bluuebunny/crossref_metadata_2025 huggingface dataset:
Food Product Traceability and Customer Value
Authors: Engelseth Per , Wongthatsanekorn Wuthichai , Charoensiriwath Chayakrit
Published: November 2014

A customer value-oriented approach is applied to analyze a case study of an ongoing project in rural Thailand to trace quality produce supplied to upmarket retail in the same country. Traceability, an organizational competence, is seldom in business practice as well as in the literature associated with value. It has been stressed through this study that traceability systems involve more than technical and cost-related challenges. Aspects of traceability as a value-related knowledge resource are evoked through viewing traceability as embedded in a ‘value network’ construct. This view is applied to a food network in a developing economy. In addition, the case study reveals the impact of new technology, how traceability is organized and costs of this organization in a value network. Food product traceability is described as an organized supply chain resource, not limited to IT-related costs driven by needs to succumb to government requirements, which is also applicable in developing economies due to market development and lower IT costs. This customer value-based understanding is of importance when considering investing in traceability and in the design of food product traceability systems, as well as lowering hindrances associated with developing electronic food product traceability using new information technology.
A Symbiotic Coexistence
Authors: Hoffmann Michael Peter
Published: November 2014

The aim of this article is to contribute to our understanding of how the Nepalese Maoist movement intersects with non-Maoist trade unions. I challenge dominant views of an enduring antagonism between the Nepalese Maoist movement and non-Maoist trade unions. Instead, I contend that for an urban municipality in the western tarai, the Maoist movement and non-Maoist labour unions co-reside, in a symbiotic relationship, within the boundaries of the town. I highlight how, while Maoists claim to represent labour in general, their actions focus largely on the protection of a specific segment of the town’s labour force. Maoists offer political patronage to formerly bonded labourers’ neighbourhoods but neglect other labour concerns. This political vacuum surrounding the representation of labour has instead been filled by two non-Maoist labour unions that emerged in the wake of the insurgency period. I document the development of these groups and look at the various forms of collective action they employ, which include strikes, the mediation of labour disputes, monthly union meetings and the institutionalization of collective bargaining procedures. I suggest that an important effect of the new trade unionism in town is the incorporation of formerly bonded labourers into the unions’ power structures.
Determinants of Livelihood Choices
Authors: Rahman Sanzidur , Akter Shaheen
Published: November 2014

The study identifies socio-economic determinants of livelihood choices of rural households in Bangladesh (4,195 households from 139 villages) by applying a multinomial logit model of occupational choice and a multivariate Tobit model that allows for jointness in decision making. Results reveal that households choose multiple livelihood options. A number of socio-economic factors and resources at the household level as well as the state of rural infrastructure significantly determine households’ livelihood choice. Overall, resource-rich and educated households engage in diversified livelihoods and rural infrastructure promotes such diversification. Female-headed households fail to participate in any of the livelihood categories and consequently earn significantly lower income. Policy implications include investment in rural infrastructure, irrigation, rural electrification, education, livestock resources, as well as targeting of female-headed households, for example, creation of a hired labour market and skills/education programmes for females.
Social Media in Advertising Campaigns
Authors: Voorveld Hilde A.M. , van Noort Guda
Published: November 2014

Inspired by the increasing popularity of advertising on social media, and especially on social network sites (SNSs), the aim of this study is to give insight into the effectiveness of SNS advertising. The first experimental study compares consumer responses to advertising on SNSs and television (TV) and demonstrates that while TV campaigns are evaluated more positively, SNS campaigns result in more favourable cognitive responses. Moreover, the persuasive intent of SNS campaigns is less recognized than for TV campaigns. Since SNSs are often combined with traditional media in advertising campaigns, the second study examines whether campaigns combining TV and SNSs lead to so-called synergy effects. Results showed that this was not the case: single-medium and multimedia campaigns were equally effective. The third study examines the role of perceived persuasive intent in this relationship and tests whether there is an indirect effect of type of campaign (multimedia or single-medium) on consumer responses via perceived persuasive intent. Results show that SNS–TV campaigns are perceived as less persuasive than SNS-only and TV-only campaigns, resulting in more favourable campaign and brand responses. In sum, the article provides empirical evidence for the value of integrating social media with traditional media in advertising campaigns.
Book Review: Keya Acharya and Frederick Noronha, The Green Pen: Environmental Journalism in India and South Asia
Authors: Sinha Arbind
Published: November 2014

Keya Acharya and Frederick Noronha, The Green Pen: Environmental Journalism in India and South Asia. New Delhi: SAGE Publications. 2009, 312 pages, ₹ 295.
SV-waves incidence at interface between solid-liquid media under magnetic field, initial stress and two thermal relaxation times
Authors: Abo-Dahab SM , Abd-Alla AM , Marin M
Published: November 2014

In this paper we investigated the propagation of SV-waves under effect of the magnetic field, initial stress and two thermal relaxation times. The problem of reflection and transmission of thermoelastic waves at a solid-liquid interface in presence of initial stress and magnetic field has been investigated subjected to certain boundary conditions. The appropriate expressions to find the amplitudes ratios for the incident wave (SV-waves) have been obtained. The reflection and transmitted coefficients for the incident SV-waves are computed numerically, considering the initial stress, relaxation times, and magnetic field effect and presented graphically. The results indicate that the effects of magnetic field, initial stress and two thermal relaxation times are very pronounced.
Influence of temperature on optimum viscoelastic absorbers in cubic nonlinear systems
Authors: Febbo Mariano , Lopes Eduardo MO , Bavastri CA
Published: November 2014

Recently, viscoelastic materials have been widely used for vibration control due to their efficacy and flexibility in real engineering problems. Their use as constitutive parts of dynamic vibration absorbers requires the investigation of these materials under different operating situations. In the optimal design of the absorbers, it is essential to know how the dynamical properties of the viscoelastic materials change with temperature. In a previous work, the authors presented a methodology to optimally design a linear viscoelastic dynamic vibration absorber to be attached to a cubic nonlinear single-degree-of-freedom system, in a given temperature. In the present work, a study of how temperature variations affect the optimal design of two viscoelastic absorbers, made of distinct materials (neoprene and butyl rubber), is addressed. The mathematical formulation of the problem is based on the concept of generalized equivalent parameters and the harmonic balance method is employed in the solution stage. A cubic nonlinearity in the primary system is considered and the four parameter fractional derivative model of viscoelastic materials is used. Numerical simulations are performed using a recursive equation, in order to find the new characteristics of the absorbers at different working temperatures. The results show that the answer depends not only on the temperature and the material, but also on the magnitude of the excitation load imposed to the system. For a low magnitude of the excitation load, it is verified that the neoprene absorber is less affected by a temperature variation, in terms of its vibration control capabilities. On the other hand, a large magnitude of the load can significantly affect the performance of both considered devices when the working temperature is different from the design temperature.
Low speed bearings fault detection and size estimation using instantaneous angular speed
Authors: Moustafa W , Cousinard O , Bolaers F , Sghir K , Dron JP
Published: November 2014

The fault diagnosis and prognosis of low speed machines remains a difficult problem despite remarkable advances in the conditional monitoring domain. The Rolling-element bearing is a vital part of these machines and its failure is one of the main causes of machine breakdown. In order to have an efficient maintenance strategy, fault diagnosis of a bearing and time estimation of its remaining useful life is needed. However, conventional vibration analysis at very low speeds generally fails to detect vibrations issued from a faulty bearing due to its low energy, high and variable loading conditions and to the noisy environment generated by other mechanical components of low speed machines such as gearing systems. In this work, instantaneous angular speed (IAS)-based fault diagnosis is introduced in order to compensate for the shortcoming of conventional monitoring techniques since it is strictly synchronized to shaft rotation and much less dependent on the transfer path between the defect and the sensor contrary to vibration and acoustic emission analysis. At very low speeds and in the case of a seeded spall on the bearing’s race, the shaft IAS reveals the shaft dynamical behavior when the rolling element passes into the spall. It is proven that this behavior is different when entering the spall than when exiting. The determination of entrance and exit moments allows a precise fault size estimation which is a critical step for bearing prognosis. The proposed fault size estimation method is tested on different seeded spall widths at different low speeds. The results gave a satisfactory fault width estimation and show that IAS measurement is a promising tool for the health monitoring of very low speed machines.
Education and Coronary Heart Disease Risk
Authors: Loucks Eric B. , Gilman Stephen E. , Howe Chanelle J. , Kawachi Ichiro , Kubzansky Laura D. , Rudd Rima E. , Martin Laurie T. , Nandi Arijit , Wilhelm Aude , Buka Stephen L.
Published: November 2014

Objective. Education is inversely associated with coronary heart disease (CHD) risk; however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in the education-CHD literature explain the associations between education and CHD risk. Method. The study sample included 346 participants, aged 38 to 47 years (59.5% women), of the New England Family Study birth cohort. Ten-year CHD risk was calculated using the validated Framingham risk algorithm that utilizes diabetes, smoking, blood pressure, total cholesterol, high-density lipoprotein cholesterol, age, and gender. Multivariable regression and mediation analyses were performed. Results. Regression analyses adjusting for age, race/ethnicity, and childhood confounders (e.g., parental socioeconomic status, intelligence) demonstrated that relative to those with greater than or equal to college education, men and women with less than high school had 73.7% (95% confidence interval [CI; 29.5, 133.0]) and 48.2% (95% CI [17.5, 86.8]) higher 10-year CHD risk, respectively. Mediation analyses demonstrated significant indirect effects for reading comprehension in women (7.2%; 95% CI [0.7, 19.4]) and men (7.2%; 95% CI [0.8, 19.1]), and depressive symptoms (11.8%; 95% CI [2.5, 26.6]) and perceived constraint (6.7%, 95% CI [0.7, 19.1]) in women. Conclusions. Evidence suggested that reading comprehension in women and men, and depressive symptoms and perceived constraint in women, may mediate some of the association between education and CHD risk. If these mediated effects are interpreted causally, interventions targeting reading, depressive symptoms, and perceived constraint could reduce educational inequalities in CHD.
Young people with features of gender dysphoria: Demographics and associated difficulties
Authors: Holt Vicky , Skagerberg Elin , Dunsford Michael
Published: November 2014

This article presents the findings from a cross-sectional study on demographic variables and associated difficulties in 218 children and adolescents (Mean age = 14 years, SD = 3.08, range = 5–17 years), with features of gender dysphoria, referred to the Gender Identity Development Service (GIDS) in London during a 1-year period (1 January 2012–31 December 2012). Data were extracted from patient files (i.e. referral letters, clinical notes and clinician reports). The most commonly reported associated difficulties were bullying, low mood/depression and self-harming. There was a gender difference on some of the associated difficulties with reports of self-harm being significantly more common in the natal females and autism spectrum conditions being significantly more common in the natal males. The findings also showed that many of the difficulties increased with age. Findings regarding demographic variables, gender dysphoria, sexual orientation and family features are reported, and limitations and implications of the cross-sectional study are discussed. In conclusion, young people with gender dysphoria often present with a wide range of associated difficulties which clinicians need to take into account, and our article highlights the often complex presentations of these young people.
Getting Norway to eat healthier: What are the opportunities?
Authors: Oostindjer Marije , Amdam Gro V , Egelandsdal Bjørg
Published: November 2014

Aim: Increased food consumption and the related problem of obesity have spurred initiatives to motivate consumers to eat healthier. Some strategies have shown positive but only short-term effects, as consumers or other stakeholders do not accept them sufficiently in the long term. The aim of this study was to investigate opportunities for healthier eating in Norway according to both consumers and other stakeholders. Methods: Five focus-group sessions were conducted with individuals working in the food industry, retail, public health, research and various non-governmental organisations related to food consumption. Topics that were discussed in the focus groups were transformed into a consumer survey, which was conducted with 1178 respondents. Results: The focus groups often indicated a specific responsibility for the food industry to get people to eat healthier. Survey respondents indicated that all actors in the food chain had responsibility for healthier eating in the population, but agreed that the food industry, as well as the health authority, have major responsibilities. Food education was regarded as a favourable strategy in the focus groups and by survey respondents to help people to eat healthier, as were less advertising of unhealthy food and developing new healthy food products. Such strategies should be focused on parents, families, schools and children according to both focus group and survey participants. Implementation challenges include consumers wanting freedom to choose what they eat and consumers wanting food information that is easier to understand. Conclusions: This study showed that consumers and other stakeholders see opportunities for healthier eating in Norway by providing more food education and clearer food information, targeted towards children, families and parents.
Variable selection in joint modelling of the mean and variance for hierarchical data
Authors: Charalambous Christiana , Pan Jianxin , Tranmer Mark
Published: November 2014

We propose to extend the use of penalized likelihood variable selection to hierarchical generalized linear models (HGLMs) for jointly modelling the mean and variance structures. We assume a two-level hierarchical data structure, with subjects nested within groups. A generalized linear mixed model (GLMM) is fitted for the mean, with a structured dispersion in the form of a generalized linear model (GLM) for the between-group variation. To do variable selection, we use the smoothly clipped absolute deviation (SCAD) penalty, which simultaneously shrinks the coefficients of redundant variables to 0 and estimates the coefficients of the remaining important covariates. We run simulation studies and real data analysis for the joint mean–variance models, to assess the performance of the proposed procedure against a similar process which excludes variable selection. The results indicate that our method can successfully identify the zero/non-zero components in our models and can also significantly improve the efficiency of the resulting penalized estimates.
Regression with compositional response having unobserved components or below detection limit values
Authors: van den Boogaart Karl Gerald , Tolosana-Delgado Raimon , Templ Matthias
Published: November 2014

The typical way to deal with zeros and missing values in compositional data sets is to impute them with a reasonable value, and then the desired statistical model is estimated with the imputed data set, e.g., a regression model. This contribution aims at presenting alternative approaches to this problem within the framework of Bayesian regression with a compositional response. In the first step, a compositional data set with missing data is considered to follow a normal distribution on the simplex, which mean value is given as an Aitchison affine linear combination of some fully observed explanatory variables. Both the coefficients of this linear combination and the missing values can be estimated with standard Gibbs sampling techniques. In the second step, a normally distributed additive error is considered superimposed on the compositional response, and values are taken as ‘below the detection limit’ (BDL) if they are ‘too small’ in comparison with the additive standard deviation of each variable. Within this framework, the regression parameters and all missing values (including BDL) can be estimated with a Metropolis-Hastings algorithm. Both methods estimate the regression coefficients without need of any preliminary imputation step, and adequately propagate the uncertainty derived from the fact that the missing values and BDL are not actually observed, something imputation methods cannot achieve.
Habits, style and how to wear them lightly
Authors: Hynes Maria , Sharpe Scott
Published: November 2014

Contributing to cultural geography’s emerging interest in the work of Felix Ravaisson, this article explores the relationship between the impersonal force of habit and the personalised production of subjectivity. More precisely, our concern is with the relationship between habit and the stylisation of self that can be witnessed in the production of the intellectual subject. Paying particular attention to the relationship he traces between habit, consciousness and the effort that defines subjectivity, we explore the implications of Ravaisson’s understanding of habit for the work of style, understood as an integration of habits and dispositions into a manner of being. By exploring the question of intellectual style in the work of Alain Badiou, Michel Foucault and Friedrich Nietzsche, we consider what the implications might be of performing that task of integration lightly, without the lofty weightiness that often attends intellectual life.
Internationally minded schools as cultural artefacts: Implications for school leadership
Authors: Hill Ian
Published: November 2014

This article adopts a non-rational, existential, subjective approach to school leadership, on the assumption that rational models provide useful pointers on mechanics such as time management, coaching and staff evaluation, but are less appropriate for grasping the essence of leadership which resides in managing interpersonal relationships and the individual interpretation of reality. A view of internationally minded schools as complex cultural artefacts is explored with reference to scholars of organisation theory and cultural dimensions. Schools are a repository of societal cultures which the leadership attempts to weave into a cohesive tapestry of educational vision and commitment, and this, in turn, becomes the organisational culture. Implications for leadership awareness and behaviour stemming from this perspective are that there are no fixed ways of construing social reality, artistic and literary images are helpful for unravelling social reality, and reflection on whether social reality is individually or collectively defined. The article concludes with discussion of an appropriate style for successfully leading internationally minded schools conceived as cultural artefacts.
Affective ambiences created with lighting for older people
Authors: Kuijsters A , Redi J , de Ruyter B , Seuntiëns P , Heynderickx I
Published: November 2014

Current lighting technologies provide huge flexibility in creating ambiences that may be adapted to the needs of an occupant in a room. These ambiences not only satisfy visual needs, but may also improve people’s well-being. This paper describes one possible application of adaptable light ambiences, namely to counteract negative mood states that older people often experience in care centres. To this end, we wanted to create a pleasant, relaxing ambience to counteract anxiousness and a pleasant, activating ambience to counteract sadness. We asked 15 (relatively young) lighting designers to create these ambiences and averaged their input to create both ambiences in a real room. Subsequently, these ambiences were evaluated with the Atmosphere questionnaire by younger and older participants. The affective connotation of the ambiences in terms of the Atmosphere dimensions was well recognized by the younger participants but significantly less so by the older people. Hence, a photo interview with older people was used to make the ambiences more appropriate for them. A final validation experiment confirmed that the affective connotation of these new ambiences was well recognized by the older people.
Persistent endoleak after endovascular aneurysm repair for acute Q-fever-infected aortocaval fistula
Authors: Prinsen Jan-Hein S , Boersma Doeke , van Loenhout Ruud , van Schaik Paul M , Verhoeven Bart AN
Published: November 2014

We present a case of an endovascular aneurysm repair for a Q-fever-infected acute abdominal aortic aneurysm with aortocaval fistula. Type 2 endoleak persisted after successful endovascular repair.
Towards a model of the perceived value of innovation: The key role of perceived benefits ahead of the adoption process
Authors: Rivière Arnaud
Published: November 2014

To better understand consumer behavior in the early stages of interaction with a new product, a theoretical model of perceived value formation for an innovation is proposed and tested. The quantitative study, conducted in the automobile sector on a sample of 828 consumers, demonstrates that the perceived value of a new product is influenced ahead of the adoption process by its perceived benefits but not by its perceived sacrifices. Similarly, individual variables do not directly influence the perceived value of the new product, but only its perceived attributes.
A Structural Equation Model for Measuring the Impact of Employee Retention Practices on Employee’s Turnover Intentions: An Indian Perspective
Authors: Kashyap Vaneet , Rangnekar Santosh
Published: November 2014

The role of human resource management practices dealing with employee turnover has been widely explored and examined in the existing literature. The majority of human resource management researchers have focused on the role of policies and practices in different sectors related to employee retention. However, less attention has been given to identify the practices and policies common across all industries and sectors. The present study attempts to identify and examine the most important practices of employee retention management and proposes a comprehensive structural equation model to measure the impact of these practices on employee’s turnover intentions. After an extensive review of literature, compensation, job characteristics, training, career opportunities and work–life balance have been identified as five important practices dealing with employee turnover and are common across all industries. These practices constitute the component factors of an employee retention management predicting employee’s turnover intentions. A five-factor scale with a 33-item measurement model has been validated in the study. Theoretical and managerial implications are discussed in the light of the findings.
Aligning Learning & Development Strategy with Business: Strategy to Operations
Authors: Panda Abinash , Karve Swati , Mohapatra Dilip
Published: November 2014

This research note presents the current challenges for the learning leaders in India, and what they should do to ensure that learning function is treated as a strategic function by the business leaders. The need is to align learning function with the business, assessing the current level of organizational capabilities vis-à-vis what is needed now and in the future to remain competitive. Such assessment helps to identify the capability gaps, which should be bridged through developmental interventions, conceptualized and executed by the Learning & Development function. Execution is vital for this as most often well-crafted strategy goes awry, if not properly executed. A template to operationalize Learning & Development strategy is also discussed in this article.
Interaction between asthma and smoking increases the risk of adult airway obstruction
Authors: Aanerud Marianne , Carsin Anne-Elie , Sunyer Jordi , Dratva Julia , Gislason Thorarinn , Jarvis Deborah , deMarco Roberto , Raherison Chantal , Wjst Matthias , Dharmage Shyamali C. , Svanes Cecilie
Published: November 2014

The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy.

In the European Community Respiratory Health Survey, 15 668 persons aged 20–56 years underwent spirometry in 1991–1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI).

A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never-smokers: OR 21.0, 95% CI 12.7–35; current smokers: OR 23.7, 95% CI 13.9–40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6–41.9) than among never-smokers (OR 11.2, 95% CI 6.8–18.6) (RERI 12.02, 95% CI 1.96–22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics.

Early- and late-onset asthma were associated with 10–20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed.
Novel drugs against tuberculosis: a clinician's perspective
Authors: Olaru Ioana Diana , von Groote-Bidlingmaier Florian , Heyckendorf Jan , Yew Wing Wai , Lange Christoph , Chang Kwok Chiu
Published: November 2014

The United Nations Millennium Development Goal of reversing the global spread of tuberculosis by 2015 has been offset by the rampant re-emergence of drug-resistant tuberculosis, in particular fluoroquinolone-resistant multidrug-resistant and extensively drug-resistant tuberculosis. After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials. Before novel drugs can find their place in the battle against drug-resistant tuberculosis, linezolid has been compassionately used with success in the treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis. This review largely discusses six novel drugs that have been evaluated in phase II and III clinical trials, with focus on the clinical evidence for efficacy and safety, potential drug interactions, and prospect for using multiple novel drugs in new regimens.
On common α-fuzzy fixed points with applications
Authors: Latif Abdul , Roldán-López-de-Hierro Antonio-Francisco , Sintunaravat Wutiphol
Published: November 2014

In this paper, we introduce a notion of α-continuity of fuzzy mappings and some generalized contractive conditions for α-level sets. Then we prove some theorems on the existence of common α-fuzzy fixed points for a pair of fuzzy mappings. Consequently, we obtain some results on metric spaces endowed with binary relations, and graphs. Further, using α-fuzzy fixed point techniques we obtain common fixed point results for multi-valued mappings on metric spaces.
Sphingosine 1-Phosphate to p38 Signaling via S1P1 Receptor and Gαi/o Evokes Augmentation of Capsaicin-Induced Ionic Currents in Mouse Sensory Neurons
Authors: Langeslag Michiel , Quarta Serena , Leitner Michael G , Kress Michaela , Mair Norbert
Published: November 2014

The perception of painful thermal stimuli by sensory neurons is largely mediated by TRPV1. Upon tissue injury or inflammation, S1P is secreted by thrombocytes as part of an inflammatory cocktail, which sensitizes nociceptive neurons towards thermal stimuli. S1P acts on G-protein coupled receptors that are expressed in sensory neurons and sensitize TRPV1 channels towards thermal stimuli. In this study, the S1P mediated signaling pathway required for sensitization of TRPV1 channels was explored.

The capsaicin induced peak inward current (Icaps) of sensory neurons was significantly increased after S1P stimulation within minutes after application. The potentiation of ICAPS resulted from activation of Gαi through G-protein coupled receptors for S1P. Consequently, Gαi led to a signaling cascade, involving phosphoinositide-3-kinase (PI3K) and protein kinase C, which augmented ICAPS in nociceptive neurons. The S1P1 receptor agonist SEW2871 resulted in activation of the same signaling pathway and potentiation of ICAPS. Furthermore, the mitogen-activated protein kinase p38 was phosphorylated after S1P stimulation and inhibition of p38 signaling by SB203580 prevented the S1P-induced ICAPS potentiation. The current data suggest that S1P sensitized ICAPS through G-protein coupled S1P1 receptor activation of Gαi-PI3K-PKC-p38 signaling pathway in sensory neurons.
Evaluation of proliferation and apoptosis markers in circulating tumor cells of women with early breast cancer who are candidates for tumor dormancy
Authors: Spiliotaki Maria , Mavroudis Dimitris , Kapranou Kyriaki , Markomanolaki Harris , Kallergi Galatea , Koinis Filippos , Kalbakis Kostas , Georgoulias Vassilis , Agelaki Sofia
Published: November 2014

Introduction

Clinical dormancy is frequently observed in breast cancer. In the present study, we aimed to characterize circulating tumor cells (CTCs) in dormancy candidates (DC) with early breast cancer in terms of proliferation and apoptosis.

Methods

Cytospins of peripheral blood mononuclear cells (PBMCs) were obtained from DC (n = 122) who were disease-free for at least 5 years and from metastatic patients (n = 40) who relapsed more than 5 years after surgery. Sequential samples from eight DC (n = 36) who maintained a prolonged disease-free status and from eight DC (n = 27) presenting late relapse during follow-up, were also analyzed. PBMCs were triple stained with a pancytokeratin, antibody along with anti-Ki67 and anti-M30 antibodies as proliferation and apoptosis markers, respectively.

Results

CTCs were identified in 40 (33%) of 122 DC and in 15 (37.5%) of 40 metastatic patients. In total, twenty-five (62.5%) DC had exclusively dormant (Ki67(-)/M30(-)), seven (17.5%) had proliferative Ki67(+)/M30(-), four (10%) had apoptotic Ki67(-)/M30(+) and four (10%) had both phenotypes of proliferative and apoptotic CTCs. In comparison, 53.4% of CTC-positive metastatic patients had exclusively dormant and 46.6% had proliferative CTCs; none had apoptotic CTCs (P = 0.039). Among all CTCs detected in DC patients, 82.4% were dormant, whereas in the nondormant population, 32.5% were proliferative and 67.5% apoptotic. The respective percentages in metastatic patients were 59.1%, 100% and 0% (P <0.0001). Moreover, apoptotic CTCs prevailed among nondormant CTCs detected in sequential samples from DC who remained in a prolonged disease-free status compared to those presenting late relapse during follow-up (70.6% versus 43.5% (P = 0.0002)).

Conclusions

The apoptotic index of CTCs is increased during clinical dormancy, whereas the proliferation index is increased on relapse. In addition, apoptotic CTCs are more frequently encountered during follow-up in DC patients who remain disease-free compared to those with subsequent late relapse, suggesting that monitoring proliferation and apoptosis in CTCs during clinical dormancy merits further investigation as a tool for predicting late disease recurrence.
Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer
Authors: García-Martínez Elena , Gil Ginés Luengo , Benito Asunción Chaves , González-Billalabeitia Enrique , Conesa María Angeles Vicente , García Teresa García , García-Garre Elisa , Vicente Vicente , de la Peña Francisco Ayala
Published: November 2014

Introduction

Tumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear.

Methods

We analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival.

Results

We identified three tumor-infiltrating immune cell profiles, which were able to predict pathological complete response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor identified a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival.

Conclusions

Breast cancer immune cell subpopulation profiles, determined by immunohistochemistry-based computerized analysis, identify groups of patients characterized by high response (in the pre-treatment setting) and poor prognosis (in the post-treatment setting). Further understanding of the mechanisms underlying the distribution of immune cells and their changes after chemotherapy may contribute to the development of new immune-targeted therapies for breast cancer.
Plasmodium falciparumgene expression measured directly from tissue during human infection
Authors: Van Tyne Daria , Tan Yan , Daily Johanna P , Kamiza Steve , Seydel Karl , Taylor Terrie , Mesirov Jill P , Wirth Dyann F , Milner Danny A
Published: November 2014

Background

During the latter half of the natural 48-h intraerythrocytic life cycle of human Plasmodium falciparum infection, parasites sequester deep in endothelium of tissues, away from the spleen and inaccessible to peripheral blood. These late-stage parasites may cause tissue damage and likely contribute to clinical disease, and a more complete understanding of their biology is needed. Because these life cycle stages are not easily sampled due to deep tissue sequestration, measuring in vivo gene expression of parasites in the trophozoite and schizont stages has been a challenge.

Methods

We developed a custom nCounter® gene expression platform and used this platform to measure malaria parasite gene expression profiles in vitro and in vivo. We also used imputation to generate global transcriptional profiles and assessed differential gene expression between parasites growing in vitro and those recovered from malaria-infected patient tissues collected at autopsy.

Results

We demonstrate, for the first time, global transcriptional expression profiles from in vivo malaria parasites sequestered in human tissues. We found that parasite physiology can be correlated with in vitro data from an existing life cycle data set, and that parasites in sequestered tissues show an expected schizont-like transcriptional profile, which is conserved across tissues from the same patient. Imputation based on 60 landmark genes generated global transcriptional profiles that were highly correlated with genome-wide expression patterns from the same samples measured by microarray. Finally, differential expression revealed a limited set of in vivo upregulated transcripts, which may indicate unique parasite genes involved in human clinical infections.

Conclusions

Our study highlights the utility of a custom nCounter® P. falciparum probe set, validation of imputation within Plasmodium species, and documentation of in vivo schizont-stage expression patterns from human tissues.
Quantitative neuropathological assessment to investigate cerebral multi-morbidity
Authors: Attems Johannes , Neltner Janna H , Nelson Peter T
Published: November 2014

The aging brain is characterized by the simultaneous presence of multiple pathologies, and the prevalence of cerebral multi-morbidity increases with age. To understand the impact of each subtype of pathology and the combined effects of cerebral multi-morbidity on clinical signs and symptoms, large clinico-pathological correlative studies have been performed. However, such studies are often based on semi-quantitative assessment of neuropathological hallmark lesions. Here, we discuss some of the new methods for high-throughput quantitative neuropathological assessment. These methods combine increased quantitative rigor with the added technical capacity of computers and networked analyses. There are abundant new opportunities - with specific techniques that include slide scanners, automated microscopes, and tissue microarrays - and also potential pitfalls. We conclude that quantitative and digital neuropathologic approaches will be key resources to further elucidate cerebral multi-morbidity in the aged brain and also hold the potential for changing routine neuropathologic diagnoses.
Alteration in brain-derived neurotrophic factor (BDNF) after treatment of mice with herbal mixture containing Euphoria longana, Houttuynia cordata and Dioscorea japonica
Authors: Jeon Songhee , Lee Chia-Hung , Liu Quan Feng , Kim Geun Woo , Koo Byung-Soo , Pak Sok Cheon
Published: November 2014

Background

Literature data indicate that brain-derived neurotrophic factor (BDNF), cyclic-AMP response element-binding protein (CREB) and phospho-CREB (pCREB) may have a place in depression. BDNF belongs to the neurotrophin family that plays an important role in proliferation, survival and differentiation of different cell populations in the mammalian nervous system. The herbal mixture used in the present study consists of Euphoria longana, Houttuynia cordata and Dioscorea japonica. The purpose of the present study was to determine the neuroprotective effect of herbal mixture. We also tested the hypothesis that administration of herbs reverses memory deficits and promotes the protein expression of BDNF in the mouse brain.

Methods

Mice were randomized into four different treatment groups (n = 10/group). Normal and stress groups received regular lab chow without stress and under stress conditions, respectively, for 3 weeks. The animals in the stress group were immobilized for 4 hours a day for 2 weeks. Different doses of herbal mixture (206 and 618 mg/kg) were administered for 3 weeks to those mice under stress conditions. Mice were analyzed by behavioral tests and immunoblotting examination in the hippocampus and cortex. An additional in vitro investigation was performed to examine whether herbs induce neurotoxicity in a human neuroblastoma cell line, SH-SY5Y cells.

Results

No significant toxicity of herbs on human neuroblastoma cells was observed. These herbs demonstrated an inductive effect on the expression of BDNF, pCREB and pAkt. For spatial working memory test, herbal mixture fed mice exhibited an increased level of spontaneous alternation (p < 0.01) compared to those in stress conditions. Moreover, herbal mixture produced highly significant (p < 0.01) reduction in the immobility time in the tail suspension test. Mice in the herbal mixture groups demonstrated lower serum corticosterone concentration than mice in the stress group (p < 0.05). Effects of the oral administration of herbal mixture on protein levels of BDNF in the hippocampi and cortices were significant.

Conclusions

Our study showed that herbal mixture administration has antidepressant effects in mice. It is proposed that adverse events such as stress and depression can modulate the expression of molecular players of cellular plasticity in the brain.
Gross morphological brain changes with chronic, heavy cannabis
use
Authors: Lorenzetti Valentina , Solowij Nadia , Whittle Sarah , Fornito Alex , Lubman Dan I. , Pantelis Christos , Yücel Murat
Published: November 2014

We investigated the morphology of multiple brain regions in a rare sample of
15 very heavy cannabis users with minimal psychiatric comorbidity or
significant exposure to other substances (compared with 15 age- and
IQ-matched non-cannabis-using controls) using manual techniques. Heavy
cannabis users demonstrated smaller hippocampus and amygdala volumes, but no
alterations of the orbitofrontal and anterior- and paracingulate cortices,
or the pituitary gland. These findings indicate that chronic cannabis use
has a selective and detrimental impact on the morphology of the
mediotemporal lobe.
Cisplatin and Etoposide Versus Carboplatin and Paclitaxel With Concurrent Radiotherapy for Stage III Non–Small-Cell Lung Cancer: An Analysis of Veterans Health Administration Data
Authors: Santana-Davila Rafael , Devisetty Kiran , Szabo Aniko , Sparapani Rodney , Arce-Lara Carlos , Gore Elizabeth M. , Moran Amy , Williams Christina D. , Kelley Michael J. , Whittle Jeffrey
Published: November 2014

Purpose

The optimal chemotherapy regimen to use with radiotherapy in stage III non–small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP).

Methods

We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data.

Results

A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). In an instrumental variables analysis, there was no survival advantage for patients treated in centers where EP was used more than 50% of the time as compared with centers where EP was used in less than 10% of the patients (HR, 1.07; 95% CI, 0.90 to 1.26). Patients treated with EP, compared with patients treated with CP, had more hospitalizations (2.4 v 1.7 hospitalizations, respectively; P < .001), outpatient visits (17.6 v 12.6 visits, respectively; P < .001), infectious complications (47.3% v 39.4%, respectively; P = .0022), acute kidney disease/dehydration (30.5% v 21.2%, respectively; P < .001), and mucositis/esophagitis (18.6% v 14.4%, respectively; P = .0246).

Conclusion

After accounting for prognostic variables, patients treated with EP versus CP had similar overall survival, but EP was associated with increased morbidity.
Leiomodin 3 and Tropomodulin 4 have overlapping functions during skeletal myofibrillogenesis
Authors: Nworu Chinedu U. , Kraft Robert , Schnurr Daniel C. , Gregorio Carol C. , Krieg Paul A.
Published: November 2014

Precise regulation of thin filament length is essential for optimal force generation during muscle contraction. The thin filament capping protein tropomodulin (Tmod) contributes to thin filament length uniformity by regulating elongation and depolymerization at thin filament ends. The Leiomodins (Lmods 1–3) are structurally related to the Tmods 1–4 and also localize to actin filament pointed ends, but in vitro biochemical studies indicate that Lmods act instead as robust nucleators. Here we examined the roles of Tmod4 and Lmod3 during Xenopus skeletal myofibrillogenesis. Loss of Tmod4 or Lmod3 resulted in severe disruption of sarcomere assembly and impaired embryonic movement. Remarkably, when Tmod4 deficient embryos were supplemented with additional Lmod3, and Lmod3 deficient embryos were supplemented with additional Tmod4, sarcomere assembly was rescued and embryonic locomotion improved. These results demonstrate for the first time that appropriate levels of both Tmod4 and Lmod3 are required for embryonic myofibrillogenesis and unexpectedly, both proteins can share redundant functions during in vivo skeletal muscle thin filament assembly. Further, these studies demonstrate the value of Xenopus for analysis of contractile protein function during de novo myofibril assembly.