bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropometric measurements of general and central obesity and the prediction of cardiovascular disease risk in women: a cross-sectional study
Authors: Goh Louise G H , Dhaliwal Satvinder S , Welborn Timothy A , Lee Andy H , Della Phillip R
Published: February 2014

Objectives

It is important to ascertain which anthropometric measurements of obesity, general or central, are better predictors of cardiovascular disease (CVD) risk in women. 10-year CVD risk was calculated from the Framingham risk score model, SCORE risk chart for high-risk regions, general CVD and simplified general CVD risk score models. Increase in CVD risk associated with 1 SD increment in each anthropometric measurement above the mean was calculated, and the diagnostic utility of obesity measures in identifying participants with increased likelihood of being above the treatment threshold was assessed.

Design

Cross-sectional data from the National Heart Foundation Risk Factor Prevalence Study.

Setting

Population-based survey in Australia.

Participants

4487 women aged 20–69 years without heart disease, diabetes or stroke.

Outcome measures

Anthropometric obesity measures that demonstrated the greatest increase in CVD risk as a result of incremental change, 1 SD above the mean, and obesity measures that had the greatest diagnostic utility in identifying participants above the respective treatment thresholds of various risk score models.

Results

Waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-stature ratio had larger effects on increased CVD risk compared with body mass index (BMI). These central obesity measures also had higher sensitivity and specificity in identifying women above and below the 20% treatment threshold than BMI. Central obesity measures also recorded better correlations with CVD risk compared with general obesity measures. WC and WHR were found to be significant and independent predictors of CVD risk, as indicated by the high area under the receiver operating characteristic curves (>0.76), after controlling for BMI in the simplified general CVD risk score model.

Conclusions

Central obesity measures are better predictors of CVD risk compared with general obesity measures in women. It is equally important to maintain a healthy weight and to prevent central obesity concurrently.
The case of the whelping bitch
Authors: McCulloch Steven
Published: February 2014

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.

In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘The case of the whelping bitch’, was submitted and is discussed by Steven McCulloch. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Dealing with dark desires’, which was published in the January issue of In Practice, appears on page 103.

The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Paediatric emergency and critical care 1. General principles
Authors: Serrano Sergi
Published: February 2014

Dealing with very young dogs and cats in an emergency room or intensive care unit represents a true challenge, due to their uniquely changing nature and the differences compared with adult patients. The lack of maturation and appropriate function for many of the homeostatic and compensatory mechanisms in these patients warrants very thorough monitoring and precise tailoring of any therapy, while their impressive ability to recover makes treating them a highly rewarding experience. This article, the first in a two‐part series, will address the normal findings in paediatric patients and the general principles of emergency medicine and critical care for this population. A second article, to be published in a future issue of In Practice, will focus on how to deal with specific conditions that are particularly frequent in puppies and kittens.
Radiative rates for E1, E2, M1, and M2 transitions among the 3s23p5, 3s3p6, and 3s23p43d configurations of Cl-like W LVIII
Authors: Aggarwal Kanti M. , Keenan Francis P.
Published: February 2014

We report calculations of energy levels, radiative decay rates, and lifetimes for transitions among the 3s23p5, 3s3p6, and 3s23p43d configurations of Cl-like W LVIII. The general-purpose relativistic atomic structure package (GRASP) has been adopted for our calculations. Comparisons are made with the most recent results of Mohan et al. (Can. J. Phys. 92, 177 (2014). doi:10.1139/cjp-2013-0348) and discrepancies in lifetimes are noted, up to four orders of magnitude in some instances. Our energy levels are estimated to be accurate to better than 0.5%, whereas results for radiative rates and lifetimes should be accurate to better than 20%.
AN UNSUPERVISED COLOR-TEXTURE SEGMENTATION USING TWO-STAGE FUZZY c-MEANS ALGORITHM
Authors: XU SHAOPING , HU LINGYAN , LI CHUNQUAN , YANG XIAOHUI , LIU XIAOPING P.
Published: February 2014

Unsupervised image segmentation is a fundamental but challenging problem in computer vision. In this paper, we propose a novel unsupervised segmentation algorithm, which could find diverse applications in pattern recognition, particularly in computer vision. The algorithm, named Two-stage Fuzzy c-means Hybrid Approach (TFHA), adaptively clusters image pixels according to their multichannel Gabor responses taken at multiple scales and orientations. In the first stage, the fuzzy c-means (FCM) algorithm is applied for intelligent estimation of centroid number and initialization of cluster centroids, which endows the novel segmentation algorithm with adaptivity. To improve the efficiency of the algorithm, we utilize the Gray Level Co-occurrence Matrix (GLCM) feature extracted at the hyperpixel level instead of the pixel level to estimate centroid number and hyperpixel-cluster memberships, which are used as initialization parameters of the following main clustering stage to reduce the computational cost while keeping the segmentation performance in terms of accuracy close to original one. Then, in the second stage, the FCM algorithm is utilized again at the pixel level to improve the compactness of the clusters forming final homogeneous regions. To examine the performance of the proposed algorithm, extensive experiments were conducted and experimental results show that the proposed algorithm has a very effective segmentation results and computational behavior, decreases the execution time and increases the quality of segmentation results, compared with the state-of-the-art segmentation methods recently proposed in the literature.
ON THE FLAT BRAIDZEL LENGTH OF LINKS
Authors: MIURA TAKAHIRO
Published: February 2014

Any link has a flat braidzel presentation. We introduce a new integral invariant of links, named the flat braidzel length, with respect to the flat braidzel presentation. We give a lower bound for the flat braidzel length, and determine the flat braidzel length of an infinite family of links. Moreover, we give the table of knots with the flat braidzel length five or less.
Improved combination of RPCA and MEL for sparse representation-based face recognition
Authors: Khaji Rokan , Li Hong , Li Hongfeng , Haruna Rabiu , Alsaidi Ramadhan Abdo Musleh
Published: February 2014

Face recognition (FR) is an important and challenging task in pattern recognition and has many important practical applications. This paper presents an improved technique for Face Recognition, which consists of two phases where in each phase; a technique is employed effectively that is used extensively in computer vision and pattern recognition. Initially, the Robust Principal Component Analysis (RPCA) is used specifically in the first phase, which is employed to reduce dimensionality and to extract abstract features of faces. The framework of the second phase is sparse representation based classification (SRC) and introduced metaface learning (MFL) of face images. Experiments for face recognition have been performed on ORL and AR face database. It is shown that the proposed method can perform much best than other methods. And with the proposed method, we can obtain a best understanding of data.
Continuous quaternion fourier and wavelet transforms
Authors: Bahri Mawardi , Ashino Ryuichi , Vaillancourt Rémi
Published: February 2014

A two-dimensional (2D) quaternion Fourier transform (QFT) defined with the kernel [Formula: see text] is proposed. Some fundamental properties, such as convolution, Plancherel and vector differential theorems, are established. The heat equation in quaternion algebra is presented as an example of the application of the QFT to partial differential equations. The wavelet transform is extended to quaternion algebra using the kernel of the QFT.
Multistage blind source separations by wavelet analysis
Authors: Ashino Ryuichi , Mandai Takeshi , Morimoto Akira
Published: February 2014

The purpose of blind source separation is to separate the original sources from the sensor array, without knowing the transmission channel characteristics. Besides methods based on independent component analysis, several methods based on time-frequency analysis have been proposed. In this paper, a new method of multistage separation is proposed, which improves our formerly proposed methods using the time-scale information matrix based on the continuous multiwavelet transform.
Signal quantitative analysis using customizable perfect-translation-invariant complex wavelet functions
Authors: Toda Hiroshi , Zhang Zhong
Published: February 2014

In this paper, we introduce several methods of signal quantitative analysis using the perfect-translation-invariant complex wavelet functions (PTI complex wavelet functions), which are used in our proposed perfect-translation-invariant complex discrete wavelet transforms (PTI CDWTs) and can be designed by customization. First, using PTI complex wavelet functions, we define the continuous wavelet coefficient (CWC). Next, using orthonormal wavelet functions in the classical Hardy space, we analyze the CWC, and show that, using a CWC, we can measure the energy of a customizable frequency band, and additionally, using numbers of CWCs, we can measure the energy of the whole frequency band. Next, we introduce the fast calculation method of CWCs and show the applicability of the PTI CDWTs to digital signals. Based on them, we introduce some examples of signal quantitative analysis, including the methods to obtain instantaneous amplitude, instantaneous phase and instantaneous frequency. Additionally, we introduce the energy measurement of the whole frequency band using the PTI DT-CDWT, which is one of our proposed PTI CDWTs.
On the Fourier coefficients of meromorphic Jacobi forms
Authors: Olivetto René
Published: February 2014

In this paper, we describe the automorphic properties of the Fourier coefficients of meromorphic Jacobi forms. Extending results of Dabholkar, Murthy, and Zagier, and Bringmann and Folsom, we prove that the canonical Fourier coefficients of a meromorphic Jacobi form φ(z; τ) are the holomorphic parts of some (vector-valued) almost harmonic Maass forms. We also give a precise description of their completions, which turn out to be uniquely determined by the Laurent coefficients of φ at each pole, as well as some well-known real analytic functions, that appear for instance in the completion of Appell–Lerch sums.
Heavy mineral record of Andean uplift and changing sediment sources across the NE margin of South America: a case study from Trinidad and Barbados
Authors: Vincent Hasley , Wach Grant , Ketannah Yawooz
Published: February 2014

The heavy mineral compositions of sandstones in Trinidad and Barbados record the onset of Andean-related erosion and a reduction of craton-derived sediments into NE South America. The changing provenance was deduced by comparing heavy mineral assemblages interpreted from ancient sandstones with associations recognized in modern sands that can be reasonably correlated to existing tectonic domains. The impact of the Andean orogeny across the margin was to introduce a suite of minerals characteristic of low-temperature metamorphism that today is prevalent adjacent to the Caribbean Mountain belt and differs from the zircon-rich assemblage produced within cratonic plains. Twenty-one Paleocene–Late Pliocene sandstone samples from Trinidad revealed systematic changes in mineral diversity and maturity that recorded this provenance transition, and suggests Andean erosion during deposition of the Late Oligocene Nariva Formation. Similar to Palaeogene sandstones of Trinidad, four Eocene Scotland Formation samples from Barbados support craton derivation, but with additional evidence of minor Andean input probably due to the proximity of the Scotland Formation delivery systems to an earlier uplift episode. By the Late Miocene, most of the sediments delivered into Trinidad basins were supplied from the Andean orogeny as suggested by the relative abundance of minerals of this affinity. The heavy mineral records of Trinidad and Barbados are similar to that described across northern South America from both modern and ancient environments that collectively mark the uplift of the Andean mountain belt, with its strong influence on drainage patterns and reservoir provenance along this sector of the continental margin.

Supplementary material:

Sample location coordinates, sample and outcrop photographs, and summary outcrop sections are available at
http://www.geolsoc.org.uk/SUP18728
.
Physical characteristics of tephra layers in the deep sea realm: the Campanian Ignimbrite eruption
Authors: Engwell S. L. , Sparks R. S. J. , Carey S.
Published: February 2014

Tephra deposits in the deep sea can survive undisturbed for long periods of time and, on regional scales, tend to be much better preserved than their subaerial counterparts. In this study, grain size distributions and thicknesses of tephra deposits from the Campanian Ignimbrite (CI) eruption (39 000 yr BP; magnitude
c.
7.7) preserved in thirty-three deep sea cores are analysed to infer key eruption parameters. Distal deep sea tephra thickness data show an exponential decrease with distance from source. Such trends are difficult to identify in distal subaerial data owing to reworking and limited exposure. We find that tephra grain size distributions are much less affected by depositional environment than thickness, with trends that are consistent across distal subaerial, lacustrine and deep sea environments. The CI layer exhibits bimodal grain size distributions to distances of
c.
1000 km, after which it becomes unimodal. Such trends can be related to different mechanisms of tephra transport in the atmosphere, whereby at proximal to medial distances the Plinian and co-ignimbrite phases produce distinct plumes. Within 150 and 900 km from source, Plinian tephra constitutes 40±5% of the deposit volume. Beyond this region where coarse particles are deposited, the plumes merge and fines derived largely from co-ignimbrite elutriation are spread in the atmosphere at velocities greater than the settling velocities of the particles.
New insights into the Andean crustal structure between 32° and 34°S from GOCE satellite gravity data and EGM2008 model
Authors: Alvarez O. , Gimenez M. E. , Martinez M. P. , Lince Klinger F. , Braitenberg C.
Published: February 2014

The subduction of the Nazca oceanic plate under the South American plate in the south-central Andes region is characterized by the oblique collision of the Juan Fernandez Ridge against the continental margin. The upper plate is characterized by a broken foreland, a thrust-and-fold belt and eastward migration of the volcanic arc promoted by the flattening of the slab. Topographic load, thermal state and plate rheology determine the isostatic state of the continental plate. We calculated the vertical gravity gradient from GOCE satellite data in order to delineate the main tectonic features related to density variations resulting from internal and external loads. Then, using the Bouguer anomaly, we calculated the crust–mantle discontinuity and the elastic thickness in the frame of the isostatic lithospheric flexure model applying the convolution method approach. The results obtained show substantial variations in the structure of the continental lithosphere related to variations in the subduction angle of the Nazca plate. These variations are reflected in the varying Moho depths and in the plate rigidity, presenting a distinct behaviour in the southern zone, where the oceanic plate subducts with an approximate ‘normal’ angle with respect to the northern zone of the study area where the flat slab occurs.
Quaternary shortening at the orogenic front of the Central Andes of Argentina: the Las Peñas Thrust System
Authors: Costa Carlos H. , Ahumada Emilio A. , Gardini Carlos E. , Vázquez Fabricio R. , Diederix Hans
Published: February 2014

The NNW-trending Las Peñas Thrust System is one of the key structures along the Andean orogenic front between 32°15′ and 32°40′S in the Southern Precordillera of Argentina. This east-verging structure crops out over a distance of
c.
40 km and provides one of the best opportunities for a detailed field survey of Quaternary thrusting in the Andean frontal deformation zone. We present a systematic description of the geometry and geomorphic signatures of the main thrust deformation zone, which emplaces Neogene rocks over Quaternary alluvium, and usually behaves as a blind propagating thrust into the youngest (Late Pleistocene–Holocene) alluvial deposits. The Las Peñas Thrust System is understood to represent the latest stage of the eastward migration of an imbricated fan structure, which has driven the neotectonic uplift of the Las Peñas–Las Higueras range. Excellent outcrops provided by well-incised creek outlets reveal that the thrust system is made up either by a single fault surface or by two or more frontal splays. Several sections along its length can be differentiated on the basis of thrust geometries and/or morphotectonic features. The northern sections are characterized by isolated outcrops of Neogene rocks in the hanging wall, surrounded by alluvial bajadas. Remnants of fold limbs scarps depict the geomorphic signature of the thrust propagation into the Quaternary layers, although the preserved topographic relief always underestimates the cumulated thrust slip during the Quaternary. The southern part of this thrust system is defined by a frontal range, cored by a transposed south-plunging anticline in bedrock. Our observations suggest a dynamic and unsteady interaction between thrust propagation and sedimentation/erosion processes along the thrust trace during deposition of the Quaternary alluvial layers.
Characterizing the Paleocene turbidites of the North Sea: Maureen Formation, UK Central Graben
Authors: Kilhams Ben , Hartley Adrian , Huuse Mads , Davis Chris
Published: February 2014

This study presents an integrated seismic, well and core-based analysis of the Maureen Formation in the Central Graben of the North Sea. Facies analysis reveals that it is possible to divide the Maureen sandstones into amalgamated, sand- and mud-prone divisions, but that the related chalk facies are complex and imply a range of depositional processes including pelagic fallout, debris flows and turbidity currents. These chalk deposits have an impact on the interpretation of amplitude-based seismic attribute volumes. Detailed petrophysical mapping, supported by seismic analysis, reveals that the Maureen sandstones were deposited in distinct western and eastern fairways controlled by the relict Mesozoic rift topography (although offset stacking is an important intragraben process). The spatial extent of the Maureen sandstones is similar to the overlying Sele and Lista formations and suggests that the broad controls on sediment routing were the same throughout the Lower Palaeogene. Other similarities between these systems include the role of sandstone texture in controlling reservoir quality (although the heterolithic nature of the Maureen sandstones means that porosities and permeabilities are lower). A pattern of intraformational progradation and late-stage backstepping of the sandstone units is likely related to sea-level variability.
Depositional controls on fluid flow in the Gannet A Field
Authors: Lynn Gwilym J. , Bacciotti Morgan , Van Bergen Pim F. , Gray Kirsten R.
Published: February 2014

The Gannet A Field is an Eocene-aged Tay Sandstone Member reservoir located in the Central North Sea, with a thin oil rim and overlying gas cap that was developed in the early 1990s. The field comprises a very high quality reservoir and is connected to a large and active aquifer. These two factors in combination have led to a highly dynamic system during production, with significant migration of fluids around the field as offtake evolved. A considerable amount of surveillance data, including time-lapse (4D) seismic data, oil geochemical sampling and cased-hole saturation logs, has been acquired that allows the fluid flow and contact movement within the reservoir to be tracked. Integration of the individual datasets has allowed the key controls on fluid flow in the reservoir to be determined. The depositional architecture has strongly influenced reservoir behaviour, with the positioning and geometry of the non-net facies being the primary control on fluid flow, water-cut development and fluid distributions throughout the field. This has been demonstrated through static and dynamic reservoir modelling and validation of the results with the surveillance data.
Light on horizontal interactive surfaces
Authors: Bellucci Andrea , Malizia Alessio , Aedo Ignacio
Published: February 2014

In the last 25 years we have witnessed the rise and growth of interactive tabletop research, both in academic and in industrial settings. The rising demand for the digital support of human activities motivated the need to bring computational power to table surfaces. In this article, we review the state of the art of tabletop computing, highlighting core aspects that frame the input space of interactive tabletops: (a) developments in hardware technologies that have caused the proliferation of interactive horizontal surfaces and (b) issues related to new classes of interaction modalities (multitouch, tangible, and touchless). A classification is presented that aims to give a detailed view of the current development of this research area and define opportunities and challenges for novel touch- and gesture-based interactions between the human and the surrounding computational environment.
Distributed data management using MapReduce
Authors: Li Feng , Ooi Beng Chin , Özsu M. Tamer , Wu Sai
Published: February 2014

MapReduce is a framework for processing and managing large-scale datasets in a distributed cluster, which has been used for applications such as generating search indexes, document clustering, access log analysis, and various other forms of data analytics. MapReduce adopts a flexible computation model with a simple interface consisting of
map
and
reduce
functions whose implementations can be customized by application developers. Since its introduction, a substantial amount of research effort has been directed toward making it more usable and efficient for supporting database-centric operations. In this article, we aim to provide a comprehensive review of a wide range of proposals and systems that focusing fundamentally on the support of distributed data management and processing using the MapReduce framework.
A logarithmic approximation for unsplittable flow on line graphs
Authors: Bansal Nikhil , Friggstad Zachary , Khandekar Rohit , Salavatipour Mohammad R.
Published: February 2014

We consider the unsplittable flow problem on a line. In this problem, we are given a set of
n
tasks, each specified by a start time
s
i
, an end time
t
i
, a demand
d

i

> 0, and a profit
p

i

> 0. A task, if accepted, requires
d

i

units of “bandwidth” from time
s

i

to
t

i

and accrues a profit of
p

i

. For every time
t
, we are also specified the available bandwidth
c

t

, and the goal is to find a subset of tasks with maximum profit subject to the bandwidth constraints.

We present the first polynomial time
O
(log
n
) approximation algorithm for this problem. This significantly advances the state of the art, as no polynomial time
o
(
n
) approximation was known previously. Previous results for this problem were known only in more restrictive settings; in particular, either the instance satisfies the so-called “no-bottleneck” assumption: max

i

d

i

≤ min

t

c

t

, or the ratio of both maximum to minimum demands and maximum to minimum capacities are polynomially (or quasi-polynomially) bounded in
n
. Our result, on the other hand, does not require these assumptions.

Our algorithm is based on a combination of dynamic programming and rounding a natural linear programming relaxation for the problem. While there is an Ω(
n
) integrality gap known for this LP relaxation, our key idea is to exploit certain structural properties of the problem to show that instances that are bad for the LP can in fact be handled using dynamic programming.
Race to idle
Authors: Albers Susanne , Antoniadis Antonios
Published: February 2014

We study an energy conservation problem where a variable-speed processor is equipped with a sleep state. Executing jobs at high speeds and then setting the processor asleep is an approach that can lead to further energy savings compared to standard dynamic speed scaling. We consider classical deadline-based scheduling, that is, each job is specified by a release time, a deadline and a processing volume. For general convex power functions, Irani et al. [2007] devised an offline 2-approximation algorithm. Roughly speaking, the algorithm schedules jobs at a critical speed
s

crit

that yields the smallest energy consumption while jobs are processed. For power functions
P
(
s
) =
s
α
& γ, where
s
is the processor speed, Han et al. [2010] gave an α
α
+ 2)-competitive online algorithm.

We investigate the offline setting of speed scaling with a sleep state. First, we prove NP-hardness of the optimization problem. Additionally, we develop lower bounds, for general convex power functions: No algorithm that constructs
s

crit

-schedules, which execute jobs at speeds of at least
s

crit

, can achieve an approximation factor smaller than 2. Furthermore, no algorithm that minimizes the energy expended for processing jobs can attain an approximation ratio smaller than 2.

We then present an algorithmic framework for designing good approximation algorithms. For general convex power functions, we derive an approximation factor of 4/3. For power functions
P
(
s
) = β
s
α
+ γ, we obtain an approximation of 137/117 > 1.171. We finally show that our framework yields the best approximation guarantees for the class of
s

crit

-schedules. For general convex power functions, we give another 2-approximation algorithm. For functions
P
(
s
) = β
s
α
+ γ, we present tight upper and lower bounds on the best possible approximation factor. The ratio is exactly
eW
−1
(−
e

−1−1/
e

)/(
eW
−1
(−
e

−1−1/
e
)+1)

> 1.211, where
W
-1
is the lower branch of the Lambert
W
function.
Injection of autologous bone marrow cells in hyaluronan hydrogel improves cardiac performance after infarction in pigs
Authors: Chen Chien-Hsi , Chang Ming-Yao , Wang Shoei-Shen , Hsieh Patrick C. H.
Published: February 2014

Intramyocardial injection of bone marrow mononuclear cells (MNCs) with hyaluronan (HA) hydrogel is beneficial to the ischemic heart in a rat model of myocardial infarction (MI). However, the therapeutic efficacy and safety must be addressed in large animals before moving onto a clinical trial. Therefore, the effect of combined treatment on MI was investigated in pigs. Coronary artery ligation was performed in minipigs to induce MI followed by an intramyocardial injection of normal saline ( n = 7), HA ( n = 7), normal saline with 1 × 108 freshly isolated MNCs ( n = 8), or HA with 1 × 108 MNCs (HA-MNC; n = 7), with a sham-operated group serving as a control ( n = 7). The response of each experimental group was estimated by echocardiography, ventricular catheterization, and histological analysis. Although injection of HA or MNCs slightly elevated left ventricular ejection fraction, the combined HA-MNC injection showed a significant increase in left ventricular ejection fraction, contractility, infarct size, and neovascularization. Importantly, injection of MNCs with HA also promoted MNC retention and MNC differentiation into vascular lineage cells in pigs. Therefore, this study not only provides evidence but also raises the possibility of using a combined HA-MNC injection as a promising therapy for heart repair.
Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer
Authors: Beaver Julia A. , Jelovac Danijela , Balukrishna Sasidharan , Cochran Rory L. , Croessmann Sarah , Zabransky Daniel J. , Wong Hong Yuen , Valda Toro Patricia , Cidado Justin , Blair Brian G. , Chu David , Burns Timothy , Higgins Michaela J. , Stearns Vered , Jacobs Lisa , Habibi Mehran , Lange Julie , Hurley Paula J. , Lauring Josh , VanDenBerg Dustin A. , Kessler Jill , Jeter Stacie , Samuels Michael L. , Maar Dianna , Cope Leslie , Cimino-Mathews Ashley , Argani Pedram , Wolff Antonio C. , Park Ben Ho
Published: February 2014

Purpose: Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection.

Experimental Design: In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29). Tumors (n = 30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR.

Results: Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n = 29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery.

Conclusions: This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients. Clin Cancer Res; 20(10); 2643–50. ©2014 AACR.
Bone Marrow–Derived Mesenchymal Stromal Cells Promote Survival and Drug Resistance in Tumor Cells
Authors: Bergfeld Scott A. , Blavier Laurence , DeClerck Yves A.
Published: February 2014

Bone marrow mesenchymal stromal cells (BMMSC) have antitumorigenic activities. Here, we hypothesized that circulating BMMSC are incorporated into tumors and protect tumor cells from therapy-induced apoptosis. Adherent cells harvested from murine bone marrow and expressing phenotypic and functional characteristics of BMMSC were tested for their antitumor activity against murine 4T1 mammary adenocarcinoma and LL/2 Lewis lung carcinoma cells. BMMSC but not NIH3T3 or murine skin fibroblasts stimulated the expansion of 4T1 cells in three-dimensional (3D) cocultures, and conditioned medium (CM) from these cells increased the viability of 4T1 and LL/2 cells in two-dimensional (2D) cultures. 4T1 cells exposed to BMMSC CM exhibited a 2-fold reduction in apoptosis under low serum concentrations (0.5% to 1%). Furthermore, exposure of 4T1 and LL/2 cells to BMMSC CM increased their viability in the presence of paclitaxel or doxorubicin at therapeutic concentrations. This effect was accompanied by reductions in caspase-3 activity and Annexin V expression. When coinjected with 4T1 cells in the mammary fat pad of mice subsequently treated with doxorubicin, BMMSC (and not fibroblasts) also inhibited drug-induced apoptosis in tumor cells by 44%. We demonstrated that BMMSC were attracted by 4T1 and LL/2 cells but not by NIH3T3 cells in vitro and that when injected intravenously in 4T1 tumor-bearing mice, these cells (and not NIH3T3) were specifically detected in tumors within 12 to 18 days in which they preferentially localized at the invasive front. Overall, our data identify BMMSC as an important mediator of tumor cell survival and treatment resistance in primary tumors. Mol Cancer Ther; 13(4); 962–75. ©2014 AACR.
Novel Roles for ERK5 and Cofilin as Critical Mediators Linking ERα-Driven Transcription, Actin Reorganization, and Invasiveness in Breast Cancer
Authors: Madak-Erdogan Zeynep , Ventrella Rosa , Petry Luke , Katzenellenbogen Benita S.
Published: February 2014

Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. This study establishes an estrogen receptor (ERα)/MAPK (ERK5)/cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor–mediated transcription. Using dominant negative and constitutively active forms, as well as small-molecule inhibitors of extracellular signal–regulated kinase (ERK)5 and MAP–ERK kinase (MEK)5, it was revealed that hormone activation of ERα determined the subcellular localization of ERK5, which functions as a coregulator of ERα-dependent gene transcription. Notably, ERK5 acted in concert with the actin remodeling protein, CFL1, and upon hormone exposure, both localized to active nuclear transcriptional hubs as verified by immunofluorescence and proximity ligation assays. Both ERK5 and CFL1 facilitated PAF1 recruitment to the RNA Pol II complex and both were required for regulation of gene transcription. In contrast, in cells lacking ERα, ERK5 and CFL1 localized to cytoplasmic membrane regions of high actin remodeling, promoting cell motility and invasion, thereby revealing a mechanism likely contributing to the generally poorer prognosis of patients with ERα-negative breast cancer. Thus, this study uncovers the dynamic interplay of nuclear receptor–mediated transcription and actin reorganization in phenotypes of breast cancer aggressiveness.

Implications: Identification of the ER/ERK5/CFL1 axis suggests new prognostic biomarkers and novel therapeutic avenues to moderate cancer aggressiveness. Mol Cancer Res; 12(5); 714–27. ©2014 AACR.
Guidelines for the Prevention of Stroke in Women
Authors: Bushnell Cheryl , McCullough Louise D. , Awad Issam A. , Chireau Monique V. , Fedder Wende N. , Furie Karen L. , Howard Virginia J. , Lichtman Judith H. , Lisabeth Lynda D. , Piña Ileana L. , Reeves Mathew J. , Rexrode Kathryn M. , Saposnik Gustavo , Singh Vineeta , Towfighi Amytis , Vaccarino Viola , Walters Matthew R.
Published: February 2014

Purpose—

The aim of this statement is to summarize data on stroke risk factors that are unique to and more common in women than men and to expand on the data provided in prior stroke guidelines and cardiovascular prevention guidelines for women. This guideline focuses on the risk factors unique to women, such as reproductive factors, and those that are more common in women, including migraine with aura, obesity, metabolic syndrome, and atrial fibrillation.

Methods—

Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council’s Scientific Statement Oversight Committee and the AHA’s Manuscript Oversight Committee. The panel reviewed relevant articles on adults using computerized searches of the medical literature through May 15, 2013. The evidence is organized within the context of the AHA framework and is classified according to the joint AHA/American College of Cardiology and supplementary AHA Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive AHA internal peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee.

Results—

We provide current evidence, research gaps, and recommendations on risk of stroke related to preeclampsia, oral contraceptives, menopause, and hormone replacement, as well as those risk factors more common in women, such as obesity/metabolic syndrome, atrial fibrillation, and migraine with aura.

Conclusions—

To more accurately reflect the risk of stroke in women across the lifespan, as well as the clear gaps in current risk scores, we believe a female-specific stroke risk score is warranted.
Mice With Targeted Inactivation of
Ppap2b
in Endothelial and Hematopoietic Cells Display Enhanced Vascular Inflammation and Permeability
Authors: Panchatcharam Manikandan , Salous Abdel K. , Brandon Jason , Miriyala Sumitra , Wheeler Jessica , Patil Pooja , Sunkara Manjula , Morris Andrew J. , Escalante-Alcalde Diana , Smyth Susan S.
Published: February 2014

Objective—

Lipid phosphate phosphatase 3 (LPP3), encoded by the
PPAP2B
gene, is an integral membrane enzyme that dephosphorylates, and thereby terminates, the G-protein–coupled receptor–mediated signaling actions of lysophosphatidic acid (LPA) and sphingosine-1-phosphate. LPP3 is essential for normal vascular development in mice, and a common
PPAP2B
polymorphism is associated with increased risk of coronary artery disease in humans. Herein, we investigate the function of endothelial LPP3 to understand its role in the development and human disease.

Approach and Results—

We developed mouse models with selective LPP3 deficiency in endothelial and hematopoietic cells. Tyrosine kinase
Tek
promoter–mediated inactivation of
Ppap2b
resulted in embryonic lethality because of vascular defects. LPP3 deficiency in adult mice, achieved using a tamoxifen-inducible Cre transgene under the control of the Tyrosine kinase
Tek
promoter, enhanced local and systemic inflammatory responses. Endothelial, but not hematopoietic, cell LPP3 deficiency led to significant increases in vascular permeability at baseline and enhanced sensitivity to inflammation-induced vascular leak. Endothelial barrier function was restored by pharmacological or genetic inhibition of either LPA production by the circulating lysophospholipase D autotaxin or of G-protein–coupled receptor–dependent LPA signaling.

Conclusions—

Our results identify a role for the autotaxin/LPA-signaling nexus as a mediator of endothelial permeability in inflammation and demonstrate that LPP3 limits these effects. These findings have implications for therapeutic targets to maintain vascular barrier function in inflammatory states.
Systolic and Diastolic Mechanics in Stress Cardiomyopathy
Authors: Medeiros Keith , O’Connor Mark J. , Baicu Catalin F. , Fitzgibbons Timothy P. , Shaw Peter , Tighe Dennis A. , Zile Michael R. , Aurigemma Gerard P.
Published: February 2014

Background—

Stress cardiomyopathy (SCM) is a peculiar form of reversible left ventricular dysfunction seen predominantly in women and occurs in response to emotional or physical stress. Because dysfunction in SCM is reversible and that of acute myocardial infarction (MI) is not, we hypothesized that these fundamental mechanistic differences between SCM and MI would be associated with different systolic and diastolic properties.

Methods and Results—

We examined 3 groups, all women: patients with SCM (n=24; mean age, 63±12 years), those with left anterior (LAD) ST-segment–elevation MI (n=36; mean age, 63±10 years), and referent control subjects (n=30; mean age, 62±8 years). All underwent angiography, ventriculography, and pressure measurements within 48 hours of presentation. Left ventricular volumes, diastolic pressures, and diastolic stiffness were higher in SCM and LAD MI patients than in control subjects but no different from each other. Similarly, left ventricular diastolic pressures and diastolic stiffness were elevated in the SCM and LAD MI groups compared with the control group. Left ventricular ejection fraction in SCM and LAD MI were 40.8±12.3% and 49.6±5.6%, respectively, versus 70.4±9.4% in control subjects (
P
<0.001), and stroke work less than half the value of control subjects. Indexes of contractility and ventricular-arterial coupling were similarly abnormal in SCM and LAD MI.

Conclusions—

SCM and LAD MI show severe diastolic dysfunction. At similar left ventricular volumes, their diastolic pressures are more than twice as high as in control subjects, and systolic dysfunction is equally reduced in SCM and LAD MI. Despite a completely different pathophysiology in terms of systolic and diastolic function, SCM is indistinguishable from acute LAD-territory MI.
Impact of Pretreatment Noncontrast CT Alberta Stroke Program Early CT Score on Clinical Outcome After Intra-Arterial Stroke Therapy
Authors: Yoo Albert J. , Zaidat Osama O. , Chaudhry Zeshan A. , Berkhemer Olvert A. , González R. Gilberto , Goyal Mayank , Demchuk Andrew M. , Menon Bijoy K. , Mualem Elan , Ueda Dawn , Buell Hope , Sit Siu Po , Bose Arani
Published: February 2014

Background and Purpose—

The efficacy of intra-arterial treatment remains uncertain. Because most centers performing IAT use noncontrast CT (NCCT) imaging, it is critical to understand the impact of NCCT findings on treatment outcomes. This study aimed to compare functional independence and safety among patients undergoing intra-arterial treatment stratified by the extent of ischemic change on pretreatment NCCT.

Methods—

The study cohort was derived from multicenter trials of the Penumbra System. Inclusion criteria were anterior circulation proximal occlusion, evaluable pretreatment NCCT, and known time to reperfusion. Ischemic change was quantified using the Alberta Stroke Program Early CT Score (ASPECTS) and stratified into 3 prespecified groups for comparison: 0 to 4 (most ischemic change) versus 5 to 7 versus 8 to 10 (least ischemic change).

Results—

A total of 249 patients were analyzed: 40 with ASPECTS 0 to 4, 83 with ASPECTS 5 to 7, and 126 with ASPECTS 8 to 10. For ASPECTS 0 to 4, 5 to 7, and 8 to 10, respectively, good outcome (modified Rankin Scale score, 0–2) rates were 5%, 38.6%, and 46% (
P
<0.0001), and mortality rates were 55%, 28.9%, and 19% (
P
=0.0001). The only significant pairwise differences were between ASPECTS 0 to 4 and other groups. Symptomatic hemorrhage was more common with lower ASPECTS (
P
=0.02). Shorter time to reperfusion was significantly associated with better outcomes among patients with ASPECTS 8 to 10 (
P
=0.01). A similar relationship was seen for ASPECTS 5 to 7 but was not statistically significant. No such relationship was seen for ASPECTS 0 to 4.

Conclusions—

NCCT seems useful for excluding patients with the greatest burden of ischemic damage from futile intra-arterial treatment, which is unlikely to result in patient functional independence and increases the risk of hemorrhage.
Biotech Research-Tool Patents in Macedonia: Current Legal and Economic Parameters
Authors: Stankovic Mirjana , Stankovic Bratislav
Published: February 2014

One of the vigorously debated topics related to the protection of biotechnology inventions has been the issue of patents on biotechnology research tools, which usually are used in very early stages of biotechnology research. Proponents of patenting argue that the patent system acts as an incentive for biotech/pharma companies to invest in research and development which is aimed at developing biotech research tools. Opponents of patenting maintain that such patents might impede future research by creating “patent-thickets” and preventing researchers from performing experiments which rely on the patented tools without authorization and royalty payments.

The Republic of Macedonia is a small, developing country that lacks specifically crafted legislation or even an articulated public policy promoting the growth of the biotechnology sector. Macedonian patent law contains rather broad exemption to patent rights, termed in “free use for personal and non commercial purposes” and “free use for research and development” of a patented invention. These provisions use obfuscating language and might generate confusion and divergent judicial practices. Also problematic are the law’s provisions which pertain to biotechnology patents and, especially, exemptions to biotechnology patents; these appear to misinterpret the mirroring provisions of the European Union Biotechnology Directive.

This article argues in favor of amending the Macedonian industrial property law with a list of both specific exemptions and safeguards, which should provide clarity in future judicial practice pertaining to experimental-use exemptions of biotech research-tool patents in this country.
‘What Am I in a Boundless Creation?’
Authors: Marlow Hilary
Published: February 2014

Drawing on insights from the field of ‘ecocriticism’ within literary studies, this article examines the creation poem of Ben Sira (16.26-17.14) from an ecological perspective. The text is significant for such a purpose because of its reuse of the Genesis creation accounts, in particular the notion of human beings as the image of God and with dominion over creation, which has caused some critics to label the biblical accounts as exploitatively anthropocentric. Preceding sections of Sirach include discussion of human significance ‘in a boundless creation’ and human free will and moral responsibility, and these themes are developed in the poem itself. The poem’s description of the creation of humankind suggests both human finitude, a characteristic shared with other life forms, and the uniqueness of the divine image in human beings. These characteristics are set within the context of the cosmos as a stable and ordered whole, obedient to God, and of the responsibilities stipulated in the Torah to deal rightly with one’s neighbour. Reading this text from an ecological perspective invites recognition of the ambiguity of human place in the world, transient yet earth-changing, and of the ethical challenges in caring for global neighbours in the face of growing environmental pressures.
Our Father
Authors: Moore Michael Edward
Published: February 2014

This commentary on the Lord’s Prayer examines its tone of spiritual abandonment and cultural secondariness. The Our Father was a buttress of faith and liturgy for the medieval Church, while the prayer’s sense of desolation gives it a “bohemian” quality associated with poets and vagabonds. Later on, the Cathars adopted the Pater Noster as a “central text” having esoteric and spiritual importance. Although the Cathars were persecuted in the Middle Ages as heretics, their understanding of the Lord’s Prayer returns us to the prayer’s sense of isolation and cosmic abandonment.