bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear covariance techniques for closed-loop guidance navigation and control system design and analysis
Authors: Christensen Randall S , Geller David
Published: December 2012

While linear covariance analysis is widely used for navigation system design and analysis, it is often overlooked as a tool for closed-loop guidance navigation and control (GN&C) system design and analysis. This article presents an overview of the techniques and methods required to develop a linear covariance analysis tool for a close-loop GN&C system. Then, using a simple nonlinear closed-loop GN&C problem as a guide, the capabilities of linear covariance analysis for the design and analysis of closed-loop systems are demonstrated. It is shown that linear covariance can be accurately applied to a closed-loop system with time-to-go guidance, dead-reckoning navigation, and a Kalman filter for state estimation. The accuracy and efficiency of linear covariance analysis is shown by direct comparison to Monte Carlo analysis results, and the value of linear covariance analysis is highlighted by presenting several analysis capabilities that are often required in the design and analysis of closed-loop GN&C systems. It is also shown how the efficiency of linear covariance enables new design methodologies, one of which is presented in this article, that would otherwise be prohibitive with Monte Carlo analysis.
Are Chinese women turning sharp-tongued?
Authors: Zhang Wei , Kramarae Cheris
Published: December 2012

What are the preferred styles of women’s talk among young Chinese, who, at least in urban China, spend much time interacting online? Using controversial episodes from a popular matchmaking show in China as the basis of discussion, we invited college students to participate in three synchronous online focus groups to discuss issues related to women’s talk in contemporary China. We identified five major themes associated with their observations and notions about women’s talk in everyday life: sharp talk, humor, lady talk, baby talk, and cursing. We observed that changing ideologies and internal tensions and inconsistencies among governments, media, and citizens mean that expectations for women’s talk are not a constant, but are always tied to historical changes and challenges. At a methodological level, we suggest that the creative use of new communication technologies can provide a more familiar and practical way of asking and answering questions about language and gender.
The hegemony of inclusion: A corpus-based critical discourse analysis of deixis in education policy
Authors: Mulderrig Jane
Published: December 2012

This article presents findings from a critical historical analysis of UK education policy discourse from 1972 onwards. It argues that the pronoun we was introduced as an important rhetorical tool by which New Labour was able to legitimate its policy decisions through the idea of a neoliberal ‘consensus’ on the context of education, while at the same time articulating a ‘politics of inclusion’. The study combined a corpus-aided approach to critical discourse analysis with political economic theory in order to interpret the data in relation to its historical context of a profound rethink of the relationship between education, the state and the economy. The analysis reveals how the flexible semantics of person deixis are exploited in a highly systematic way so as to claim consensus over politically contestable claims.
Racism in the global era: Analysis of Korean media discourse around migrants, 1990–2009
Authors: Kim Sookyung
Published: December 2012

Racism has taken on subtle forms that are hard to notice unless given careful attention. In the era of globalization, interpreting racism becomes more complicated in that globalization intensifies both racist and anti-racist reactions. This article examines how racism in the global age has evolved into a subtler form. Using both frame analysis and critical discourse analysis, I examine the Korean media’s discourse around migrants in the past two decades (1990–2009). Findings show that the dominant attitude taken by the Korean media toward migrants has been positive, which is counter-intuitive considering Korea’s notorious ethnocentrism. However, a critical discursive approach reveals that these positive discourses have a variety of effects: they ironically ‘victimize’ and ‘objectify’ migrants, overlook the question of how to empower migrants, and reveal misunderstandings over what it means to embrace diversity. I conclude that in Korea, where the tension between globalization and nationalism is intense, racial prejudice becomes more disguised under the cliché of political correctness, such as the rhetoric of multiculturalism and diversity.
Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus
Authors: Wallace DJ , Navarra S , Petri MA , Gallacher A , Thomas M , Furie R , Levy RA , van Vollenhoven RF , Cooper S , Zhong ZJ , Freimuth W , Cervera R ,   for the BLISS-52 and -76, and LBSL02 Study Groups
Published: December 2012

Safety data were pooled and analyzed from one phase 2 and two phase 3 double-blind, placebo-controlled, repeat-dose systemic lupus erythematosus (SLE) trials of belimumab 1, 4 (phase 2 only), and 10 mg/kg. Types and rates of adverse events (AEs) were similar across treatment groups. Rates of patients experiencing any serious AE were 16.6%, 19.5%, 13.5%, and 18.0% with placebo, and belimumab 1, 4, and 10 mg/kg, respectively; rates of serious infusion reactions (including hypersensitivity reactions) occurring on the same days as infusions were 0.4%, 0.9%, 0%, and 0.9%, and rates of serious infections were 5.5%, 7.1%, 6.3%, and 5.3%. Malignancy rates/100 patient-years (excluding non-melanoma skin cancer) were 0.29 with placebo vs. 0.20 with all belimumab doses combined; mortality rates/100 patient-years were 0.43 vs. 0.73. These data support the conclusion that belimumab in combination with standard SLE therapy was generally well tolerated in a predominantly autoantibody-positive population with active SLE. ClinicalTrials.gov identifiers: LBSL02: NCT00071487; BLISS-52: NCT00424476; BLISS-76: NCT00410384.
Resilience as an Underexplored Outcome of Workplace Bullying
Authors: van Heugten Kate
Published: December 2012

The problem of workplace bullying appears to be especially common in the hospitality industry and in health, education, and social services. Bullying results in negative effects on the psychological and physical health and well-being of targets, bystanders, and those accused of bullying. I undertook a qualitative research project to investigate the experiences of 17 New Zealand social workers who identified themselves as having been targets of workplace bullying. All participants had experienced negative physical and psychological health impacts. I also found, however, that in the aftermath of their difficult experiences, most considered that they had eventually developed greater resilience. Resilience was enhanced when participants’ sense of control over their situation improved and when they received support from witnesses and managers. I make recommendations to indicate how these resilience-promoting conditions can be achieved in the organizational setting.
Melanosis Coli in Hyperplastic Polyps and Adenomas
Authors: Coyne John D.
Published: December 2012

Melanosis coli is a well-known occurrence in colonic biopsies. The condition is, however, reportedly absent in both neoplastic and hyperplastic colonic polyps. Herein, we describe its occurrence in 10 hyperplastic coloniuc polyps, some of which showed melanosis in adjacent biopsied mucosa, and 2 colonic adenomata.
Pseudomembranes in Rectal Prolapse
Authors: Coyne John D.
Published: December 2012

Pseudomembranes in colonic biopsies are normally associated with antibiotic related pseudomembranous colitis. Although pseudomembranes have rarely been reported in other conditions, their presence in rectal prolapse has not been previously reported.
Psychometric Properties of the French Version of the Adult Dispositional Hope Scale
Authors: Gana Kamel , Daigre Stéphanie , Ledrich Julie
Published: December 2012

In this article, we present a French adaptation and validation of the Adult Dispositional Hope Scale (ADHS). The sample was composed of 310 French adults. We found that the ADHS scores demonstrated good reliability as well as adequate temporal stability. Confirmatory factor analyses (CFA) supported a bifactorial structure of the scale. The two factors (agency and pathways) were highly correlated, but discriminant validity was established by comparing their shared variance against their average extracted variance. Multiple-group CFAs revealed evidence of configural, metric, scalar, and factorial invariance across genders. ADHS total scores as well as scores on agency and pathways were significantly and negatively related to hopelessness, negative affectivity, anxiety, and depressive mood and positively correlated with optimism and positive affect. We believe these findings show evidence for the construct validity of the ADHS.
Parallel neural network combined with sliding mode control in overhead crane control system
Authors: Lee Lun-Hui , Huang Pei-Hsiang , Shih Yu-Cheng , Chiang Tung-Chien , Chang Cheng-Yuan
Published: December 2012

A novel control for a nonlinear two-dimensional (2-D) overhead crane is proposed. Instead of the complex design procedures used in classic methods, the proposed scheme combines the principles of neural networks (NNs) and variable structure systems (VSS) to derive control signals needed to drive the cart smoothly, rapidly and with limited payload swing. The merits include the robustness and model-free properties of the sliding mode and neural based controllers, respectively. Simulations performed using a scaled 2-D mathematical model of the crane confirm the effectiveness of the proposed method.
Dynamic response of functionally graded beams under moving heat source
Authors: Malekzadeh Parviz , Shojaee Amir
Published: December 2012

As a first endeavor, the dynamic response of functionally graded (FG) beams under a moving heat source is investigated. The material properties are assumed to be temperature-dependent and graded in the thickness direction. A two-dimensional finite element method (FEM) is employed to obtain the temperature distribution throughout the beam. Then, the effect of a two-dimensional variation of temperature on the dynamic response of an FG beam with arbitrary boundary conditions is formulated based on the first-order shear deformation beam theory (FSDBT). The resulting equations of motion are transformed into a system of algebraic equation by employing the FEM in conjunction with Newmark’s time integration scheme. In order to validate the formulation and method of solution, the exact solution is achieved in the case of isotropic beams with simply supported boundary conditions. It is shown that good agreement exists between the presented approach and the exact solution. Finally, the effect of different parameters on the dynamic response of FG beams under moving heat source is studied.
The Trend in Morning Levels of Salivary Cortisol in Children With ADHD During 6 Months of Methylphenidate Treatment
Authors: Wang Liang-Jen , Huang Yu-Shu , Hsiao Cheng-Cheng , Chen Chih-Ken
Published: December 2012

Objective: To determine the trend in cortisol levels in children with ADHD treated with methylphenidate (MPH) and nontreated healthy controls over a 6-month period. Method: The morning salivary cortisol levels of 50 patients with ADHD (40 boys and 10 girls, mean age = 7.6 years) and 50 age- and gender-matched healthy controls were measured at baseline and at 1, 3, and 6 months from baseline. The neuropsychological performance of the ADHD patients was measured via administration of the Continuous Performance Test. Results: The cortisol levels of ADHD patients increased significantly after 1 month of MPH treatment before decreasing to an intermediate level, but were significantly positively correlated with neuropsychological performance throughout the 6-month treatment period. The cortisol levels of the controls did not change significantly over the 6-month period. Conclusion: MPH administration appears to positively influence the functioning of the hypothalamic–pituitary–adrenal axis in ADHD patients.
The Kind Nature Behind the Unsocial Semblance
Authors: Schäfer Thomas , Kraneburg Thomas
Published: December 2012

Objective: Although ADHD is largely associated with antisocial behavior, those affected are often said to show pronounced justice sensitivity. To investigate this assumption, the authors compared participants with ADHD with healthy controls. Method: An experimental game was used to investigate decisions associated with social justice. A questionnaire was used to measure four dimensions of justice sensitivity: observer, profiteer, perpetrator, and victim sensitivity. Results: Participants with ADHD produced higher values in observer and profiteer sensitivity than the control group. There were no differences in perpetrator sensitivity. Questionnaire results reveal that the inattentive subtype exhibited higher justice sensitivity than the hyperactive/impulsive and combined subtypes and the control group on all dimensions. Conclusion: The results confirm that justice sensitivity is indeed more pronounced in people with ADHD, particularly in the inattentive subtype. It is suggested that pronounced justice sensitivity may be a coping strategy for inferring appropriate social behavior.
A Trend Analysis of Participant and Setting Characteristics in Autism Intervention Research
Authors: Crosland Kimberly A. , Clarke Shelley , Dunlap Glen
Published: December 2012

The current trend analysis was conducted to empirically document the characteristics of individuals with autism who participated in intervention research published between 1995 and 2009 in three journals ( Journal of Applied Behavior Analysis, Journal of Autism and Developmental Disorders, and Focus on Autism and Other Developmental Disabilities). Information was collected on age of participants, cognitive and communicative functioning, setting, and ecological variables. Overall, the data are interpreted to document few changes over time; however, increasing trends were noted in the proportion of studies that included children below the age of 6 years and in the proportion of studies that included higher functioning participants. The data are discussed in relation to the status of intervention research and demographic changes pertaining to autism.
Deferred Imitation and Social Communication in Speaking and Nonspeaking Children With Autism
Authors: Strid Karin , Heimann Mikael , Gillberg Christopher , Smith Lars , Tjus Tomas
Published: December 2012

Deferred imitation and early social communication skills were compared among speaking and nonspeaking children with autism and children developing typically. Overall, the children with autism showed a lower frequency on measures of deferred imitation and social communication compared with typically developing children. Deferred imitation was observed at a significantly lower level among the speaking and nonspeaking groups of children with autism. However, when comparing the speaking autism group with the typical group, many differences in observed social communication disappeared. These results underscore the importance of considering children’s verbal ability in autism research and clinical practice, and indicate that there are specific difficulties in deferred imitation in autism but that the social communication deficits that are observed are greatly influenced by low level of verbal ability.
Investigation on tribological behaviour of diesel engine exhaust valve dry sliding against valve seat
Authors: Zhang Shaoyang , Jin Xuefeng , Zhong Wenwu , Xu Aijiao , Zhou Xiaoli , Ma Li , Qiu Zhanhong
Published: December 2012

A high-chromium alloy with 2Cr32Si2MnMo2 available for diesel engine valve seats was fabricated by centrifugal casting to improve valve seat quality. The friction and wear performances of the valve seat dry sliding against an exhaust valve were measured using a SRV testing machine. The test procedures include temperature and load sensitivities and wear. The test temperatures ranged from 100 ℃ to 280 ℃ and loads from 50 to 125 N. The friction and wear of the valve seat were found to decrease first and then increase with the increment of temperature or load. Scanning electron microscopy and energy dispersive X-ray spectroscopy analyses revealed the tribofilms contained more friction-increasing Cr2O3 and the wear mechanism was a complicated combination of two-body abrasion, three-body abrasion and oxidation. The strong adhesion between the valve and its seat arrested the relative sliding, but with loads going up to 150 N. In most cases, the valve had unexpectedly higher wear resistance than that of its seat over the temperature range, which is ascribed to adhesion to the tribofilms.
Health-promoting educational interventions: A one-year follow-up study
Authors: Karlqvist Lena , Gard Gunvor
Published: December 2012

Aims: The purpose of this study was to describe and analyse the effects of health-promoting educational interventions among employees in a municipality in Sweden. Methods: A randomized controlled educational intervention study was performed with 340 employees. Supervisors and workplace champions took part in two separate educational programmes with focus on health promotion. Intervention groups were teams of supervisors, teams of workplace champions and a mixed group (supervisors and workplace champions). The control group did not take part in any of the activities. Evaluations with physical fitness tests and a self-administrated questionnaire were performed twice. Focus group discussions were held. Results: All groups raised their physical fitness level from baseline to follow-up. Females in the supervisor group had increased their mean maximal oxygen uptake from 32.0 mlO2/kg*min to 34.9 mlO2/kg*min which was more than the others. Supervisors had reached increased knowledge within the area ‘organizational factors’ and behavioural changes had been obtained within the area ‘life-style’. Workplace champions working together with their supervisors had an easier and more motivated situation than workplace champions working by themselves. Conclusions: Coaching supervisors as well as the mixed group seemed to improve the intervention of health promotion most and should be continued.
All-cause mortality in relation to glycated haemoglobin in individuals with newly diagnosed type 2 diabetes: a retrospective cohort study
Authors: Khunti Kamlesh , Weston Claire , Gholap Nitin , Molokhia Mariam , Paul Sanjoy , Millett Christopher , Curcin Vasa , Majeed Azeem , Davies Melanie J
Published: December 2012

Aims:

To explore the effect of glycated haemoglobin A1C (HbA1C) on all cause mortality in individuals newly diagnosed with type 2 diabetes, with and without previous cardiovascular disease.

Methods:

We identified a total of 110,372 of individuals aged 18 to 80 years newly diagnosed with type 2 diabetes (including 9721 (8.8%) with established cardiovascular disease before diagnosis of diabetes) from the UK General Practice Research Database from 1990 to 2005. Primary outcome was all cause mortality. Cox proportional hazards models were used to assess the impact of HbA1C on survival.

Results:

Over a median follow up of 5.2 years (interquartile range 2.9 to 8.1 years) there were 20,481 deaths. The hazard ratios for all cause mortality in individuals without cardiovascular disease, using the category of 6–6.49% as reference, were 1.28 (1.08 to 1.52), 1.16 (1.00 to 1.39), 1.43 (1.20 to 1.72), 1.62 (1.35 to 1.95), 1.80 (1.52 to 2.23), and 2.43 (2.01 to 2.97) for HbA1C categories of < 6.0%, 6.50–6.99%, 7.0–7.49%, 7.5–7.99%, 8.0–8.99%, and > 9.0% respectively. In individuals with established cardiovascular disease a significant increased risk of mortality was observed for HbA1C categories above 8.00%; hazard ratios 1.91 (1.30–2.83) for HbA1C 8.00–8.99% and 1.95 (1.30–2.90) for HbA1C > 9.0%.

Conclusions:

A target of HbA1C between 6.0 and 6.5% is appropriate for individuals newly diagnosed with type 2 diabetes without cardiovascular disease. However, a target of < 8.0% may be less beneficial in individuals with established cardiovascular disease.
Determinants of Previous HIV Testing and Knowledge of Partner’s HIV Status Among Men Attending a Voluntary Counseling and Testing Clinic in Dar es Salaam, Tanzania
Authors: Conserve Donaldson , Sevilla Luis , Mbwambo Jessie , King Gary
Published: December 2012

Voluntary Counseling and Testing (VCT) remains low among men in sub-Saharan Africa. The factors associated with previous HIV testing and knowledge of partner’s HIV status are described for 9,107 men who visited the Muhimbili University College of Health Sciences’ VCT site in Dar es Salaam, Tanzania, between 1997 and 2008. Data are from intake forms administered to clients seeking VCT services. Most of the men (64.5%) had not previously been tested and 75% were unaware of their partner’s HIV status. Multivariate logistic regression revealed that age, education, condom use, and knowledge of partner’s HIV status were significant predictors of previous HIV testing. Education, number of sexual partners, and condom use were also associated with knowledge of partner’s HIV status. The low rate of VCT use among men underscores the need for more intensive initiatives to target men and remove the barriers that prevent HIV disclosure.
The Debt Crisis as Crisis of Democracy
Authors: Motha Stewart
Published: December 2012

This is a commentary on the debt crisis and its impact on the relationship between politics and the state in the US and Europe. Democratic institutions of the state face a crisis of legitimacy. They are not trusted to deliver radical transformations in the orientation of liberal capitalism. Technocrats administer austerity and ‘‘bailouts’’ while the Occupy movement generates a political momentum without consensus on what is to be demanded of law and the state. Urging engagement with the state and the necessity of hegemonic demands, this essay sketches the distinct political landscapes and trajectories in the US and Europe. It suggests that the left must engage with the European project as a significant post-national formation.
Venous thromboembolism following elbow, wrist and hand surgery: a review of the literature and prophylaxis guidelines
Authors: Roberts D. C. , Warwick D. J.
Published: December 2012

This review summarizes the literature regarding venous thromboembolism and examines the prophylaxis guidelines with relation to hand, wrist and elbow surgery. We performed an extensive literature search identifying any relevant case reports or outcome studies. Of 680 potential articles, only four contained data relevant to thrombosis after elbow, wrist and hand surgery. No isolated deep vein thromboses and only nine pulmonary embolisms were identified suggesting that the rate of venous thromboembolism is extremely low following this subset of upper limb surgery. We identified nine guidelines, of which only two (the British Society for Surgery of the Hand and the National Institute of Health and Clinical Excellence) addressed the upper limb. We present a set of recommendations based on the results of this review.
Mass Gain Behaviour of Tibial Polyethylene Inserts during Soak Testing
Authors: Brandt J-M , Charron K D J , MacDonald S J , Medley J B
Published: December 2012

Fluid adsorption and the associated mass gain behaviour in tibial inserts of total knee replacements was investigated in polyethylene (PE) manufactured from extruded GUR 1050 resin. Repeatedly removing the PE inserts from the soak fluid for gravimetric assessment (including cleaning, desiccation, and weighing) increased the mass gain. Soaking PE inserts for 46 days or 92 days seemed to give about the same mass gain. PE inserts that were soaked at 37 °C gained more mass than PE inserts soaked at room-temperature. Gas-plasma sterilized PE inserts gained less mass than gamma-in-air sterilized PE inserts. No statistically significant differences were detected in mass gain between PE inserts that were of 10 mm and 14 mm thickness. The mass gain of PE inserts was higher in protein-rich soak fluid compared with low-ion distilled water. Prior to knee simulator wear testing, tibial PE inserts should be conditioned in the same medium and under the same test conditions (gravimetric assessment frequency, fluid protein content, and fluid temperature). This approach would help improve the accuracy and precision of the gravimetrically determined PE wear rate during knee simulator wear testing.
Application of Social Cognitive Career Theory to Investigate the Effective Factors of the Career Decision-Making Intention in Iranian Agriculture Students by Using ANN
Authors: Rajabi Somayeh , Papzan Abdolhamid , Zahedi Gholamreza
Published: December 2012

The main purpose of this study was to determine the factors that affect the career decision-making intention of agriculture students of Kermanshah University based on Social Cognitive Career Theory (SCCT), by using Artificial Neural Network (ANN). The research population included agriculture students ( N = 1,122). Using stratified random sampling, a sample of 288 was constituted. Data were collected using a questionnaire, which consisted of four parts: Career Decision-Making Self-Efficacy (CDMSE), Career Decision-Making Outcome Expectation (CDMOE ), Career Exploratory Plans or Intentions (CEPI), and NEO Five Factor Inventory (NEO-FFI). Back translation was used for validity, and reliability was assessed using Cronbach’s alpha coefficient. To analyze the data, statistical methods and ANN with MATLAB software were used. On the basis of trial and error, a network, including three layers with one hidden layer with 20 neurons, Levenberg–Marquardt training algorithm, and sigmoidal transfer functions, was selected to construct the network of career decision-making intention. After training and simulation, the validation of the network was tested by linear regression ( R = .999). For assurance of the generalization, the network was tested again. Finally, analysis of variance was used to compare the network output.
The hOCT1 SNPs M420del and M408V alter imatinib uptake and M420del modifies clinical outcome in imatinib-treated chronic myeloid leukemia
Authors: Giannoudis Athina , Wang Lihui , Jorgensen Andrea L. , Xinarianos George , Davies Andrea , Pushpakom Sudeep , Liloglou Triantafilos , Zhang Jieying-Eunice , Austin Gemma , Holyoake Tessa L. , Foroni Letizia , Kottaridis Panagiotis D. , Müller Martin C. , Pirmohamed Munir , Clark Richard E.
Published: December 2012

Although the prognosis of chronic myeloid leukemia (CML) patients treated with imatinib is good, many fail to develop an optimal response or lose one. This heterogeneity could be attributed to the presence of human organic cation transporter-1 (hOCT1) single nucleotide polymorphisms (SNPs). In the present study, we analyzed the effect of 23 hOCT1 SNPs on imatinib treatment outcome in newly diagnosed CML patients using MassARRAY sequencing and pyrosequencing. The only SNP associated with outcome was M420del (rs35191146), with patients with the M420del demonstrating an increased probability of imatinib treatment failure. In CML cell lines transfected with M420del and/or M408V, M420del significantly decreased imatinib uptake, but this effect was countered if the M408V (rs628031) SNP was also present. A similar effect was seen for the uptake of the hOCT1 substrates TEA+ and ASP+. Finally, apparent hOCT1 mRNA levels were studied using both our earlier primers covering the M420del and another set that did not. Different mRNA expression was observed, explaining the disparity in published data on the prognostic importance of hOCT1 mRNA and highlighting the importance of avoiding common SNP sites in primer design. These data demonstrate that the common M420del SNP can modulate the outcome of imatinib treatment.
Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling
Authors: Bugl Stefanie , Wirths Stefan , Radsak Markus P. , Schild Hansjörg , Stein Pamela , André Maya C. , Müller Martin R. , Malenke Elke , Wiesner Tina , Märklin Melanie , Frick Julia-Stefanie , Handgretinger Rupert , Rammensee Hans-Georg , Kanz Lothar , Kopp Hans-Georg
Published: December 2012

Key Points

Steady-state and emergency granulopoiesis are both dependent on TLR signaling.
SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease
Authors: Rivat Christine , Booth Claire , Alonso-Ferrero Maria , Blundell Michael , Sebire Neil J. , Thrasher Adrian J. , Gaspar H. Bobby
Published: December 2012

Key Points

This study provides proof of concept that SAP gene transfer into HSCs can correct the multiple immune defects seen in XLP1.
Identifying persistent negative symptoms in first episode psychosis
Authors: Hovington Cindy L , Bodnar Michael , Joober Ridha , Malla Ashok K , Lepage Martin
Published: December 2012

Background

Although persistent negative symptoms (PNS) are known to contribute significantly to poor functional outcome, they remain poorly understood. We examined the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis (FEP). We also contrasted those definitions to the Proxy for the Deficit Syndrome (PDS) to identify deficit syndrome (DS) in the same FEP cohort.

Methods

One hundred and fifty-eight FEP patients were separated into PNS and non-PNS groups based on ratings from the Scale for Assessment of Negative Symptoms (SANS). PNS was defined in the following ways: 1) having a score of 3 or greater on at least 1 global subscale of the SANS (PNS_1); 2) having a score of 3 or more on at least 2 global subscales of the SANS (PNS_2); and 3) having a score of 3 or more on a combination of specific SANS subscales and items (PNS_H). For all three definitions, symptoms had to be present for a minimum of six consecutive months. Negative symptoms were measured upon entry to the program and subsequently at 1,2,3,6,9 and 12 months. Functional outcome was quantified at first assessment and month 12.

Results

PNS prevalence: PNS_1 (27%); PNS_2 (13.2%); PNS_H (13.2%). The prevalence of DS was found to be 3% when applying the PDS. Regardless of the definition being applied, when compared to non-PNS, patients in the PNS group were shown to have significantly worse functioning at month 12. All three PNS definitions showed similar associations with functional outcome at month 12.

Conclusion

Persistent negative symptoms are present in about 27% of FEP patients with both affective and non-affective psychosis. Although there has previously been doubt as to whether PNS represents a separate subdomain of negative symptoms, the current study suggests that PNS may be more applicable to FEP when compared to DS. Although all three PNS definitions were comparable in predicting functional outcome, we suggest that the PNS definition employed is dependent on the clinical or research objective at hand.
Regulation of antibiotic sales in Mexico: an analysis of printed media coverage and stakeholder participation
Authors: Dreser Anahí , Vázquez-Vélez Edna , Treviño Sandra , Wirtz Veronika J
Published: December 2012

Background

Restricting antibiotics sales to those with medical prescriptions only is a central strategy for promoting appropriate use and containing antibiotic resistance; however, many low and middle income countries have not enforced policies that prevent widespread self-medication with antibiotics. In 2010, the Mexican government announced the enforcement of antibiotic sales regulations, a policy that gained media prominence. This study analyzes media coverage of issues, stakeholder representation, and positions taken during policy agenda setting, drafting, and implementation to shed light on policy making to promote appropriate antibiotic utilization.

Methods

We carried out a quantitative content analysis of 322 newspaper articles published between January 2009 and December 2010 in 18 national and regional newspapers. Additionally, we conducted a qualitative content analysis to understand the positions adopted and strategies developed by nine key stakeholders. Framing theory guided the analysis.

Results

The Ministry of Health dominated media coverage, justifying the enforcement policy by focusing on risks of self-medication, and to a lesser degree dangers of increasing antibiotic resistance. Pharmacy associations appeared to be the leading opponents, arguing that the policy created logistical difficulties and corruption, and had negative economic impact for pharmacies and their clients. The associations developed strategies against the regulation such as attempting to delay implementation and installing physicians’ consultation offices within pharmacies. While medical associations and academic institutions called for a comprehensive strategy to combat antibiotic resistance, improve prescription quality, and create public awareness, these issues had little impact on media coverage. Consumer groups and legislators received very little media coverage.

Conclusions

The narrowly-focused and polarized media coverage ─centred on problems of self- medication and economic impact ─ was a missed opportunity to publicly discuss and to develop a comprehensive national strategy on antibiotic use in Mexico. It highlights the need for discussing and developing interventions within the framework of a pharmaceutical policy.
Application of loop-mediated isothermal amplification for malaria diagnosis during a follow-up study in São Tomé
Authors: Lee Pei-Wen , Ji Dar-Der , Liu Chia-Tai , Rampao Herodes S , do Rosario Virgilio E , Lin I-Feng , Shaio Men-Fang
Published: December 2012

Background

A reliable and simple test for the detection of malaria parasite is crucial in providing effective treatment and therapeutic follow-up, especially in malaria elimination programmes. A comparison of four methods, including nested polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) were used for the malaria diagnosis and treatment follow-up in São Tomé and Príncipe, during a successful pre-elimination campaign.

Method

During the period September to November 2009, blood samples from 128 children (five to 14 years old) with temperature ≥38°C (tympanic) in the District of Agua Grande were examined using four different methods, i.e., histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (HRP-2-RDTs), optical microscopy, nested PCR, and LAMP. First-line treatment with artesunate-amodiaquine was given for uncomplicated malaria and intravenous quinine was given for complicated malaria. Children with persistent positivity for malaria by microscopy, or either by nested PCR, or by LAMP on day 7 were given second-line treatment with artemether-lumefantrine. Treatment follow-up was made weekly, for up to four weeks.

Results

On day 0, positive results for HRP-2-RDTs, microscopy, nested PCR, and LAMP, were 68(53%), 47(37%), 64(50%), and 65(51%), respectively. When nested PCR was used as a reference standard, only LAMP was comparable; both HRP-2-RDTs and microscopy had moderate sensitivity; HRP-2-RDTs had poor positive predictive value (PPV) and a moderate negative predictive value (NPV) for the treatment follow-up. Seventy-one children with uncomplicated malaria and eight children with complicated falciparum malaria were diagnosed based on at least one positive result from the four tests as well as clinical criteria. Twelve of the 79 children receiving first-line treatment had positive results by nested PCR on day 7 (nested PCR-corrected day 7 cure rate was 85%). After the second-line treatment, nested PCR/LAMP-corrected day 28 cure rate was 83% for these 12 children.

Conclusions

HRP-2-RDTs have similar sensitivity as microscopy but less specificity. However, as compared to nested PCR, the poor sensitivity of HRP-2-RDTs indicates that low parasitaemia may not be detected after treatment, as well as the low specificity of HRP-2-RDTs indicates it cannot be applied for treatment follow-up. LAMP has similar sensitivity and specificity to nested PCR. With high PPV and NPV, LAMP is simpler and faster as compared to nested PCR with the advantage of detecting low parasitaemia becoming a potential point-of-care test for treatment follow-up.
Solvothermal synthesis, growth mechanism, and photoluminescence property of sub-micrometer PbS anisotropic structures
Authors: Cao Yali , Hu Pengfei , Jia Dianzeng
Published: December 2012

The sub-micrometer PbS with anisotropic microstructures including fishbone-like dendrites, multipods, cubes, corallines, and hopper cubes were successfully prepared by the solvothermal process. Different morphologies can be obtained by adjusting the reaction temperatures or using the nontoxic controlled reagents which can tune the relative growth rate in the <100> direction and the <111> direction of PbS nuclei. Based on the viewpoint of crystallography about face-centered cubic crystal structure, the possible formation mechanism for sub-micrometer anisotropic structures has been discussed. The difference between the enhanced growth rates on the {100} and {111} planes induced the change of ratio between the growth rates in the <100> and <111> directions, which resulted in the formation of the different PbS anisotropic microstructures. The PbS anisotropic structures exhibited the different visible emission with a peak in the red regions mainly attributed to the variation of shape, size, and the trap state of as-obtained PbS.
Validation of a model to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD: the rotterdam ischemic heart disease and stroke computer simulation (RISC) model
Authors: van Kempen Bob JH , Ferket Bart S , Hofman Albert , Steyerberg Ewout W , Colkesen Ersen B , Boekholdt S Matthijs , Wareham Nicholas J , Khaw Kay-Tee , Hunink MG Myriam
Published: December 2012

Background

We developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established.

Methods

The Rotterdam Ischemic Heart Disease and Stroke Computer Simulation (RISC) model was developed using data covering 5 years of follow-up from the Rotterdam Study. To prove 1) internal and 2) predictive validity, the incidences of coronary heart disease (CHD), stroke, CVD death, and non-CVD death simulated by the model over a 13-year period were compared with those recorded for 3,478 participants in the Rotterdam Study with at least 13 years of follow-up. 3) External validity was verified using 10 years of follow-up data from the European Prospective Investigation of Cancer (EPIC)-Norfolk study of 25,492 participants, for whom CVD and non-CVD mortality was compared.

Results

At year 5, the observed incidences (with simulated incidences in brackets) of CHD, stroke, and CVD and non-CVD mortality for the 3,478 Rotterdam Study participants were 5.30% (4.68%), 3.60% (3.23%), 4.70% (4.80%), and 7.50% (7.96%), respectively. At year 13, these percentages were 10.60% (10.91%), 9.90% (9.13%), 14.20% (15.12%), and 24.30% (23.42%). After recalibrating the model for the EPIC-Norfolk population, the 10-year observed (simulated) incidences of CVD and non-CVD mortality were 3.70% (4.95%) and 6.50% (6.29%). All observed incidences fell well within the 95% credibility intervals of the simulated incidences.

Conclusions

We have confirmed the internal, predictive, and external validity of the RISC model. These findings provide a basis for analyzing the effects of modifying cardiovascular disease risk factors on the burden of CVD with the RISC model.
Heat shock protein 70 selectively mediates the degradation of cytosolic PrPs and restores the cytosolic PrP-induced cytotoxicity via a molecular interaction
Authors: Zhang Jin , Wang Ke , Guo Yan , Shi Qi , Tian Chan , Chen Cao , Gao Chen , Zhang Bao-Yun , Dong Xiao-Ping
Published: December 2012

Background

Although the aggregation of PrPSc is thought to be crucial for the neuropathology of prion diseases, there is evidence in cultured cells and transgenic mice that neuronal death can be triggered by the accumulation of cytosolic PrPs, leading to the hypothesis that the accumulation of PrPs in the cytosol of neurons may be a primary neurotoxic culprit. Hsp70, a molecular chaperone involved in protein folding/refolding and degradation in the cytoplasm, has a protective effect in some models of neurodegenerative diseases, e.g., Alzheimer’s and Parkinson’s diseases, but its role in prion diseases remains unclear.

Results

To study the role of Hsp70 in prion diseases, we used immunoprecipitation to first identify a molecular interaction between Hsp70 and PrPs. Using immunofluorescence, we found that Hsp70 colocalized with cytosolic PrPs in HEK293 cells transiently transfected with plasmids for Cyto-PrP and PG14-PrP but not with wild-type PG5-PrP or endoplasmic reticulum (ER)-retained PrPs (3AV-PrP and ER-PrP). Using western blot analysis and apoptosis assays of cultured cells, we found that the overexpression of Hsp70 by transfection or the activation of Hsp70 by geldanamycin selectively mediated the degradation of cytosolic PrPs and restored cytosolic PrP-induced cytotoxicity. Moreover, we found that Hsp70 levels were up-regulated in cells expressing Cyto-PrP and in hamster brains infected with the scrapie agent 263K.

Conclusion

These data imply that Hsp70 has central role in the metabolism of cytosolic PrPs
Galanin-Expression and Galanin-Dependent Sensory Neurons Are Not Required for Itch
Authors: Holmes Fiona E , Vanderplank Penny , Wynick David
Published: December 2012

Background:

Galanin is a key modulator of nociception, and it is also required for the developmental survival of a subset of C-fibre sensory neurons which are critical to the mediation of neuropathic and inflammatory pain. However, the potential modulatory roles played by galanin, or the galanin-dependent neurons, in pruritoceptive mechanisms underlying the sensation of itch have not been investigated.

Findings:

Here we report that mice carrying a loss-of-function mutation in the galanin gene (Gal-KO) show no differences in spontaneous behavioural itch responses compared to wild-type (WT) controls. Similarly, the responses to a range of pruritogens are not significantly different between the two genotypes.

Conclusions:

These results suggest that neither galanin expression, nor the galanin-dependent subpopulation of sensory neurons is required for itch-related behaviours.
Interplay between neural-cadherin and vascular endothelial-cadherin in breast cancer progression
Authors: Rezaei Maryam , Friedrich Katrin , Wielockx Ben , Kuzmanov Aleksandar , Kettelhake Antje , Labelle Myriam , Schnittler Hans , Baretton Gustavo , Breier Georg
Published: December 2012

Introduction

Deregulation of cadherin expression, in particular the loss of epithelial (E)-cadherin and gain of neural (N)-cadherin, has been implicated in carcinoma progression. We previously showed that endothelial cell-specific vascular endothelial (VE)-cadherin can be expressed aberrantly on tumor cells both in human breast cancer and in experimental mouse mammary carcinoma. Functional analyses revealed that VE-cadherin promotes tumor cell proliferation and invasion by stimulating transforming growth factor (TGF)-β signaling. Here, we investigate the functional interplay between N-cadherin and VE-cadherin in breast cancer.

Methods

The expression of N-cadherin and VE-cadherin was evaluated by immunohistochemistry in a tissue microarray with 84 invasive human breast carcinomas. VE-cadherin and N-cadherin expression in mouse mammary carcinoma cells was manipulated by RNA interference or overexpression, and cells were then analyzed by immunofluorescence, reverse transcriptase-polymerase chain reaction, and western blot. Experimental tumors were generated by transplantation of the modified mouse mammary carcinoma cells into immunocompetent mice. Tumor growth was monitored, and tumor tissue was subjected to histological analysis.

Results

VE-cadherin and N-cadherin were largely co-expressed in invasive human breast cancers. Silencing of N-cadherin in mouse mammary carcinoma cells led to decreased VE-cadherin expression and induced changes indicative of mesenchymal-epithelial transition, as indicated by re-induction of E-cadherin, localization of β-catenin at the cell membrane, decreased expression of vimentin and SIP1, and gain of epithelial morphology. Suppression of N-cadherin expression also inhibited tumor growth in vivo, even when VE-cadherin expression was forced.

Conclusions

Our results highlight the critical role of N-cadherin in breast cancer progression and show that N-cadherin is involved in maintaining the malignant tumor cell phenotype. The presence of N-cadherin prevents the re-expression of E-cadherin and localization of β-catenin at the plasma membrane of mesenchymal mammary carcinoma cells. N-cadherin is also required to maintain the expression of VE-cadherin in malignant tumor cells but not vice versa. Thus, N-cadherin acts in concert with VE-cadherin to promote tumor growth.
Novel mechanism for mesenchymal stem cells in attenuating peritoneal adhesion: accumulating in the lung and secreting tumor necrosis factor α-stimulating gene-6
Authors: Wang Nan , Shao Yeqing , Mei Yan , Zhang Li , Li Qinggang , Li Diangeng , Shi Suozhu , Hong Quan , Lin Hongli , Chen Xiangmei
Published: December 2012

Introduction

We previously found that mesenchymal stem cells (MSCs) injected intravenously could attenuate peritoneal adhesion by secreting tumor necrosis alpha-stimulating gene (TSG)-6, while MSCs injected intraperitoneally could not. However, the underlying mechanism remains unclear. This study was designed to investigate the means by which MSCs exert their effects.

Methods

Rat bone marrow-derived MSCs/red fluorescent protein (RFP) were injected either intraperitoneally or intravenously into Sprague-Dawley (SD) rats at different time points after peritoneal scraping. Peritoneal adhesions were evaluated macroscopically at day 14 after scraping. The distribution of MSCs injected intraperitoneally or intravenously was traced by two-photon fluorescence confocal imaging and immunofluorescence microscopy. The co-localization of MSCs and macrophages in the lung and the spleen, and the expression of TSG-6 in MSCs trapped in the lung or the spleen were evaluated by immunofluorescence microscopy. The concentration of TSG-6 in serum was evaluated by ELISA. After intravenous injection of TSG-6- small interfering (si) RNA-MSCs, the expression of TSG-6 in MSCs and the concentration of TSG-6 in serum were reevaluated, and peritoneal adhesions were evaluated macroscopically and histologically.

Results

MSCs injected intraperitoneally failed to reduce peritoneal adhesion, and MSCs injected intravenously markedly improved peritoneal adhesion. Two-photon fluorescence confocal imaging showed that MSCs injected intravenously accumulated mainly in the lung, where they remained for seven days, and immunofluorescence microscopy showed few MSCs phagocytosed by macrophages. In contrast, large numbers of MSCs accumulated in the spleen with obvious phagocytosis by macrophages even at 4 hours after intraperitoneal injection. Immunofluorescence microscopy showed that MSCs that accumulated in the lung after intravenous injection could express TSG-6 within 12 hours, but TSG-6-siRNA-MSCs or MSCs accumulated in the spleen after intraperitoneal injection did not. ELISA showed that the concentration of TSG-6 in serum was increased at 4 hours after intravenous injection of MSCs, while there was no increase after injection of TSG-6-siRNA-MSCs or after intraperitoneal injection of MSCs. Moreover, intravenous injection of TSG-6-siRNA-MSCs failed to attenuate peritoneal adhesion.

Conclusions

Our findings suggest that intravenously injected MSCs accumulated in the lung and attenuated peritoneal adhesion by secreting TSG-6, but intraperitoneally injected MSCs were phagocytosed by macrophages in the spleen and failed to attenuate peritoneal adhesion.