bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term non-invasive ventilation therapies in children: a scoping review protocol
Authors: Castro Codesal Maria L , Featherstone Robin , Martinez Carrasco Carmen , Katz Sherri L , Chan Elaine Y , Bendiak Glenda N , Almeida Fernanda R , Young Rochelle , Olmstead Deborah , Waters Karen A , Sullivan Collin , Woolf Vicki , Hartling Lisa , MacLean Joanna E
Published: August 2015

Introduction

Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children.

Methods and analysis

We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two reviewers will independently screen titles and abstracts for inclusion, followed by full-text screening of potentially relevant articles to determine final inclusion. Data synthesis will be performed at three levels: (1) an analysis of the number, publication type, publication year, and country of publication of the studies; (2) a summary of the study designs, outcomes measures used; (3) a thematic analysis of included studies by subgroups.

Ethics and dissemination

This study will provide a wide and rigorous overview of the evidence on the use of long-term NIV in children and provide critical information for healthcare professionals and policymakers to better care for this group of children. We will disseminate our findings through conference proceedings and publications, and evaluate the results for further systematic reviews and meta-analyses.
Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: a cluster-randomised controlled trial protocol
Authors: Moyle Wendy , Beattie Elizabeth , Draper Brian , Shum David , Thalib Lukman , Jones Cindy , O'Dwyer Siobhan , Mervin Cindy
Published: August 2015

Introduction

Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care.

Methods and analysis

A cluster-randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush-Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants’ demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data.

Ethics and dissemination

The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer-reviewed journals.

Trial registration number

Australian and New Zealand Clinical Trials Registry number ACTRN12614000508673 date registered 13/05/2014.
Asymptotic geometry of discrete interlaced patterns: Part I
Authors: Duse Erik , Metcalfe Anthony
Published: August 2015

A discrete Gelfand–Tsetlin pattern is a configuration of particles in ℤ2. The particles are arranged in a finite number of consecutive rows, numbered from the bottom. There is one particle on the first row, two particles on the second row, three particles on the third row, etc., and particles on adjacent rows satisfy an interlacing constraint. We consider the uniform probability measure on the set of all discrete Gelfand–Tsetlin patterns of a fixed size where the particles on the top row are in deterministic positions. This measure arises naturally as an equivalent description of the uniform probability measure on the set of all tilings of certain polygons with lozenges. We prove a determinantal structure, and calculate the correlation kernel. We consider the asymptotic behavior of the system as the size increases under the assumption that the empirical distribution of the deterministic particles on the top row converges weakly. We consider the asymptotic "shape" of such systems. We provide parameterizations of the asymptotic boundaries and investigate the local geometric properties of the resulting curves. We show that the boundary can be partitioned into natural sections which are determined by the behavior of the roots of a function related to the correlation kernel. This paper should be regarded as a companion piece to the paper [E. Duse and A. Metcalfe, Asymptotic geometry of discrete interlaced patterns: Part II, in preparation], in which we resolve some of the remaining issues. Both of these papers serve as background material for the papers [E. Duse and A. Metcalfe, Universal edge fluctuations of discrete interlaced particle systems, in preparation; E. Duse and K. Johansson and A. Metcalfe, Cusp Airy process of discrete interlaced particle systems, in preparation], in which we examine the edge asymptotic behavior.
Reassessing the single relaxation time Lattice Boltzmann method for the simulation of Darcy’s flows
Authors: Prestininzi Pietro , Montessori Andrea , La Rocca Michele , Succi Sauro
Published: August 2015

It is shown that the single relaxation time (SRT) version of the Lattice Boltzmann (LB) equation permits to compute the permeability of Darcy’s flows in porous media within a few percent accuracy. This stands in contrast with previous claims of inaccuracy, which we relate to the lack of recognition of the physical dependence of the permeability on the Knudsen number.
Texture zero mass matrices and flavor mixing of quarks and leptons
Authors: Fritzsch Harald
Published: August 2015

We discuss mass matrices with four texture zeros for the quarks and leptons. The three mixing angles for the quarks and leptons are functions of the fermion masses. The results agree with the experimental data. The ratio of the masses of the first two neutrinos is given by the solar mixing angle. The neutrino masses are calculated: [Formula: see text], [Formula: see text] and [Formula: see text].
The shadow nature of positive and twisted quandle invariants of knots
Authors: Kamada Seiichi , Lebed Victoria , Tanaka Kokoro
Published: August 2015

Quandle cocycle invariants form a powerful and well-developed tool in knot theory. This paper treats their variations — namely, positive and twisted quandle cocycle invariants, and shadow invariants. We interpret the former as particular cases of the latter. As an application, several constructions from the shadow world are extended to the positive and twisted cases. Another application is a sharpening of twisted quandle cocycle invariants for multi-component links.
On unknotting operations of rotation type
Authors: Bae Yongju , Kim Byeorhi
Published: August 2015

An unknotting operation is a local move on a knot diagram such that any knot diagram can be transformed into a diagram of the unknot by a finite sequence of the operations and Reidemeister moves. In this paper, we introduce a new local move H(T) on a knot diagram which is obtained by the rotation of a tangle diagram T and study their properties. As an application, we prove that the H(T)-move is an unknotting operation for any descending tangle diagram T.
On knotted real projective planes
Authors: Bae Yongju , Choi Seonmi , Kawauchi Akio
Published: August 2015

Let [Formula: see text] be a hyperbolic transformation. Let B be a new band attaching to L such that [Formula: see text] is also a hyperbolic transformation. In this paper, we will study the relationship between the realizing surfaces [Formula: see text] and [Formula: see text]. If B is a noncoherent band to both L and [Formula: see text] such that [Formula: see text] is defined, then [Formula: see text] and [Formula: see text] are ambient isotopic, where RP2 is one of the standard real projective planes. We will study the triviality of [Formula: see text] because as an application, RP2 can untangle some knotted sphere [Formula: see text] with suitable conditions, when it is attached to [Formula: see text] by the connected sum.
Lower bound of the unknotting number of prime knots with up to 12 crossings
Authors: Kanenobu Taizo , Matsumura Satoshi
Published: August 2015

We list prime knots with up to 12 crossings having the property: the lower bound of the unknotting number cannot be decided by the signature or non-triviality but is given by either: (i) the condition of a 2-bridge knot with unknotting number one, (ii) the criteria using special values of the Jones, Q, or HOMFLYPT polynomials, or (iii) Wendt's formula. Then we can give new information to the table of unknotting numbers in "KnotInfo", a web-based table of knot invariants.
Credibilistic Clustering: The Model and Algorithms
Authors: Zhou Jian , Wang Qina , Hung C.-C. , Yi Xiajie
Published: August 2015

Fuzzy clustering is a widely used approach for data classification by using the fuzzy set theory. The probability measure and the possibility measure are two popular measures which have been used in the fuzzy [Formula: see text]-means algorithm (FCM) and the possibilistic clustering algorithms (PCAs), respectively. However, the numerical experiments revealed that FCM and its derivatives lack the intuitive concept of degree of belongingness, and PCAs suffer from the “coincident problem” and cannot provide very stable results for some data sets. In this study, we propose a new clustering algorithm, called the credibilistic clustering algorithm (CCA), based on the credibility measure. The credibility measure provides some unique properties which can solve the “coincident problem” and noise issue compared with the probability measure and possibility measure. Based on some randomly generated data sets, experimental results compared with FCM and PCA show that CCA can deal with the “coincident problem” with good clustering results, and it is more robust to noise than PCA.
Intuitionistic Fuzzy Linguistic Induced Ordered Weighted Averaging Operator for Group Decision Making
Authors: Xian Sidong , Xue Wenting , Zhang Jianfeng , Yin Yubo , Xie Qin
Published: August 2015

With respect to multiple attribute group decision making (MAGDM) problems, in which the attribute weights take the form of real numbers, and the attribute values take the form of intuitionistic fuzzy linguistic variables, a decision analysis approach is proposed. In this paper, we develop an intuitionistic fuzzy linguistic induce OWA (IFLIOWA) operator and analyze the properties of it by utilizing some operational laws of intuitionistic fuzzy linguistic variables. A new method based on the IFLIOWA operator for multiple attribute group decision making (MAGDM) is presented. Finally, a numerical example is used to illustrate the applicability and effectiveness of the proposed method.
A refinement of Vietoris’ inequality for cosine polynomials
Authors: Alzer Horst , Kwong Man Kam
Published: August 2015

Let [Formula: see text] with [Formula: see text] In 1958, Vietoris proved that [Formula: see text] We offer the following improvement of this result: The inequalities [Formula: see text] hold for all [Formula: see text] and [Formula: see text] if and only if [Formula: see text] where [Formula: see text]
Patterns in a generalized volume-filling chemotaxis model with cell proliferation
Authors: Ma Manjun , Wang Zhian
Published: August 2015

In this paper, we consider the following system [Formula: see text] which corresponds to the stationary system of a generalized volume-filling chemotaxis model with logistic source in a bounded domain in [Formula: see text] with zero Neumann boundary conditions. Here the parameters [Formula: see text] are positive and [Formula: see text], and [Formula: see text] denotes the outward unit normal vector of [Formula: see text]. With the priori positive lower- and upper-bound solutions derived by the Moser iteration technique and maximum principle, we apply the degree index theory in an annulus to show that if the chemotactic coefficient [Formula: see text] is suitably large, the system with [Formula: see text] admits pattern solutions under certain conditions. Numerical simulations of the pattern formation are shown to illustrate the theoretical results and predict the interesting phenomenon for further studies.
New Information in Trending Topics of Tweets by Labelled Clusters
Authors: Madani Amina , Boussaid Omar , Zegour Djamel Eddine
Published: August 2015

Twitter is a popular micro-blogging service, and one of the main means of spreading ideas and information throughout the web. In this system, participants post short status messages called tweets that are often available publicly. Recently, the exponential growth of tweets has started to draw the attention of researchers from various disciplines. Numerous research approaches in the data mining field have examined Twitter. How to automatically extract useful information from tweets has therefore become an important research topic. The aim of this paper is to bring up what's up which is a new approach of tweets mining. It is a more general approach that discovers many different trending topics from tweets in real-time. Trending topics have generated big interest not only for the users of Twitter but also for information seekers. Our trending topics are detected for a specific geographic town and compared with the top trending topics shown on Twitter. They are presented by labelled clusters that constitute an accurate description of each trending topic. Each cluster is labelled by an emerging trending topic and is composed of keywords that represent the properties of the trending topic.
The Synergistic Effects of Knowledge Sharing and Learning on Organisational Learning: Demonstrating Organisational Performance
Authors: Khan Muhammad Omer Nadeem , ur Rahman Saleem , Khan Mohammad Bashir
Published: August 2015

Advancement in technologies has moved organisations from the traditional methods of strategic and tactical formulations to knowledge-based fabricated methods and strategies. Nowadays, knowledge management became an important success reason for the formulation of any strategy of every company. This knowledge dependent trend is not only dominant in developed economies and their firms, but also has attracted and motivated businesses operating in developing countries. Aiming on the degree of knowledge management influence, this study primarily tried to look at the effects of knowledge sharing (KS) on knowledge learning (KL) and organisational learning (OL), and to see the effect of OL on organisational learning culture (OLC) influencing the business performance. A research survey was conducted and obtained 214 (71%) valid responses from the sample of 500 respondents of the sales departments of six telecommunication companies. The Model fit Structural Equation Modelling (SEM) results show a positive effect of KS on KL and OL; however, KL effect on OL is insignificant. Consequently, the data did not support the effect of OL on OLC. However, OLC positively influenced organisational performance (OP). The results may guide the telecommunication companies to improve their knowledge management activities for better performance. The discussion and conclusions, managerial implications, and future research recommendations are presented at the end.
Quantum correlations in Heisenberg XY spin-1 and spin-1/2 model with Dzyaloshinskii–Moriya interactions
Authors: Joyia Wajid Hussain
Published: August 2015

We study the quantum correlations in a spin-1/2 (qubit) and spin-1 (qutrit) Heisenberg XY model separately, based on quantum discord (QD) and measurement-induced disturbance (MID) respectively. We find the evidence of the first- and second-order quantum phase transition (QPT) in both spin-1/2 and spin-1 systems. The effect of the temperature, magnetic field and Dzyaloshinskii–Moriya (DM) interactions on QPT and quantum correlation are also investigated. Finally, we observed that the QD and MID are not only vigorous for higher spin systems but also more robust than entanglement.
The Impact of New Scientific Knowledge on Firms’ Routines and Capabilities: The Case of Mechatronics
Authors: Rizzo Ugo , Freddi Daniela , Ramaciotti Laura
Published: August 2015

Routines and capabilities are patterns of actions, entailing both stability and change, according to which organizational behavior is investigated and that rest at the base of firms’ competitive advantage. Research in organizational theory recently started to disentangle the micro-foundations of these collective concepts in order to better grasp the mechanisms by which individuals influence the generation and evolution of routines and capabilities. In the present work we seek to contribute to this literature by investigating how the acquisition of a radical new body of knowledge via recruitment impacts on the evolution of the routines and dynamic capabilities of the firm. By means of a multiple case study research on mechatronics companies located in Northern Italy, the study examines if and how the insertion of graduates in a discipline new to the company modified its routines and the dynamic capabilities. In other words we explored whether the introduction of a new body of knowledge embodied in new graduates produced changes on the organization and functioning of the hosting R&D department and/or it also shaped the overall firm’s development strategies, thus overcoming the expected inertia. The results are important for both managing change to increase the company’s competitive advantage as well for the policy implications which can be derived.
Exotica or the failure of the strong cosmic censorship in four dimensions
Authors: Etesi Gábor
Published: August 2015

In this paper, a generic counterexample to the strong cosmic censor conjecture is exhibited. More precisely — taking into account that the conjecture lacks any precise formulation yet — first we make sense of what one would mean by a "generic counterexample" by introducing the mathematically unambigous and logically stronger concept of a "robust counterexample". Then making use of Penrose' nonlinear graviton construction (i.e. twistor theory) and a Wick rotation trick we construct a smooth Ricci-flat but not flat Lorentzian metric on the largest member of the Gompf — Taubes uncountable radial family of large exotic ℝ4's. We observe that this solution of the Lorentzian vacuum Einstein's equations with vanishing cosmological constant provides us with a sort of counterexample which is weaker than a "robust counterexample" but still reasonable to consider as a "generic counterexample". It is interesting that this kind of counterexample exists only in four dimensions.
DIVERSITY AND CHANGE OF USER DRIVEN INNOVATION MODES IN COMPANIES
Authors: HYYSALO SAMPSA , REPO PETTERI , TIMONEN PÄIVI , HAKKARAINEN LOUNA , HEISKANEN EVA
Published: August 2015

User driven innovation (UDI) is a popular term in policy and corporate circles. However, it is not clear exactly what UDI means and how such practices are used across the spectrum of companies and over the innovation life cycle. The present study compares 58 UDI showcases in Finnish companies in order to analyse the diversity of UDI practices and their evolution over time. We identify five main modes of UDI and show how the ways of using UDI develop over time in individual companies. In almost half of the examined cases, the dominant mode of UDI changes at least once, and in some cases, up to three changes in dominant mode are observed. We then proceed to identify six qualitatively different ways in which companies’ orientation to UDI evolves over time. The study has implications for innovation management and policy: It calls for greater attention to UDI diversity and particularly to the management and support of the continuity of UDI efforts.
UNDERSTANDING LINEAR AND NONLINEAR ASPECTS OF PRODUCT CONCEPT DEVELOPMENT FROM THE ORGANISATIONAL INTERPRETATION PERSPECTIVE
Authors: MIYAO MANABU
Published: August 2015

The product concept is crucial in new product development (NPD) because it represents an NPD project’s goal. In this context, most prior studies have regarded product concept development as a linear process but some recent studies have revealed that it also has nonlinear characteristics. The objective of this paper is to explore why this inconsistency has arisen and to develop a model and theory that illustrate both aspects of product concept development. To achieve this, we adopt the perspective of organisational interpretation systems (Daft and Weick (1984). Toward a model of organisations as interpretation systems. Academy of Management Review, 9(2), 289–295) and explore eight product development cases. Consequently, we develop a three-stage model and find that the linearity or nonlinearity of product concept development is determined by each NPD team’s assumption about the environment. We also consider product innovativeness and function equivocality, and establish that these are related to the NPD teams’ assumptions about the environment.
Synthesis, structure and photoluminescent behavior of a novel pillar-layered {Zn3}-based metal–organic framework
Authors: Song Xue-Zhi , Mu Wen-Sheng , Han Bing-Yan , Yan Yang
Published: August 2015

A novel 3D metal–organic framework (MOF) {[Zn3(bpdc)3 (p-4-bpmb)](DMF)2}n ( 1) (H[Formula: see text]-4,4′-dicarboxylic acid; p-4-[Formula: see text],4-bis(pyridine-4-ylmethoxy)benzene) has been solvothermally synthesized and structurally characterized. Compound 1 exhibits a 3D pillar-layered framework based on the trinuclear {Zn3} building blocks, consisting of Zn-dicarboxylate layers and bipyridyl-derivative pillars. Furthermore, it features three-fold interpenetrating 8-connected hex-type topology. In addition, its thermal stability and luminescent property have also been investigated.
The Archaeology of Ritual
Authors: Swenson Edward
Published: August 2015

The main objective of this review is to consider what archaeology can contribute to general anthropological theories on “ritual in its own right” and to highlight the potential for advancing knowledge about ritual experience as a distinctive material process. An examination of the exceptional material frame marking ceremonial events demonstrates the value of ritual as a heuristic and challenges archaeologists who privilege the interpretation of religion, affect, ontology, or cultural rationalities as necessarily determinative of the ritualization process. Therefore, archaeologists should not interpret ritual places and residues as immediate proxies of other sociopolitical realities but instead should base their inferences on cross-contextual analyses of archaeological data sets. Ultimately, attention to the amplified materialization of the ritual process, often entailing the performative bundling of disparate material items in archaeological deposits, permits a re-evaluation of theories proposing that ritual is intimately connected to agency and power.
Properties of the Higgs Boson Discovered at the Large Hadron Collider
Authors: Murray William , Sharma Vivek
Published: August 2015

In their search for the Standard Model (SM) Higgs boson, the ATLAS and CMS Collaborations discovered a narrow bosonic particle with a mass of approximately 125 GeV during the first Large Hadron Collider run. In this article, we discuss the search methodologies that led to this discovery as well as the precise measurements of the mass of this boson, constraints on its intrinsic width, its production rate, its coupling to several SM particles, and tests of its spin-parity quantum numbers. All the properties of this boson, within measurement uncertainties, are remarkably consistent with those of the SM Higgs boson.
Materialistic Values and Goals
Authors: Kasser Tim
Published: August 2015

Materialism comprises a set of values and goals focused on wealth, possessions, image, and status. These aims are a fundamental aspect of the human value/goal system, standing in relative conflict with aims concerning the well-being of others, as well as one's own personal and spiritual growth. Substantial evidence shows that people who place a relatively high priority on materialistic values/goals consume more products and incur more debt, have lower-quality interpersonal relationships, act in more ecologically destructive ways, have adverse work and educational motivation, and report lower personal and physical well-being. Experimentally activating materialistic aims causes similar outcomes. Given these ills, researchers have investigated means of decreasing people's materialism. Successful interventions encourage intrinsic/self-transcendent values/goals, increase felt personal security, and/or block materialistic messages from the environment. These interventions would likely be more effective if policies were also adopted that diminished contemporary culture's focus on consumption, profit, and economic growth.
Relation between QT interval variability and muscle sympathetic nerve activity in normal subjects
Authors: El-Hamad Fatima , Lambert Elisabeth , Abbott Derek , Baumert Mathias
Published: August 2015

Beat-to-beat variability of the QT interval (QTV) is sought to provide an indirect noninvasive measure of sympathetic nerve activity, but a formal quantification of this relationship has not been provided. In this study we used power contribution analysis to study the relationship between QTV and muscle sympathetic nerve activity (MSNA). ECG and MSNA were recorded in 10 healthy subjects in the supine position and after 40° head-up tilt. Power spectrum analysis was performed using a linear autoregressive model with two external inputs: heart period (RR interval) variability (RRV) and MSNA. Total and low-frequency power of QTV was decomposed into contributions by RRV, MSNA, and sources independent of RRV and MSNA. Results show that the percentage of MSNA power contribution to QT is very small and does not change with tilt. RRV power contribution to QT power is notable and decreases with tilt, while the greatest percentage of QTV is independent of RRV and MSNA in the supine position and after 40° head-up tilt. In conclusion, beat-to-beat QTV in normal subjects does not appear to be significantly affected by the rhythmic modulations in MSNA following low to moderate orthostatic stimulation. Therefore, MSNA oscillations may not represent a useful surrogate for cardiac sympathetic nerve activity at moderate levels of activation, or, alternatively, sympathetic influences on QTV are complex and not quantifiable with linear shift-invariant autoregressive models.
Axl modulates immune activation of smooth muscle cells in vein graft remodeling
Authors: Batchu Sri N. , Xia Jixiang , Ko Kyung Ae , Doyley Marvin M. , Abe Jun-Ichi , Morrell Craig N. , Korshunov Vyacheslav A.
Published: August 2015

The pathophysiological mechanisms of the immune activation of smooth muscle cells are not well understood. Increased expression of Axl, a receptor tyrosine kinase, was recently found in arteries from patients after coronary bypass grafts. In the present study, we hypothesized that Axl-dependent immune activation of smooth muscle cells regulates vein graft remodeling. We observed a twofold decrease in intimal thickening after vascular and systemic depletion of Axl in vein grafts. Local depletion of Axl had the greatest effect on immune activation, whereas systemic deletion of Axl reduced intima due to an increase in apoptosis in vein grafts. Primary smooth muscle cells isolated from Axl knockout mice had reduced proinflammatory responses by prevention of the STAT1 pathway. The absence of Axl increased suppressor of cytokine signaling (SOCS)1 expression in smooth muscle cells, a major inhibitory protein for STAT1. Ultrasound imaging suggested that vascular depletion of Axl reduced vein graft stiffness. Axl expression determined the STAT1-SOCS1 balance in vein graft intima and progression of the remodeling. The results of this investigation demonstrate that Axl promotes STAT1 signaling via inhibition of SOCS1 in activated smooth muscle cells in vein graft remodeling.
Regular exercise improves cardiac contractile activation by modulating MHC isoforms and SERCA activity in orchidectomized rats
Authors: Vutthasathien Pavarana , Wattanapermpool Jonggonnee
Published: August 2015

Data from the trial known as Testosterone in Older Men with Mobility Limitations (TOM) has indicated an association between testosterone administration and a greater risk for adverse cardiovascular events. We therefore propose that regular exercise is a cardioprotective alternative that prevents detrimental changes in contractile activation when a deficiency in male sex hormones exists. Ten-week-old orchidectomized (ORX) rats were subjected to a 9-wk treadmill running program at moderate intensity starting 1 wk after surgery. Although exercise-induced cardiac hypertrophy was observed both in rats that underwent ORX and sham surgery, regular exercise enhanced cardiac myofilament Ca2+sensitivity and myosin light-chain 2 phosphorylation only in rats that underwent a sham operation. Although the rats that had sham surgery and and given exercise exhibited no change in maximum developed tension, regular running prevented the suppression of maximum active tension in the hearts of ORX rats. Regular exercise also prevented a shift in myosin heavy chain (MHC) isoforms toward β-MHC, a reduction in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity, and an increase in SERCA sensitivity in the hearts of ORX rats. Neither SERCA content nor its modulating component, phospholamban (PLB), was altered by exercise in either sham-operated or ORX rats. However, decreases in the phosphorylated Thr17form of PLB and the phosphorylated Thr287form of Ca2+/calmodulin-dependent kinase II in the hearts of ORX rats were abolished after regular exercise. These results thus support the use of regular running as a cardioprotective alternative to testosterone replacement in hypogonadal conditions.
New genetic and physiological factors for excessive erythrocytosis and Chronic Mountain Sickness
Authors: Villafuerte Francisco C.
Published: August 2015

In the last few years, genetic and functional studies have provided important insight on the pathophysiology of excessive erythrocytosis (EE), the main sign of Chronic Mountain Sickness (CMS). The recent finding of the association of the CMS phenotype with a single-nucleotide polymorphism (SNP) in the Sentrin-specific Protease 1 ( SENP1) gene, and its differential expression pattern in Andean highlanders with and without CMS, has triggered large interest in high-altitude studies because of the potential role of its gene product in the control of erythropoiesis. The SENP1 gene encodes for a protease that regulates the function of hypoxia-relevant transcription factors such as Hypoxia-Inducible Factor (HIF) and GATA, and thus might have an erythropoietic regulatory role in CMS through the modulation of the expression of erythropoietin (Epo) or Epo receptors. The different physiological patterns in the Epo-EpoR system found among Andeans, even among highlanders with CMS, together with their different degrees of erythropoietic response, might indicate specific underlying genetic backgrounds, which in turn might reflect different levels of adaptation to lifelong high-altitude hypoxia. This minireview discusses recent genetic findings potentially underlying EE and CMS, and their possible physiological mechanisms in Andean highlanders.
Human Amniotic Fluid Mesenchymal Stem Cells from Second- and Third-Trimester Amniocentesis: Differentiation Potential, Molecular Signature, and Proteome Analysis
Authors: Savickiene Jurate , Treigyte Grazina , Baronaite Sandra , Valiuliene Giedre , Kaupinis Algirdas , Valius Mindaugas , Arlauskiene Audrone , Navakauskiene Ruta
Published: August 2015

Human amniotic fluid stem cells have become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to characterize amniotic fluid-derived mesenchymal stem cells (AF-MSCs) from second- and third-trimester of gestation. Using two-stage protocol, MSCs were successfully cultured and exhibited typical stem cell morphological, specific cell surface, and pluripotency markers characteristics. AF-MSCs differentiated into adipocytes, osteocytes, chondrocytes, myocytes, and neuronal cells, as determined by morphological changes, cell staining, and RT-qPCR showing the tissue-specific gene presence for differentiated cell lineages. Using SYNAPT G2 High Definition Mass Spectrometry technique approach, we performed for the first time the comparative proteomic analysis between undifferentiated AF-MSCs from late trimester of gestation and differentiated into myogenic, adipogenic, osteogenic, and neurogenic lineages. The analysis of the functional and expression patterns of 250 high abundance proteins selected from more than 1400 demonstrated the similar proteome of cultured and differentiated AF-MSCs but the unique changes in their expression profile during cell differentiation that may help the identification of key markers in differentiated cells. Our results provide evidence that human amniotic fluid of second- and third-trimester contains stem cells with multilineage potential and may be attractive source for clinical applications.
Towards a Next-Generation Sequencing Diagnostic Service for Tumour Genotyping: A Comparison of Panels and Platforms
Authors: Burghel George J. , Hurst Carolyn D. , Watson Christopher M. , Chambers Phillip A. , Dickinson Helen , Roberts Paul , Knowles Margaret A.
Published: August 2015

Detection of clinically actionable mutations in diagnostic tumour specimens aids in the selection of targeted therapeutics. With an ever increasing number of clinically significant mutations identified, tumour genetic diagnostics is moving from single to multigene analysis. As it is still not feasible for routine diagnostic laboratories to perform sequencing of the entire cancer genome, our approach was to undertake targeted mutation detection. To optimise our diagnostic workflow, we evaluated three target enrichment strategies using two next-generation sequencing (NGS) platforms (Illumina MiSeq and Ion PGM). The target enrichment strategies were Fluidigm Access Array custom amplicon panel including 13 genes (MiSeq sequencing), the Oxford Gene Technologies (OGT) SureSeq Solid Tumour hybridisation panel including 60 genes (MiSeq sequencing), and an Ion AmpliSeq Cancer Hotspot Panel including 50 genes (Ion PGM sequencing). DNA extracted from formalin-fixed paraffin-embedded (FFPE) blocks of eight previously characterised cancer cell lines was tested using the three panels. Matching genomic DNA from fresh cultures of these cell lines was also tested using the custom Fluidigm panel and the OGT SureSeq Solid Tumour panel. Each panel allowed mutation detection of core cancer genes includingKRAS,BRAF, andEGFR. Our results indicate that the panels enable accurate variant detection despite sequencing from FFPE DNA.
Estimation of the Impact of Meningococcal Serogroup C Universal Vaccination in Italy and Suggestions for the Multicomponent Serogroup B Vaccine Introduction
Authors: Martinelli Domenico , Fortunato Francesca , Cappelli Maria Giovanna , Cozza Vanessa , Chironna Maria , Prato Rosa
Published: August 2015

In Italy, the meningococcal C conjugate vaccine (MenC) has been offered in most regions since 2009-2010. The incidence of Invasive Meningococcal Disease (IMD) was 0.25 confirmed cases per 100,000 in 2011, but this may be considerably underestimated due to underdetection and underreporting. This study estimates the impact of the MenC universal vaccination (URV) in the Puglia region by assessing the completeness of three registration sources (notifications, hospitalizations, and laboratory surveillance). Capture-recapture analysis was performed on meningococcal meningitis collected within 2001–2013. The impact of URV among≤18-year-olds was assessed by attributable benefit, preventable fraction, and prevented fraction. Missed opportunities for vaccination were evaluated from surveillance of IMD. The proportion of detected serogroups was applied to the number of IMD in the postvaccination period to compute the cases still preventable. The sensitivity of the three sources was 36.7% (95% CI: 17.5%–57.9%) and registrations lost nearly 28 cases/year in the period. Attributable benefit of URV was −0.5 cases per 100,000, preventable fraction 19.6%, and prevented fraction 31.3%. Three adolescent cases missed the opportunity to be vaccinated. The multicomponent serogroup B meningococcal vaccine has the potential to further prevent at least three other cases/year. Vaccination strategy against serogroup B together with existing programmes makes IMD a 100% vaccine-preventable disease.
CCR 20th Anniversary Commentary: Divide and Conquer—Breast Cancer Subtypes and Response to Therapy
Authors: Pusztai Lajos , Rouzier Roman , Symmans W. Fraser
Published: August 2015

The article by Rouzier and colleagues, published in the August 15, 2005, issue of Clinical Cancer Research, demonstrated that different molecular subtypes of breast cancer have different degrees of sensitivity to chemotherapy, but the extent of response to neoadjuvant therapy has a different meaning by subtype. Several molecular subtype–specific clinical trials are under way to maximize pathologic complete response rates in triple-negative breast cancer and HER2-positive cancers, and to provide adjuvant treatment options for patients with residual invasive disease. Clin Cancer Res; 21(16); 3575–7. ©2015 AACR.

See related article by Rouzier et al., Clin Cancer Res 2005;11(16) Aug 15, 2005;5678–85
Prevalence of the UGT1A1*6 (c.211G>A) Polymorphism and Prediction of Irinotecan Toxicity in Iranian Populations of Different Ethnicities
Authors: Shakibi Reyhaneh , Kamalidehghan Behnam , Ahmadipour Fatemeh , Meng Goh Yong , Houshmand Massoud
Published: August 2015

Background: Pharmacogenetic studies on irinotecan treatment in patients with metastatic colorectal cancer have indicated that genetic polymorphisms in UGT1A1*6 can lead to decreased enzyme activity and accumulation of the toxic metabolite SN-38. Here, we compared the prevalence of UGT1A1*6 in an Iranian population of different ethnicities with those of other populations. Materials and Methods: A total of 300 healthy people of different ethnic groups including Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian in the Iranian population were enrolled. Genotyping of the UGT1A1*6 alleles (G/G, A/G, A/A) was performed by polymerase chain reaction-restriction fragment length polymorphism and direct genomic DNA sequencing. Result: The most predictive genotype among the Iranian ethnic groups, especially Persian, was the G/G genotype (wild-type genotype). The frequency of the A/G genotype among the Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian ethnicities were 15.69% (n = 27), 11.11% (n = 8), 5.88% (n = 1), 9.09% (n = 1), 10% (n = 1), 20% (n = 1) and 0% (n = 0), respectively. Only one person with Persian ethnicity was homozygous for the mutation in UGT1A1*6 (0.58%). Additionally, the frequency of the A and G alleles in Iranians was 6.83 and 93.16%, respectively. Conclusion: The identification of the UGT1A1*6 alleles is necessary among the different Iranian ethnic groups before irinotecan therapy, suggesting that genotyping would be helpful for clinicians to optimize chemotherapy or identify individuals at risk of adverse drug reactions before clinical trials.
Bevacizumab-Based Therapy for Patients with Brain Metastases from Non-Small-Cell Lung Cancer: Preliminary Results
Authors: Zustovich Fable , Ferro Alessandra , Lombardi Giuseppe , Farina Patrizia , Zagonel Vittorina
Published: August 2015

Background: Bevacizumab is a recombinant humanized monoclonal antibody that obstructs the vascular endothelial growth factor (VEGF) pathway. Despite its extensive employment in the treatment of primary tumors of the brain, experience of brain metastatic disease, a frequent complication in patients with lung cancer, is very limited. On the basis of the strong antiedemigenous effect and no risk of intracranial bleeding, we administered a bevacizumab-based chemotherapy to patients with non-small-cell lung cancer (NSCLC) and symptomatic metastatic brain lesions who were not suitable candidates for a specific local therapy. Methods: The patients received bevacizumab 7.5 mg/kg and cisplatin 75 mg/m2 on day 1, and gemcitabine 1,250 mg/m2 on days 1 and 8, every 21 days. Results: We studied 13 patients with clinical and radiological progressive brain metastases; the majority had a treatment-naïve disease. Bevacizumab-based chemotherapy was found to be well tolerated and effective: progression-free survival (PFS) was 9.1 months (range: 0.9-39.2+) and overall survival (OS) was 9.6 months (range 3-41.5+). Conclusions: Bevacizumab-based therapy proved to be feasible and safe. The PFS and the OS data are very encouraging as well as the symptomatic benefit due to bevacizumab's high capacity to provide a long-lasting decrease of perilesional edema.
Exploiting AT2R to Improve CD117 Stem Cell Function In Vitro and In Vivo - Perspectives for Cardiac Stem Cell Therapy
Authors: Ludwig Marion , Tölk Anita , Skorska Anna , Maschmeier Christian , Gaebel Ralf , Lux Cornelia Aquilina , Steinhoff Gustav , David Robert
Published: August 2015

Background/Aims: CD117+ stem cell (SC) based therapy is considered an alternative therapeutic option for terminal heart disease. However, controversies exist on the effects of CD117+ SC implantation. In particular, the link between CD117+ SC function and angiotensin-II-type-2 receptor (AT2R) after MI is continuously discussed. We therefore asked whether 1) AT2R stimulation influences CD117+ SC properties in vitro and, 2) which effects can be ascribed to AT2R stimulation in vivo. Methods: We approached AT2R stimulation with Angiotensin II while simultaneously blocking its opponent receptor AT1 with Losartan. CD117 effects were dissected using a 2D-Matrigel assay and HL-1 co-culture in vitro. A model of myocardial infarction, in which we implanted EGFP+ CD117 SC, was further applied. Results: While we found indications for AT2R driven vasculogenesis in vitro, co-culture experiments revealed that CD117+ SC improve vitality of cardiomyocytes independently of AT2R function. Likewise, untreated CD117+ SC had a positive effect on cardiac function and acted cardioprotective in vivo. Conclusions: Therefore, our data show that transient AT2R stimulation does not significantly add to the beneficial actions of CD117+ SC in vivo. Yet, exploiting AT2R driven vasculogenis via an optimized AT2R stimulation protocol may become a promising tool for cardiac SC therapy.
Novel Clinical Manifestation of the Known SCN5A D1790G Mutation
Authors: Blich Miry , Efrati Edna , Marai Ibrahim , Suleiman Mahmoud , Gepstein Lior , Boulous Monther
Published: August 2015

The D1790G mutation was found in all 24 patients of an extended long QT family but not in 200 chromosomes carried by healthy individuals. We describe a 37-year-old man presenting with a typical spontaneous type 1 Brugada pattern who in electrophysiological testing had easily inducible ventricular fibrillation. At the age of 47 years he had an atrial ventricular type 2 block documented by an exercise test and a Holter monitor. Genetic analysis revealed a known D1790G mutation in the gene encoding of the sodium channel (SCN5A) that until now has been associated only with the long QT phenotype. Although this mutation has not been associated with a reduction of sodium channel expression, we hypothesize that sodium currents are further diminished due to the 20-mV shift of the steady-state inactivation curve, and this could contribute to the Brugada phenotype. This case is important as it allows a better understanding of the underlying molecular mechanisms of Brugada syndrome. Moreover, this observation raises concern about the safety of class IC drug therapy in long QT type 3 patients and quinidine therapy in Brugada patients, and emphasizes the importance of a thorough clinical and genetic evaluation.
Gastrointestinal Lymphoma in Southwest China: Subtype Distribution of 1,010 Cases Using the WHO (2008) Classification in a Single Institution
Authors: Ding Wenshuang , Zhao Sha , Wang Jianchao , Yang Qunpei , Sun Hong , Yan Jiaqi , Gao Limin , Yao Wenqing , Zhang Wenyan , Liu Weiping
Published: August 2015

The gastrointestinal tract (GIT) is the most common anatomic site of extranodal non-Hodgkin lymphoma (NHL) involvement. The classification criteria of lymphoma have changed in recent decades, and few large-sample studies regarding subtype analysis of lymphoma have been performed in this site. Aim: Therefore, the present study was conducted to analyze the histological subtype distribution of the GIT. Method: All patients in a single institution with a diagnosis of primary NHL in the GIT were enrolled between January 2007 and April 2014. The patients were categorized according to the WHO (2008) classification of tumors of hematopoietic and lymphoid tissue. Result: A total of 1,010 eligible cases diagnosed as NHL were collected in this study. The male:female ratio was 1.7:1 and the median age was 55 years. The percent of patients with lymphoma involvement in the stomach was 52% (n = 522), and the remaining 48% (n = 484) had intestinal tract involvement. Histologically, diffuse large B cell lymphoma (DLBCL) was the most common subtype in all of the GIT lymphoma cases, and was also the most common subtype in cases involving the stomach (78%) and the intestinal tract (53%). The incidence of DLBCL and mucosa-associated lymphoid tissue lymphoma in the stomach was significantly higher than the incident in the intestinal tract (p < 0.01). T and NK cell lymphoma was significantly more common in the intestinal tract than in the stomach (p < 0.01). Extranodal NK/T cell lymphoma nasal type (ENKTL-N) was the most common subtype of T and NK cell lineage lymphoma in GIT and was also the second most common intestinal tract-involved lymphoma. Conclusion: DLBCL was the most frequent lymphoma in the stomach and in the intestinal tract. T and NK cell lineage lymphoma had a higher occurrence in the intestinal tract than in the stomach. ENKTL-N was the most frequent subtype of lymphoma derived from NK/T cell lineage, and was the second most common lymphoma among all intestinal tract lymphomas.