattern. The close relationship with P. karamani is confirmed by molecular analyses performed on a fragment of 829 nucleotides of the mitochondrial gene Cytochrome c oxidase subunit 1 (cox1). The general mixed Yule-coalescent model, developed for species delimitation using single-locus molecular data, was applied to a cox1 phylogeny in order to test the hypothesis of P. holerorum as a separate species. Information on the host plants, acquired during specimen collection, was confirmed from gut content, targeting a fragment of the plastid large subunit of the ribulose-bisphosphate carboxylase gene and the trnL(UAA) intron. Besides, the lectotype of P. karamani is designated.
Nested Large-Eddy Simulations of the Intermittently Turbulent Stable Atmospheric Boundary Layer over Real Terrain
Authors: Zhou Bowen , Chow Fotini Katopodes
Published: November 2013

The nighttime stable atmospheric boundary layer over real terrain is modeled with nested high-resolution large-eddy simulations (LESs). The field site is located near Leon, Kansas, where the 1999 Cooperative Atmosphere–Surface Exchange Study took place. The terrain is mostly flat with an average slope of 0.5°. The main topographic feature is a shallow valley oriented in the east–west direction. The night of 5 October is selected to study intermittent turbulence under prevailing quiescent conditions. Brief turbulent periods triggered by shear-instability waves are modeled with good magnitude and temporal precision with a dynamic reconstruction turbulence closure. In comparison, conventional closures fail to excite turbulent motions and predict a false laminar flow. A plausible new intermittency mechanism, previously unknown owing to limited spatial coverage of field instruments at this site, is unveiled with the LESs. Turbulence can be generated through gravity wave breaking over a stagnant cold-air bubble in the valley upwind of the main tower. The bubble is preceded by the formation of a valley cold-air pool due to down-valley drainage flows during the evening transition. The bubble grows in depth by entraining cold down-valley and downslope flows from below and is eroded by shear-induced wave breaking on the top. The cyclic process of formation and erosion is repeated during the night, leading to sporadic turbulent bursting.
High-Resolution Hurricane Vector Winds from C-Band Dual-Polarization SAR Observations
Authors: Zhang Biao , Perrie William , Zhang Jun A. , Uhlhorn Eric W. , He Yijun
Published: November 2013

This study presents a new approach for retrieving hurricane surface wind vectors utilizing C-band dual-polarization (VV, VH) synthetic aperture radar (SAR) observations. The copolarized geophysical model function [C-band model 5.N (CMOD5.N)] and a new cross-polarized wind speed retrieval model for dual polarization [C-band cross-polarized ocean surface wind retrieval model for dual-polarization SAR (C-2POD)] are employed to construct a cost function. Minimization of the cost function allows optimum estimates for the wind speeds and directions. The wind direction ambiguities are removed using a parametric two-dimensional sea surface inflow angle model. To evaluate the accuracy of the proposed method, two RADARSAT-2 SAR images of Hurricanes Bill and Bertha are analyzed. The retrieved wind speeds and directions are compared with collocated Quick Scatterometer (QuikSCAT) winds, showing good consistency. Results suggest that the proposed method has good potential to retrieve hurricane surface wind vectors from dual-polarization SAR observations.
Extended-Range Forecasts of Atlantic Tropical Cyclone Events during 2012 Using the ECMWF 32-Day Ensemble Predictions*
Authors: Elsberry Russell L. , Tsai Hsiao-Chung , Jordan Mary S.
Published: November 2013

Previous studies have demonstrated the capability of the European Centre for Medium-Range Weather Forecasts (ECMWF) 51-member, 32-day ensemble to forecast tropical cyclone (TC) events (formation and tracks) in the western North Pacific on the extended range (5–30 days). In this study, the performance of the ECMWF ensemble in extended-range forecasting of Atlantic TCs during May–December 2012 is evaluated using similar approaches. The conclusion from this evaluation is that Atlantic TC events have lower forecastability using the ECMWF ensemble than in the western North Pacific. Hurricanes Kirk and Leslie and Tropical Storms (TSs) Joyce and Oscar were successfully forecast in weeks 1–4 and, thus, are labeled as highly forecastable. Somewhat forecastable storms that are only forecast in three of the four weeks include Hurricanes Ernesto, Isaac, Nadine, and Sandy plus TS Florence. The limited forecastable storms that were successful in only the first two weeks include Hurricanes Gordon and Rafael plus TS Debby. The surprising result was that two hurricanes (Chris and Michael) and three TSs (Helene, Patty, and Tony) were not even forecast in week 1 before the starting time in the National Hurricane Center working best track (WBT) for these storms. As was the case in the western North Pacific, a substantial number of false alarm storms (no matches with any WBT) are predicted, with about 35% occurring in the first week. Except for the African wave–type false alarms, three other false alarm types may be easily recognized. A larger sample will be required to statistically verify the reliability of the probabilistic forecasts for the African wave–type ensemble storms.
Association Between In-Hospital Mortality and Renal Dysfunction in 186 219 Patients Hospitalized for Acute Stroke in the Emilia-Romagna Region of Italy
Authors: Fabbian Fabio , Gallerani Massimo , Pala Marco , De Giorgi Alfredo , Salmi Raffaella , Dentali Francesco , Ageno Walter , Manfredini Roberto
Published: November 2013

Using a regional Italian database, we evaluated the relationship between renal dysfunction and in-hospital mortality (IHM) in patients with acute stroke (ischemic/hemorrhagic). Patients were classified on the basis of renal damage: without renal dysfunction, with chronic kidney disease (CKD), and with end-stage renal disease (ESRD). Of a total of 186 219 patients with a first episode of stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total cases) was independently associated with CKD, ESRD, atrial fibrillation (AF), age, and Charlson comorbidity index (CCI). In patients with ischemic stroke (n = 154 026), IHM remained independently associated with CKD, ESRD, AF, and CCI. In patients with hemorrhagic stroke (n = 32 189), variables that were independently associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with IHM related to stroke, both ischemic and hemorrhagic, with even higher odds ratios than those of other established risk factors, such as age, comorbidities, and AF.
Markers of Endothelial Dysfunction and Evaluation of Vascular Reactivity Tests in Behçet Disease
Authors: Ozuguz Pinar , Karabulut Ayse Anil , Tulmac Murat , Kisa Ucler , Kocak Mukadder , Gunduz Ozgur
Published: November 2013

We assessed endothelial dysfunction (ED) in patients with Behcet disease (BD; n = 40) and healthy controls (n = 20). Serum lipid, homocysteine, asymmetric dimethylarginine (ADMA) and high-sensitivity C-reactive protein (hsCRP) levels, erythrocyte sedimentation rates (ESRs), and ultrasonographic flow-mediated dilatation (FMD) were measured. Mean hsCRP, ESR, homocysteine, and ADMA were significantly higher in the BD group ( P < .001 for all). Patients with active BD had higher serum levels of hsCRP, homocysteine, and ESR compared with those in remission ( P < .001, P < .001, and P = .005, respectively). Flow-mediated dilatation was significantly lower in patients with BD than in controls ( P = .001). Flow-mediated dilatation correlated negatively with BD duration and serum ADMA levels ( P < .001, r = −.745 and P < .001, r = −.682); a positive correlation was seen between serum ADMA levels and BD duration ( P < .001, r = .552). Only stepwise multivariate regression analysis revealed BD duration to have a significant effect on FMD. Flow-mediated dilatation, in conjunction with markers of inflammation, may evaluate ED in patients with BD.
Testing the Reciprocal Relationship between Attitudes and Land Use in Relation to Trip Frequencies
Authors: Gim Tae-Hyoung Tommy
Published: November 2013

Nonrecursive structural equation modeling is applied to cross-sectional data from a survey conducted in Seoul, Korea, in 2009 and from geographic information systems, in an effort to model the reciprocal relationship between attitudes toward travel modes and land use in a neighborhood. Then, this study examines how the direction of the relationship differentiates the effects that the two factors have on trip frequencies. The direction is found to be contingent on trip purpose, that is, the attitudes–land use relationship is recursive for commuting trips, reciprocal for leisure trips, and insignificant for shopping trips. If the attitudes are omitted altogether, the estimated land use effect decreases considerably for commuting trips and slightly for leisure trips, which suggests the degree to which residential self-selection is concerned with these purposes of trips.
Boko Haram, Religious Violence, and the Crisis of National Identity in Nigeria
Authors: Agbiboa Daniel Egiegba , Maiangwa Benjamin
Published: November 2013

Since Nigeria’s return to democratic rule in 1999, more than 10,000 people have died in the wake of identity-based violence mostly fought along ethno-religious lines. In 2009, a radical Islamist sect from north-eastern Nigeria, Boko Haram, started a campaign of terror that has so far intensified the apprehensive religious atmosphere in the country. While the Boko Haram crisis cannot be said to be strictly religious, this article will locate the group within the context of the mobilization and politicization of religion in Nigeria, which along with the heavy-handedness of Nigeria’s conflict management processes, informs religious militancy and sectarian violence in the country. We argue that a process of transition from a killing society to a non-killing society is needed to provide an alternative perspective to the existing pedagogy of violence for which northern Nigeria is notorious.
Community Rights, Individual Rights, and Toleration
Authors: Amtaika Alexius
Published: November 2013

The conviction of a gay couple in Malawi on May 20, 2010 raises serious questions about issues of cultural rights, individual rights, community rights, and the rule of law. Individuals live in communities and are bound by the norms, rules, and regulations of their customs, traditions, and culture. In terms of natural rights, however, individuals have the freedom of choice to live as they please, as long as their actions do not infringe on the rights of others. The problem arises when community rights clash with individual rights, and the community denies individuals the exercise of their freedom of choice. The handing down of a 14-year prison sentence, with hard labor, by a Magistrate’s Court to a gay couple convicted for gross public indecency in the Republic of Malawi is a case in point. This sentence not only contravenes the rights of the individual in terms of natural justice but also violates the Constitution of Malawi which outlaws discrimination of any kind and advocates equality. This article maintains that coexistence and harmony among individuals in plural societies can be achieved only through tolerance, which is an essential condition for liberty and democracy.
Kinematic and dynamic modeling of spherical joints using exponential coordinates
Authors: Kim Jinwook , Lee Sung-Hee , Park Frank C
Published: November 2013

Traditional Euler angle-based methods for the kinematic and dynamic modeling of spherical joints involve highly complicated formulas that are numerically sensitive, with complex bookkeeping near local coordinate singularities. In this regard, exponential coordinates are known to possess several advantages over Euler angle representations. This paper presents several new exponential coordinate-based formulas and computational procedures that are particularly useful in the modeling of mechanisms containing spherical joints. Computationally robust procedures are derived for evaluating the forward and inverse formulas for the angular velocity and angular acceleration in terms of exponential coordinates. We show that these formulas simplify the parametrization of joint range limits for spherical joints, and lead to more compact equations in the forward and inverse dynamic analysis of mechanisms containing spherical joints.
Parallel singularity-free design with actuation redundancy: A case study of three different types of 3-degree-of-freedom parallel mechanisms with redundant actuation
Authors: Shin Kyoosik , Yi Byung-Ju , Kim Wheekuk
Published: November 2013

Typical parallel mechanisms suffer from parallel singularity due to kinematic coupling of multichains. This paper investigates how to remove parallel singularities by using redundant actuations. First, actuation wrenches and constraint wrenches forming the full direct kinematic Jacobian matrix are derived. After briefly addressing conditions for their constraint singularities, Grassmann–Cayley algebra is employed to identify parallel singularities. Then, employing Grassmann line geometry, the locations and the minimum number of redundant actuators are identified for the parallel mechanisms to have parallel singularity-free workspace. Three different types of 3-degree-of-freedom parallel mechanisms such as planar, spherical, and spatial parallel mechanisms are given as exemplary devices.
Party loyalty and electoral dealignment
Authors: André Audrey , Depauw Sam , Beyens Stefanie
Published: November 2013

Representative democracy is party democracy. Parties vote together in the legislative arena; party labels act as information shortcuts in the electoral arena, tying together co-partisan legislators’ re-election prospects. But the utility of party labels is weakened by waning party identifications in the electorate. Partisan dealignment therefore risks undercutting party loyalty on the part of backbenchers. Combining district-level data on electoral volatility and new data from the PARTIREP survey of legislators in 15 advanced industrial democracies, it is demonstrated that party loyalty is lowest where partisan dealignment is strongest – even after accounting for backbenchers’ policy preferences, whether they represent the ruling party or the opposition, and their campaign strategies. Our results have important implications for the sustainability of current models of representative democracy.
The Mediating Role of Perceptions of Abusive Supervision in the Relationship Between Personality and Aggression
Authors: Brees Jeremy , Mackey Jeremy , Martinko Mark , Harvey Paul
Published: November 2013

This study examines whether subordinates’ perceptions of abusive supervision mediate the relationship between subordinate personality and aggression. Results from a cross-organizational sample of 411 working adults suggest that subordinates’ perceptions of abusive supervision account for some of the variance in the relationships between subordinate Agreeableness, Emotional Stability, Extraversion, and subordinate aggression. This study suggests that social-information processing and perceptions of control found within subordinates’ personality influences whether they are more or less likely to perceive supervisory abuse. Perceptions of supervisory abuse were associated with aggression.
A Spontaneously Ruptured Hepatic Metastasis From a Gastric Gastrointestinal Stromal Tumor That Presented as Hemoperitoneum
Authors: Yoon Jung-Hee
Published: November 2013

Spontaneous hepatic hemorrhage is a rare condition that may be caused by an underlying hepatic tumor, most commonly hepatocellular carcinoma or hepatic adenoma. A spontaneous rupture of a hepatic metastasis from a gastric gastrointestinal stromal tumor is also extremely rare, and the majority of affected patients present with hypovolemic shock or an acute abdomen. In this article, we report the case of a 65-year-old man with a spontaneous rupture of a hepatic metastasis from a gastric gastrointestinal stromal tumor that presented as hypovolemic shock. Cross-sectional imaging studies (computed tomography or magnetic resonance imaging) play a significant role in the diagnosis of this condition and guides its management.
Surface characteristics and fatigue performance of warm shot peened wrought magnesium alloy Mg–9Gd–2Y
Authors: Huang Y. , Liu W. C. , Dong J.
Published: November 2013

The surface characteristics and fatigue performance of the warm shot peened Mg–9Gd–2Y alloys were investigated. Compared to conventional shot peening (SP) at room temperature, warm shot peening (WSP) at 240°C induces higher subsurface hardening and larger maximum compressive residual stress in the subsurface of the specimens. The optimum Almen intensity of WSP is 0·15 mm N, whereas it is 0·10 mm N for SP. The main reason is that the surface of warm shot peened specimen is more plastically deformed but less damaged at the optimum Almen intensity due to the increase in plastic deformation ability of the tested alloys at elevated temperature. The fatigue strength of the tested alloy at 107 cycles is increased from 125 to 175 MPa by optimum SP and to 185 MPa by optimum WSP.
MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia cells
Authors: Liu Suiyang , Yin Li , Stroopinsky Dina , Rajabi Hasan , Puissant Alexandre , Stegmaier Kimberly , Avigan David , Kharbanda Surender , Kufe Donald , Stone Richard
Published: November 2013

Key Points

The MUC1-C oncoprotein is aberrantly expressed in AML cells and contributes to activation of the mutant FLT3 receptor. Targeting MUC1-C thus inhibits FLT3 signaling and represents a potential approach for AML cells resistant to FLT3 inhibitors.
BORIS/CTCFL is an RNA-binding protein that associates with polysomes
Authors: Ogunkolade Babatunji W , Jones Tania A , Aarum Johan , Szary Jaroslaw , Owen Nicholas , Ottaviani Diego , Mumin Muhammad A , Patel Shyam , Pieri Christopher A , Silver Andrew R , Sheer Denise
Published: November 2013

Background

BORIS (CTCFL), a paralogue of the multifunctional and ubiquitously expressed transcription factor CTCF, is best known for its role in transcriptional regulation. In the nucleus, BORIS is particularly enriched in the nucleolus, a crucial compartment for ribosomal RNA and RNA metabolism. However, little is known about cytoplasmic BORIS, which represents the major pool of BORIS protein.

Results

We show, firstly, that BORIS has a putative nuclear export signal in the C-terminal domain. Furthermore, BORIS associates with mRNA in both neural stem cells and young neurons. The majority of the BORIS-associated transcripts are different in the two cell types. Finally, by using polysome profiling we show that BORIS is associated with actively translating ribosomes.

Conclusion

We have demonstrated the RNA binding properties of cellular BORIS and its association with actively translating ribosomes. We suggest that BORIS is involved in gene expression at both the transcriptional and post-transcriptional levels.
Iterative feature removal yields highly discriminative pathways
Authors: O’Hara Stephen , Wang Kun , Slayden Richard A , Schenkel Alan R , Huber Greg , O’Hern Corey S , Shattuck Mark D , Kirby Michael
Published: November 2013

Background

We introduce Iterative Feature Removal (IFR) as an unbiased approach for selecting features with diagnostic capacity from large data sets. The algorithm is based on recently developed tools in machine learning that are driven by sparse feature selection goals. When applied to genomic data, our method is designed to identify genes that can provide deeper insight into complex interactions while remaining directly connected to diagnostic utility. We contrast this approach with the search for a minimal best set of discriminative genes, which can provide only an incomplete picture of the biological complexity.

Results

Microarray data sets typically contain far more features (genes) than samples. For this type of data, we demonstrate that there are many equivalently-predictive subsets of genes. We iteratively train a classifier using features identified via a sparse support vector machine. At each iteration, we remove all the features that were previously selected. We found that we could iterate many times before a sustained drop in accuracy occurs, with each iteration removing approximately 30 genes from consideration. The classification accuracy on test data remains essentially flat even as hundreds of top-genes are removed.

Our method identifies sets of genes that are highly predictive, even when comprised of genes that individually are not. Through automated and manual analysis of the selected genes, we demonstrate that the selected features expose relevant pathways that other approaches would have missed.

Conclusions

Our results challenge the paradigm of using feature selection techniques to design parsimonious classifiers from microarray and similar high-dimensional, small-sample-size data sets. The fact that there are many subsets of genes that work equally well to classify the data provides a strong counter-result to the notion that there is a small number of “top genes” that should be used to build classifiers. In our results, the best classifiers were formed using genes with limited univariate power, thus illustrating that deeper mining of features using multivariate techniques is important.
A transcriptomic approach to elucidate the physiological significance of human cytochrome P450 2S1 in bronchial epithelial cells
Authors: Madanayake Thushara W , Lindquist Ingrid E , Devitt Nicholas P , Mudge Joann , Rowland Aaron M
Published: November 2013

Background

Cytochrome P450 2S1 (CYP2S1) is an orphan P450 with an unknown biological function. Data from our laboratory and others suggest that CYP2S1 may have an important physiological role in modulating the synthesis and metabolism of bioactive lipids including prostaglandins and retinoids. CYP2S1 expression is elevated in multiple epithelial-derived cancers as well as in the chronic hyperproliferative disease psoriasis. Whether CYP2S1 expression in proliferative disease is protective, detrimental, or neutral to disease progression remains to be determined. Two human bronchial epithelial cells (BEAS-2B) were constructed to represent chronic depletion of CYP2S1 using short-hairpin RNA (shRNA) silencing directed toward the 3’UTR (759) and exon 3 (984) of the CYP2S1 gene and compared with a non-targeting shRNA control (SCRAM). Both CYP2S1 mRNA and protein were depleted by approximately 75% in stable cell lines derived from both targeted shRNA constructs (759 and 984). To elucidate the biological significance of CYP2S1, we analyzed transcriptome alterations in response to CYP2S1 depletion in human lung cells.

Results

RNA-sequencing (RNA-seq) analysis was performed to compare the transcriptome of the control (SCRAM) and the CYP2S1-depleted (759) BEAS-2B cell lines. Transcriptomes of the replicates from the two cell lines were found to be distinct populations as determined using Principal Component Analysis and hierarchical clustering. Approximately 1000 genes were differentially expressed in response to CYP2S1 depletion. Consistent with our previous phenotypes, DAVID analysis revealed altered regulation in key pathways implicated in cell proliferation and migration. Transcriptomic profiles were also consistent with the metabolism of proposed endogenous substrates. Pathway analysis also revealed significant expression changes within mTOR signaling, a critical pathway in cell growth. To determine whether these changes manifest as altered cell size, cell diameter and volume were calculated, revealing that CYP2S1 depletion promotes cell growth in BEAS-2B cells.

Conclusions

These data suggest that pathway analysis of sequence-based gene expression is a powerful method to identify pathways and phenotypic alterations in response to changes in orphan enzyme expression. Our results suggest a novel role for CYP2S1-mediated metabolism in modulating BEAS-2B cell size. These findings warrant further studies on CYP2S1 regulated pathways to elucidate potential substrates of CYP2S1.
Challenges in diagnostic accuracy studies in primary care: the fecal calprotectin example
Authors: Holtman Gea A , Yvonne Lisman-van Leeuwen , Kollen Boudewijn J , Escher Johanna C , Kindermann Angelika , Patrick F van Rheenen , Berger Marjolein Y
Published: November 2013

Background

Low disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of our choices, using a quality assessment tool for diagnostic accuracy studies (QUADAS-2).

Design

The study investigates the diagnostic value of fecal calprotectin for detecting inflammatory bowel disease in children presenting with chronic gastrointestinal symptoms in primary care. It is a prospective cohort study including two cohorts of children: one cohort will be recruited in primary care and the other in secondary/tertiary care. Test results of fecal calprotectin will be compared to one of the two reference standards for inflammatory bowel disease: endoscopy with histopathological examination of mucosal biopsies or assessment of clinical symptoms at 1-year follow-up.

Discussion

According to QUADAS-2 the use of two reference standards and the recruitment of patients in two populations may cause differential verification bias and spectrum bias, respectively. The clinical relevance of this potential bias and methods to adjust for this are presented. This study illustrates the importance of awareness of the different kinds of bias that result from choices in the design phase of a diagnostic study in a low prevalence setting. This approach is exemplary for other diagnostic research in primary care.
National trends in advanced outpatient diagnostic imaging utilization: an analysis of the medical expenditure panel survey, 2000-2009
Authors: Lang Kathleen , Huang Huan , Lee David W , Federico Victoria , Menzin Joseph
Published: November 2013

Background

Concerns have been raised regarding growth in advanced diagnostic imaging use. This study evaluated trends in national outpatient MRI/CT utilization rates during 2000-2009 and factors associated with utilization.

Methods

This retrospective database analysis used data on all respondents in the nationally representative U.S. Medical Expenditure Panel Survey (MEPS) during 2000-2009. Visits involving advanced diagnostic imaging were identified based on self-reported use of MRI or CT tests at emergency departments, office-based medical providers, and outpatient departments. The imaging utilization rate was defined as the number of outpatient visits with MRI/CT per 1,000 person-years. Results were weighted to create nationally representative estimates at the person-year level for each year and the pooled 10-year period. A multivariate logistic regression was estimated to identify predictors of imaging use.

Results

A total of 319,246 person-years were included in the analysis. MRI/CT utilization rates increased from 64.3 to 109.1 per 1,000 person years from 2000 to 2009, with older persons, females and Medicare enrollees having higher rates of use. Growth in imaging slowed in recent years; the average annual decline in the imaging growth rate was larger than that for all outpatient services (4.7% vs. 0.9%). The percentage of respondents with MRI/CT use (6.7% during 2000-2009) also increased at a slower rate in later years and declined during 2007-2009. The average number of MRI/CT visits among imaging users was steady at about 1.5 visits during 2000-2009. Age, female gender, White race, HMO participation, and all payer types (vs. uninsured) were significant predictors of imaging use. Compared to 2005, years 2000-2003 were associated with a significantly lower likelihood of imaging use, while years 2004-2009 were not significantly associated, suggesting a slow-down in later years.

Conclusions

Growth in advanced imaging utilization appears to have slowed in recent years, a finding of potential interest to policy-makers and payers.
Aqueous extracts of Liriope platyphylla induced significant laxative effects on loperamide-induced constipation of SD rats
Authors: Kim Ji Eun , Lee Young Ju , Kwak Moon Hwa , Ko Jun , Hong Jin Tae , Hwang Dae Youn
Published: November 2013

Background

Liriope platyphylla has long been reported as a therapeutic drug for treatment of various human chronic diseases including inflammation, diabetes, neurodegenerative disorders, obesity, and atopic dermatitis. To investigate the laxative effects of L. platyphylla, alterations in excretion parameters, histological structure, mucin secretion, and related protein levels were investigated in rats with loperamide (Lop)-induced constipation after treatment with aqueous extract of L. platyphylla (AEtLP).

Methods

Alterations on constipation phenotypes were measured in rats with Lop-induced constipation after treatment with AEtLP using excretion parameter analysis, histological analysis, RT-PCR, western blot and transmission electron microscope (TEM) analysis.

Results

The amounts of stool and urine excretion were significantly higher in the Lop + AEtLP-treated group than in the Lop + vehicle-treated group, whereas food intake and water consumption were maintained at constant levels. AEtLP treatment also induced an increase in villus length, crypt layer, and muscle thickness in the constipation model. Total mucin secretion was higher in the Lop + AEtLP-treated group than in the Lop + vehicle-treated group, although mucin secretion per crypt was very similar among all groups. Furthermore, RT-PCR and western blot revealed a dramatic reduction of key factors level on the muscarinic acetylcholine receptors (mAChRs) signaling pathway in the Lop + AEtLP-treated group relative to the Lop + vehicle-treated group. Especially, the accumulation of lipid droplets in enterocytes of crypts following Lop treatment was improved to the level of the No-treated group in response to AEtLP treatment.

Conclusion

These results suggest that AEtLP improves constipation induced by Lop treatment through an increase in crypt layer and stimulation of lipid droplet secretions. These data are the first to show that the laxative effects of AEtLP are closely related to the down-regulation of mAchRs and their downstream signals.
Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat
Authors: Lee Ki Mo , Bang Ji Hye , Han Jung-Soo , Kim Bu Yeo , Lee In Sun , Kang Hyung Won , Jeon Won Kyung
Published: November 2013

Background

The cardiotonic pill (CP) is a herbal medicine composed ofSalvia miltiorrhiza(SM),Panax notoginseng(PN), andDryobalanops aromatica Gaertner(DAG) that is widely used to treat cardiovascular diseases. The present experiment was conducted to examine the effects of CP on white matter and hippocampal damage induced by chronic cerebral hypoperfusion.

Methods

Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). Daily oral administration of CP (200 mg/kg) began 21 days after BCCAo and continued for 42 days. The levels of microglial activation and myelin basic protein (MBP) were measured in the white matter and hippocampus of rats with chronic BCCAo, and the expression levels of mitogen-activated protein kinases (MAPKs) and inflammatory markers such as cyclooxygenase-2, interleukin-1β, and interleukin-6 were examined.

Results

MBP expression was reduced in the white matter and hippocampal regions of rats that received BCCAo. In contrast, reduced levels of MBP were not observed in BCCAo rats given CP treatments. The administration of CP alleviated microglial activation, the alteration of ERK and p38 MAPK signaling, and inflammatory mediator expression in rats with chronic BCCAo.

Conclusion

These results suggest that CP may have protective effects against chronic BCCAo-induced white matter and hippocampal damage by inhibiting inflammatory processes including microglial activation and proinflammatory mediator expression, and downreguating the hyperphosphorylation of ERK and p38 MAPK signaling.
Should level V be included in lateral neck dissection in treating papillary thyroid carcinoma?
Authors: Zhang Xiao-Jun , Liu Dan , Xu De-Bin , Mu Ya-Qi , Chen Wen-Kuan
Published: November 2013

Background

The study was designed to explore the regular patterns of level V lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC), and to indicate whether level V should be included in the management of lateral neck dissection when treating PTC.

Methods

This retrospective study consisted of 330 patients diagnosed with PTC from January 1994 to July 2009 who underwent an operation that included therapeutic lateral neck dissection (levels II to V). The patterns of lateral neck LNM were analyzed and the relevant risk factors of level V LNM were analyzed with univariate and multivariate analysis, respectively.

Results

All the patients underwent lateral neck dissection at levels II to V. The predominant site of metastasis was level III (247/330 (74.8%)), followed by level IV (233/330 (70.6%)), and level II (215/330 (65.3%)). Simultaneous multilevel involvement (level II, III, and IV) of lymphatic metastases presented in 46.1% (152/330) of the cases. Level V showed 28.8% (95/330) of nodal metastasis. Multivariate analysis showed that level V LNM was significantly associated with location (whole thyroid), gross extrathyroidal extension and simultaneous multilevel involvement (level II, III and IV). (P <0.05).

Conclusions

Due to relatively high rate of level V involvement and its correlation with location (whole thyroid), gross extrathyroidal extension and multilevel involvement, we consider that it may be more rational to include level V in the therapeutic lateral neck dissection when treating PTC, especially for those who have any one of these three independent risk factors.