bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: Study protocol of a single arm trial preparing an RCT [ISRCTN58562962]
Authors: Hinrichs Timo , Bucchi Claudio , Brach Michael , Wilm Stefan , Endres Heinz G , Burghaus Ina , Trampisch Hans-Joachim , Platen Petra
Published: August 2009

Background

Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted.

Methods

The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs.

Conclusion

A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme.

Trial registration

Current Controlled Trials ISRCTN58562962.
Systematic validation of predicted microRNAs for cyclin D1
Authors: Jiang Qiong , Feng Ming-Guang , Mo Yin-Yuan
Published: August 2009

Background

MicroRNAs are the endogenous small non-coding RNA molecules capable of silencing protein coding genes at the posttranscriptional level. Based on computer-aided predictions, a single microRNA could have over a hundred of targets. On the other hand, a single protein-coding gene could be targeted by many potential microRNAs. However, only a relatively small number of these predicted microRNA/mRNA interactions are experimentally validated, and no systematic validation has been carried out using a reporter system.

Methods

In this study, we used luciferease reporter assays to validate microRNAs that can silence cyclin D1 (CCND1) because CCND1 is a well known proto-oncogene implicated in a variety of types of cancers. We chose miRanda http://www.microRNA.org as a primary prediction method. We then cloned 51 of 58 predicted microRNA precursors into pCDH-CMV-MCS-EF1-copGFP and tested for their effect on the luciferase reporter carrying the 3'-untranslated region (UTR) of CCND1 gene.

Results

Real-time PCR revealed the 45 of 51 cloned microRNA precursors expressed a relatively high level of the exogenous microRNAs which were used in our validation experiments. By an arbitrary cutoff of 35% reduction, we identified 7 microRNAs that were able to suppress Luc-CCND1-UTR activity. Among them, 4 of them were previously validated targets and the rest 3 microRNAs were validated to be positive in this study. Of interest, we found that miR-503 not only suppressed the luciferase activity, but also suppressed the endogenous CCND1 both at protein and mRNA levels. Furthermore, we showed that miR-503 was able to reduce S phase cell populations and caused cell growth inhibition, suggesting that miR-503 may be a putative tumor suppressor.

Conclusion

This study provides a more comprehensive picture of microRNA/CCND1 interactions and it further demonstrates the importance of experimental target validation.
Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression
Authors: Tuhkanen Hanna , Soini Ylermi , Kosma Veli-Matti , Anttila Maarit , Sironen Reijo , Hämäläinen Kirsi , Kukkonen Laura , Virtanen Ismo , Mannermaa Arto
Published: August 2009

Background

Transcription factor Snail1 has a central role in induction of epithelial-mesenchymal transition (EMT). The aim of the present study was to elucidate the expression of Snail1 protein during epithelial ovarian tumourigenesis and to study the association of Snail1 expression with clinicopathological factors and prognosis.

Methods

Epithelial and stromal fibroblast-like fusiform cells of 14 normal ovarian samples, 21 benign, 24 borderline and 74 malignant epithelial ovarian tumours were studied for Snail1 protein using immunohistochemistry.

Results

Nuclei of surface peritoneal cells of normal ovaries (n = 14) were regarded as negative for Snail1. Nuclear expression of Snail1 protein in epithelial ovarian tumours was increased during tumour progression from precursor lesions into carcinomas both in epithelial (p = 0.006) and stromal cells (p = 0.007). Nuclei of benign tumours (n = 21) were negative for Snail1. In borderline tumours (n = 24) occasional positive epithelial cells were found in 2 (8%) samples and in 3 (13%) samples stromal cells were focally positive for Snail1. In carcinomas (n = 74) focal Snail1 staining in epithelial cells was present in 17 (23%) tumours, and in stromal cells in 18 (24%) tumours. Nuclear expression of Snail1 in epithelial or stromal cells was not associated with clinicopathological factors or prognosis.

Conclusion

Nuclear Snail1 expression seems to be related to tumour progression, and expression in borderline tumours indicates a role for Snail1 in early epithelial ovarian tumour development. Snail1 also appears to function more generally in tissue remodelling as positive staining was demonstrated in stromal cells.
The relationship between physical performance measures, bone mineral density, falls, and the risk of peripheral fracture: a cross-sectional analysis
Authors: Khazzani Hamza , Allali Fadoua , Bennani Loubna , Ichchou Linda , El Mansouri Laila , Abourazzak Fatima E , Abouqal Redouane , Hajjaj-Hassouni Najia
Published: August 2009

Background

Several factors, in addition to low bone mineral density (BMD), have been identified as risks for fractures, including reduced levels of physical activity, poor balance and low physical performance. The aim of this study was to evaluate the relationship between physical performance measures, BMD, falls, and the risk of peripheral fracture in a population sample of Moroccan women.

Methods

484 healthy women were included. Three measures were used to assess physical performance: timed get-up-and-go test 'TGUGT', five-times-sit-to-stand test '5 TSTS' and 8-feet timed walk '8 FTW'. The association between physical performance measures and BMD, peripheral fracture and falls was performed by univariate and multivariate analysis.

Results

The mean age was 55.1 years. Higher 'TGUGT', '5 TSTS', '8 FTW' test scores were associated with lower BMD measured at different sites (p range from < 0.001 to 0.005). The relationship between the three tests and BMD in all measured sites remained significant after multiple linear regression (p range from <0.001 to 0.026). In the group of post-menopausal patients, the scores of 'TGUGT' and '8 FTW' were significantly higher in fractured patients compared with patients without. After logistic regression, a score of 'TGUGT' > 14.2 sec, a score of '5 TSTS' > 12.9 sec and a score of '8 FTW' > 4.6 sec respectively, increased the probability of anterior peripheral fracture by 2.7, 2.2 and 2.3 (OR = 2.7; 95% CI = 1.2–6.4, OR = 2.2; 95% CI = 1.1–5.2; and OR = 2.3; 95% CI = 1.1–5.1). There was a significant positive correlation between the number of fall/year and the 3 tests. This correlation persisted after poisson regression.

Conclusion

This study suggested that low physical performance is associated with low BMD, and a high risk of history of falls and fractures.
Chronic pain in primary care. German figures from 1991 and 2006
Authors: Frießem Christine H , Willweber-Strumpf Anne , Zenz Michael W
Published: August 2009

Background

Until now only limited research has been done on the prevalence of chronic pain in primary care. The aim of this investigation was to study the health care utilisation of patients suffering from pain. How many patients visit an outpatient clinic because of the symptom of pain? These data were compared with data from a similar study in 1991, to investigate whether improvements had been achieved.

Methods

A total of 1201 consecutive patients visiting outpatient clinics were surveyed in six practices in the western part of Germany on randomly selected days by means of questionnaires. Topics were the point prevalence of pain and the period prevalence of chronic pain, its characteristics and its impact on daily life, as well as data on previous therapies for pain. A retrospective comparison was made with the data from a similar study with same design surveying 900 patients that took place in five practices during 1991.

Results

In 2006, pain was the main reason for consulting a doctor in 42.5% of all patients (1991: 50.3%). Of all respondents, 62% suffered from pain on the particular day of the consultation, and 40% reported that they had been suffering from pain for more than six months (1991: 36.4%). As many as 88.3% of patients with chronic pain reported a negative impact on their daily life due to this pain (1991: 68%), and 88.1% reported impairment of their working life because of chronic pain (1991: 59.1%).

Conclusion

Pain, and chronic pain in particular, is a central problem in primary care. Over the last 15 years, the number of patients suffering from chronic pain has not decreased. In nearly half of all cases, pain is still the reason for health care utilisation in outpatient clinics. Pain represents a major primary health care problem with enormous impact on public health. Improvements can only be achieved by improving the quality of health care at the primary care level.
Intraprostatic Botulinum Toxin Type A injection in patients with benign prostatic enlargement: duration of the effect of a single treatment
Authors: Silva João , Pinto Rui , Carvalho Tiago , Botelho Francisco , Silva Pedro , Oliveira Rui , Silva Carlos , Cruz Francisco , Dinis Paulo
Published: August 2009

Background

Botulinum Toxin Type-A (BoNT/A) intraprostatic injection can induce prostatic involution and improve LUTS and urinary flow in patients with Benign Prostatic Enlargement (BPE). However, the duration of these effects is unknown. The objective of this work was to determine the duration of prostate volume reduction after one single intraprostatic injection of 200U of Botulinum Toxin Type-A.

Methods

This is an extension of a 6 month study in which 21 frail elderly patients with refractory urinary retention and unfit for surgery were submitted to intraprostatic injection of BoNT/A-200U, by ultrasound guided transrectal approach. In spite of frail conditions, eleven patients could be followed during 18 months. Prostate volume, total serum PSA, maximal flow rate (Qmax), residual volume (PVR) and IPSS-QoL scores were determined at 1, 3, 6, 12 and 18 months post-treatment.

Results

Mean prostate volume at baseline, 82 ± 16 ml progressively decreased from month one coming to 49 ± 9,5 ml (p = 0,003) at month six. From this moment on, prostate volume slowly recovered, becoming identical to baseline at 18 months (73 ± 16 ml, p = 0.03). Albeit non significant, serum PSA showed a 25% decrease from baseline to month 6. The 11 patients resumed spontaneous voiding at month one. Mean Qmax was 11,3 ± 1,7 ml/sec and remained unchanged during the follow-up period. PVR ranged from 55 ± 17 to 82 ± 20 ml and IPSS score from10 to 12 points.

Conclusion

Intraprostatic BoNT/A injection is safe and can reduce prostate volume for a period of 18 months. During this time a marked symptomatic improvement can be maintained.
Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
Authors: Han Juying , Zhang Fuming , Xie Jin , Linhardt Robert J , Hiebert Linda M
Published: August 2009

Background

Heparan sulfate proteoglycans (HSPGs) contain glycosaminoglycan (GAG) chains made primarily of heparan sulfate (HS). Hyperglycemia in diabetes leads to endothelial injury and nephropathy, retinopathy and atherosclerosis. Decreased HSPG may contribute to diabetic endothelial injury. Decreased tissue HS in diabetes has been reported, however, endothelial HS changes are poorly studied.

Objective

To determine total GAGs, including HS, in endothelium under hyperglycemic conditions and the protective effect of insulin and heparin.

Methods

Confluent primary porcine aortic endothelial cells (PAECs) were divided into control, glucose (30 mM), insulin (0.01 unit/ml) and glucose plus insulin treatment groups for 24, 48 and 72 hours. Additionally, PAECs were treated with glucose, heparin (0.5 μ g/ml) and glucose plus heparin for 72 hours. GAGs were isolated from cells and medium. GAG concentrations were determined by the carbazole assay and agarose gel electrophoresis.

Results

GAGs were significantly increased only in control and glucose plus insulin groups at 72 versus 24 hours. Glucose decreased cell GAGs and increased medium GAGs, and insulin alone decreased cell GAGs at all times compared to control. In the glucose plus insulin group, cell GAGs were less than control at 24 hours, and greater than glucose or insulin alone at 48 and 72 hours while GAGs in medium were greater than control at all times and glucose at 72 hours. Heparin increased GAGs in glucose treated cells and medium.

Conclusion

High glucose and insulin alone reduces endothelial GAGs. In hyperglycemic conditions, heparin or insulin preserves GAGs which may protect cells from injury. Insulin is an effective diabetic therapy since it not only lowers blood glucose, but also protects endothelium.
Respiratory and skin health among glass microfiber production workers: a cross-sectional study
Authors: Sripaiboonkij Penpatra , Sripaiboonkij Nintita , Phanprasit Wantanee , Jaakkola Maritta S
Published: August 2009

Background

Only a few studies have investigated non-malignant respiratory effects of glass microfibers and these have provided inconsistent results. Our objective was to assess the effects of exposure to glass microfibers on respiratory and skin symptoms, asthma and lung function.

Methods

A cross-sectional study of 102 workers from a microfiber factory (response rate 100%) and 76 office workers (73%) from four factories in Thailand was conducted. They answered a questionnaire on respiratory health, occupational exposures, and lifestyle factors, and performed spirometry. Measurements of respirable dust were available from 2004 and 2005.

Results

Workers exposed to glass microfibers experienced increased risk of cough (adjusted OR 2.04), wheezing (adjOR 2.20), breathlessness (adjOR 4.46), nasal (adjOR 2.13) and skin symptoms (adjOR 3.89) and ever asthma (adjOR 3.51), the risks of breathlessness (95%CI 1.68–11.86) and skin symptoms (1.70–8.90) remaining statistically significant after adjustment for confounders. There was an exposure-response relation between the risk of breathlessness and skin symptoms and increasing level of microfiber exposure. Workers exposed to sensitizing chemicals, including phenol-formaldehyde resin, experienced increased risk of cough (3.43, 1.20–9.87) and nasal symptoms (3.07, 1.05–9.00).

Conclusion

This study provides evidence that exposure to glass microfibers increases the risk of respiratory and skin symptoms, and has an exposure-response relation with breathlessness and skin symptoms. Exposure to sensitizing chemicals increased the risk of cough and nasal symptoms. The results suggest that occupational exposure to glass microfibers is related to non-malignant adverse health effects, and that implementing exposure control measures in these industries could protect the health of employees.
JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma
Authors: Chang Qingshan , Chen Jianguo , Beezhold Kevin J , Castranova Vince , Shi Xianglin , Chen Fei
Published: August 2009

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established.

Results

In the present study, we reported HCC signature genes based on the JNK1 activation status in 31 HCC specimens relative to the matched distal noncancerous liver tissue from 31 patients. The HCCs with high JNK1 (H-JNK1) and low JNK1 (L-JNK1) were sub-grouped. Two different signature gene sets for both H-JNK1 and L-JNK1 HCC were identified through gene expression profiling. A striking overlap of signature genes was observed between the H-JNK1 HCC and the hepatoblastoma or hepatoblastoma-type HCC. Many established biomarkers for hepatic progenitor cells were over-expressed in H-JNK1 HCC, including AFP, TACSTD1, KRT19, KRT7, THY1, and PROM1. In addition, the majority of the most up-regulated genes were those associated with metastasis and earlier recurrence, whereas the genes for normal liver function were substantially down-regulated in H-JNK1 HCC tissue. A Kaplan-Meier plot demonstrated that the survival of the patients with H-JNK1 HCC was severely impaired.

Conclusion

Accordingly, we believe that the H-JNK1 HCC may originate from hepatic progenitor cells and is associated with poorer prognosis. The status of JNK1 activation in HCC tissue, thus, might be a new biomarker for HCC prognosis and therapeutic targeting.
Cardiac magnetic resonance versus transthoracic echocardiography for the assessment of cardiac volumes and regional function after myocardial infarction: an intrasubject comparison using simultaneous intrasubject recordings
Authors: Gardner Blake I , Bingham Scott E , Allen Marvin R , Blatter Duane D , Anderson Jeffrey L
Published: August 2009

Background

Although echocardiography is commonly used to evaluate cardiac function after MI, CMR may provide more accurate functional assessment but has not been adequately compared with echo. The primary study objective was to compare metrics of left ventricular volumes and global and regional function determined by cardiac magnetic resonance (CMR) and echocardiography (echo) in patients (pts) with recent myocardial infarction (MI).

Methods

To compare CMR with echo, 47 consecutive patients (pts 70% male; mean age = 66 ± 11 years) with MI >6 wks previously and scheduled for imaging evaluation were studied by both echo and CMR within 60 min of each other. Readers were blinded to pt information. Pearson's correlation coefficient, paired t-tests, and chi-square tests were used to compare CMR and echo measures. Further comparisons were made between pts and 30 normal controls for CMR and between pts and published normal ranges for echo.

Results

Measures of volume and function correlated moderately well between CMR and echo (r = 0.54 to 0.75, all p < 0.001), but large and systematic differences were noted in absolute measurements. Echo underestimated left ventricular (LV) volumes (by 69 ml for end-diastolic, 35 ml for end-systolic volume, both p < 0.001), stroke volume (by 34 ml, p < 0.001), and LV ejection fraction (LVEF) (by 4 percentage point, p = 0.02). CMR was much more sensitive to detection of segmental wall motion abnormalities (p < 0.001). CMR comparisons with normal controls confirmed an increase in LV volumes, a decrease in LVEF, and preservation of stroke volume after MI.

Conclusion

This intra subject comparison after MI found large, systematic differences between CMR and echo measures of volumes, LVEF, and wall motion abnormality despite moderate inter-modality correlations, with echo underestimating each metric. CMR also provided superior detection and quantification of segmental function after MI. Serial studies of LV function in individual patients should use the same modality.
The Drosophila immunoglobulin gene turtle encodes guidance molecules involved in axon pathfinding
Authors: Al-Anzi Bader , Wyman Robert J
Published: August 2009

Background

Neuronal growth cones follow specific pathways over long distances in order to reach their appropriate targets. Research over the past 15 years has yielded a large body of information concerning the molecules that regulate this process. Some of these molecules, such as the evolutionarily conserved netrin and slit proteins, are expressed in the embryonic midline, an area of extreme importance for early axon pathfinding decisions. A general model has emerged in which netrin attracts commissural axons towards the midline while slit forces them out. However, a large number of commissural axons successfully cross the midline even in the complete absence of netrin signaling, indicating the presence of a yet unidentified midline attractant.

Results

The evolutionarily conserved Ig proteins encoded by the turtle/Dasm1 genes are found in Drosophila, Caenorhabditis elegans, and mammals. In Drosophila the turtle gene encodes five proteins, two of which are diffusible, that are expressed in many areas, including the vicinity of the midline. Using both molecular null alleles and transgenic expression of the different isoforms, we show that the turtle encoded proteins function as non-cell autonomous axonal attractants that promote midline crossing via a netrin-independent mechanism. turtle mutants also have either stalled or missing axon projections, while overexpression of the different turtle isoforms produces invasive neurons and branching axons that do not respect the histological divisions of the nervous system.

Conclusion

Our findings indicate that the turtle proteins function as axon guidance cues that promote midline attraction, axon branching, and axonal invasiveness. The latter two capabilities are required by migrating axons to explore densely packed targets.
The influence of human papillomavirus type and HIV status on the lymphomononuclear cell profile in patients with cervical intraepithelial lesions of different severity
Authors: Gonçalves Maria Alice G , Soares Edson G , Donadi Eduardo A
Published: August 2009

Background

Immunological alterations are implicated in the increased prevalence of high-grade squamous intraepithelial lesions (HG-SIL) and persistent human papillomavirus (HPV) infection. This study evaluated the expression of CD4, CD8, CD25 (IL-2Rα) and CD28 antigens from SIL biopsies, stratified by HIV status and HPV-type. Biopsies specimens from 82 (35 HIV+) women with a normal cervix, low-grade (LG-SIL) or high-grade lesions (HG-SIL) were studied. CD molecule expression was evaluated by immunohistochemistry and HPV detection/typing performed using PCR techniques.

Results

CD4 stromal staining was increased in patients with HPV18. Women with HPV16 infection showed decreased: a) CD8 and CD25 stromal staining, b) CD25 staining in LG-SIL epithelium and in HG-SIL stroma. In HIV-women samples, CD28 epithelial staining and CD8 stromal staining surrounding metaplastic epithelium were less intense and even absent, as compared to HIV+women. Both epithelial and stromal CD8 staining was more intense in the HG-SIL/HIV+group than in the HG-SIL/HIV-group. Positive correlations were observed between CD4/CD25, CD4/CD28 and CD25/CD28 in the stroma and CD25/CD28 in the epithelium.

Conclusion

HIV status and HPV-type may influence the lymphomononuclear cell profile present in the spectrum of cervical lesions. The knowledge of the infiltrating cell profile in cervical tumours may help the development of specific anti-tumoural strategies.
Effector mechanisms of interleukin-17 in collagen-induced arthritis in the absence of interferon-γ and counteraction by interferon-γ
Authors: Kelchtermans Hilde , Schurgers Evelien , Geboes Lies , Mitera Tania , Van Damme Jo , Van Snick Jacques , Uyttenhove Catherine , Matthys Patrick
Published: August 2009

Introduction

Interleukin (IL)-17 is a pro-inflammatory cytokine in rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Since interferon (IFN)-γ inhibits Th17 cell development, IFN-γ receptor knockout (IFN-γR KO) mice develop CIA more readily. We took advantage of this model to analyse the mechanisms of action of IL-17 in arthritis. The role of IFN-γ on the effector mechanisms of IL-17 in an in vitro system was also investigated.

Methods

IFN-γR KO mice induced for CIA were treated with anti-IL-17 or control antibody. The collagen type II (CII)-specific humoral and cellular autoimmune responses, myelopoiesis, osteoclastogenesis, and systemic cytokine production were determined. Mouse embryo fibroblasts (MEF) were stimulated with IL-17, tumor necrosis factor (TNF)-α and the expression of cytokines and chemokines were determined.

Results

A preventive anti-IL-17 antibody treatment inhibited CIA in IFNγR KO mice. In the joints of anti-IL-17-treated mice, neutrophil influx and bone destruction were absent. Treatment reduced the cellular autoimmune response as well as the splenic expansion of CD11b+ cells, and production of myelopoietic cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-6. IL-17 and TNF-α synergistically induced granulocyte chemotactic protein-2 (GCP-2), IL-6 and receptor activator of NFκB ligand (RANKL) in MEF. This induction was profoundly inhibited by IFN-γ in a STAT-1 (signal transducer and activator of transcription-1)-dependent way.

Conclusions

In the absence of IFN-γ, IL-17 mediates its pro-inflammatory effects mainly through stimulatory effects on granulopoiesis, neutrophil infiltration and bone destruction. In vitro IFN-γ profoundly inhibits the effector function of IL-17. Thus, aside from the well-known inhibition of the development of Th17 cells by IFN-γ, this may be an additional mechanism through which IFN-γ attenuates autoimmune diseases.
Development and validation of the self-administered Fibromyalgia Assessment Status: a disease-specific composite measure for evaluating treatment effect
Authors: Salaffi Fausto , Sarzi-Puttini Piercarlo , Girolimetti Rita , Gasparini Stefania , Atzeni Fabiola , Grassi Walter
Published: August 2009

Introduction

The Fibromyalgia Impact Questionnaire (FIQ) is a composite disease-specific measure validated for fibromyalgia (FM), but it is rarely used in clinical practice. The objective was to develop and analyse the psychometric properties of a new composite disease-specific index (Fibromyalgia Assessment Status, FAS), a simple self-administered index that combines a patient's assessment of fatigue, sleep disturbances and pain evaluated on the basis of the 16 non-articular sites listed on the Self-Assessment Pain Scale (SAPS) in a single measure (range 0 to 10).

Methods

The FAS index was constructed using a traditional development strategy, and its psychometric properties were tested in 226 FM patients (209 women, 17 men); whose disease-related characteristics were assessed by means of an 11-numbered circular numerical rating scale (NRS) for pain, fatigue, sleep disturbances and general health (GH), the tender point score (TPS), the SAPS, the FIQ, and the SF-36. A group of 226 rheumatoid arthritis (RA) patients was used for comparative purposes. Of the 179 FM patients who entered the follow-up study, 152 completed the three-month period and were included in the responsiveness analyses. One hundred and fifty-four patients repeated the FAS questionnaire after an interval of one week, and its test/re-test reliability was calculated. Responsiveness was evaluated on the basis of effect size and the standardised response mean.

Results

The FAS index fulfilled the established criteria for validity, reliability and responsiveness. Factor analysis showed that SAPS and fatigue contributed most, and respectively explained 47.4% and 31.2% of the variance; sleep explained 21.3%. Testing for internal consistency showed that Cronbach's alpha was 0.781, thus indicating a high level of reliability. As expected, closer significant correlations were found when FAS was compared with total FIQ (rho = 0.347; P < 0.0001) and the FIQ subscales, particularly job ability, tiredness, fatigue and pain (all P < 0.0001), but the correlation between FAS and the mental component summary scale score (MCS) of the SF-36 (rho = -0.531; P < 0.0001) was particularly interesting. Test/re-test reliability was satisfactory. The FAS showed the greatest effect size. The magnitude of the responsiveness measures was statistically different between FAS (0.889) and the FIQ (0.781) (P = 0.038), and between the SF-36 MCS (0.434) and the SF-36 physical component summary scale score (PCS) (0.321) (P < 0.01).

Conclusions

The self-administered FAS is a reliable, valid and responsive disease-specific composite measure for assessing treatment effect in patients with FM.
CCR1-mediated activation of nuclear factor-κB in THP-1 monocytic cells involvespertussistoxin-insensitive Gα14 and Gα16 signaling cascades
Authors: Lee Maggie M K , Wong Yung H
Published: August 2009

Multiple signaling intermediates are involved in the regulation of nuclear factor-kB by chemokines in monocytic cells.

Agonists of CC chemokine receptor CCR1 contribute to the pathogenesis of autoimmune and other inflammatory diseases, possibly via the regulation of the transcription factor NF-κB. CCR1 and CCR2b have been demonstrated to use PTX-insensitive Gα14 and Gα16 to stimulate PLCβ in cotransfected cells, and Gα14 and Gα16 are capable of activating NF-κB. The coexpression of Gα14, Gα16, and CCR1 in human monocytic THP-1 cells suggests that CCR1 may use Gα14 or Gα16 to induce NF-κB activation. Here, we demonstrated that a CCR1 agonist, Lkn-1, stimulated NF-κB phosphorylation via PTX-insensitive G proteins in THP-1 cells. Lkn-1 also mediated IKK/NF-κB phosphorylations in HEK293 cells overexpressing CCR1 and Gα14/16. Using various kinase inhibitors, Raf-1, MEK1/2, PLCβ, PKC, CaM, CaMKII, and c-Src were found to participate in Lkn-1-stimulated IKK/NF-κB phosphorylations in THP-1 and transfected HEK293 cells. Although c-Jun N-terminal kinase and p38 MAPK were activated by Lkn-1, they were not required in Lkn-1-induced IKK phosphorylation. The ability of CCR1 to signal through Gα14/16 thus provides a linkage for chemokines to regulate NF-κB-dependent responses.
Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice
Authors: Anastassiadis Konstantinos , Fu Jun , Patsch Christoph , Hu Shengbiao , Weidlich Stefanie , Duerschke Kristin , Buchholz Frank , Edenhofer Frank , Stewart A. Francis
Published: August 2009

Tyrosine site-specific recombinases (SSRs) including Cre and FLP are essential tools for DNA and genome engineering. Cre has long been recognized as the best SSR for genome engineering, particularly in mice. Obtaining another SSR that is as good as Cre will be a valuable addition to the genomic toolbox. To this end, we have developed and validated reagents for the Dre-rox system. These include an Escherichia coli-inducible expression vector based on the temperature-sensitive pSC101 plasmid, a mammalian expression vector based on the CAGGs promoter, a rox-lacZ reporter embryonic stem (ES) cell line based on targeting at the Rosa26 locus, the accompanying Rosa26-rox reporter mouse line, and a CAGGs-Dre deleter mouse line. We also show that a Dre-progesterone receptor shows good ligand-responsive induction properties. Furthermore, we show that there is no crossover recombination between Cre-rox or Dre-loxP. Hence, we add another set of efficient tools to the genomic toolbox, which will enable the development of more sophisticated mouse models for the analysis of gene function and disease.
Temperature dependence of the luminescent photoelastic coating technique
Authors: Esirgemez E , Hubner J P
Published: August 2009

This paper presents the optical strain response results of a luminescent photoelastic coating (LPC) at elevated temperatures up to 100 °C. The LPC technique is used to acquire full-field stress and strain measurements on structural components. Differing from traditional reflective photoelastic coatings, an LPC uses a luminescent dye that partially retains the induced polarization changes in the illumination field through the coating and provides a relatively high signal response at oblique incidence angles. These characteristics enable the LPC technique to measure the full-field separated principal strains and their directions using oblique excitation. The strain-dependent response of the coating is affected by several parameters such as the luminescent polarization efficiency, optical sensitivity, coating absorptivity, and effective excitation or emission wavelength. The effect of temperature elevation on these parameters is important to characterize if the technique is extended to high-temperature or cyclic-temperature environments. Temperature sensitivity is documented and measurement uncertainty is addressed. Overall, the measured optical strain response decreased by 77 per cent between 24 °C and 92 °C with a steepest decent of –8 per cent/°C at 65 °C.
Generalized spatial-gradient-based digital image correlation for displacement and shape measurement with subpixel accuracy
Authors: Pan B , Wang Z , Xie H
Published: August 2009

A generalized spatial-gradient-based digital image correlation (DIC) method is proposed for subpixel-accuracy displacement and shape measurement. The proposed method overcomes the limitations in existing spatial-gradient-based DIC methods by adopting a generalized linear intensity-change model, which can cope well with linear variation in lighting illumination and greyscale intensity change of an object's surface during the measurement. In addition, various displacement mapping functions can be easily incorporated into the proposed intensity-change model to approximate the underlying deformation of the subset, and a simple iterative least-squares algorithm is employed to detect the desired displacement parameters with a robust noise-proof performance. To evaluate the performance of the proposed technique, both computer simulation and an actual experiment have been carried out. The results clearly demonstrate that the proposed method can accurately measure the shape and displacement field, even when substantial intensity variations exist in the experimental images.
Parametric study on near-dry wire electrodischarge machining of polycrystalline diamond-coated tungsten carbide material
Authors: Jia Y , Kim B S , Hu D J , Ni J
Published: August 2009

Polycrystalline diamond (PCD)-coated tungsten carbide (WC) is a high-performance cutting tool material widely used in industry for cutting or ultra-precision cutting of advanced engineering materials, but it is difficult to machine using conventional machining techniques owing to its high hardness. However, wire electrical discharge machining (wire EDM) offers advantages in machining PCD-coated WC in terms of process reliability and flexibility to machine different shapes. To relieve pollution issues associated with traditional wet wire EDM, the present study investigated the feasibility of near-dry wire EDM of PCD-coated WC cutting tool material using deionized water and air mist. A parametric study on spark cycle and spark duration was carried out, and the effect of these two important wire EDM process parameters on machining performance in terms of material removal rate (MRR) and surface roughness ( Ra) was analysed. Compared with conventional wet wire EDM, near-dry wire EDM consistently produces better Ra values on the PCD-coated WC workpiece, but near-dry wire EDM produces lower MRR than wet wire EDM under some conditions.
The flow around a pipeline with a spoiler
Authors: Oner A A
Published: August 2009

Offshore pipelines are buried in the seabed to be protected from the damage caused by hydrodynamic forces or by human activities. However, because of soil erosion and interaction of currents with the pipeline on the moveable seabed, the processes of local scouring and, sometimes, self-burial of pipelines take place. To increase the rate and extent of scouring, the technique of attaching a spoiler to the pipeline has been developed. In this study, two-dimensional, steady, turbulent flow around a horizontal pipeline with a spoiler near a smooth wall is investigated experimentally by using the particle image velocimetry technique. The effect of the spoiler was examined for the Reynolds numbers of ReD=840, 1500, 4150, and 9500 based on the pipe diameter. The effect of the spoiler on the process of scouring is investigated through the parameters of the measured instantaneous and time-averaged patterns of the velocity vector field and the streamline topology. The results indicated that the attachment of the spoiler to the pipeline increases the length of the upstream and downstream separation regions and it is also observed that the spoiler does not significantly increase the rate of the flow that passes through the gap and the shear stress acting on the seabed.
A three-dimensional model of the boat—oars—rower system using ADAMS and LifeMOD commercial software
Authors: Serveto S , Barré S , Kobus J-M , Mariot J-P
Published: August 2009

This paper presents a numerical model of the boat—oars—rower system in a three-dimensional multibody dynamics approach using the ADAMS commercial software. The system is composed of four main parts: a skiff, two oars and a rower. The boat and oar mechanical model takes into account all boat settings and kinematic constraints, thus permitting a sophisticated model personalization. The rower skeletal model is built in LifeMOD (an ADAMS plug-in) software. In the example, a skilled rower is modelled with 19 human segments and 18 human joints which are personalized to the rower using the 32 external anthropometric data of the GEBOD program. In order to focus the tests on the rower on boat model, simulations are performed with basic hydrodynamic models for a single degree of freedom for the boat at first and then three degrees of freedom are used to show the potential of the model. The model is driven with five command signals, three oar rotations, seat movement, and lower torso rotation. The computed boat velocity is in good agreement with on-water measurements and a sensitivity test consisting of small variations of rowing technique allows the authors to be confident of the ability of the model regarding future optimization studies.
Comparison between common models of forces on oar blades and forces measured by towing tank tests
Authors: Barré S , Kobus J-M
Published: August 2009

This paper describes the hydrodynamic forces on oar blades and compares measured data with common models: one model using a normal force coefficient and the other using drag and lift coefficients. The data were obtained from tests in towing tanks on blades at reduced scale (typically 0.7). The measurement device can reproduce oar movements and measure the six components of the hydrodynamic efforts. These tests provide a better control, precision, and repeatability than measurements on water. The experimental modelling leads to defining the oar strokes using only the maximum rotation rate and an advance number, which can also be defined as basic efficiency. These movements are simplified but remain representative of the main characteristics of the unsteady working of oars. The measurements show how the direction and zero-torque point influence instantaneous efficiency. They also show that the force evolution can be described using the maximum values of drag and lift coefficients. These depend on the unsteadiness, characterized by a parameter equal to the difference between the velocities of the two blade edges divided by the normal component of the velocity of the blade centre. This parameter, fully related to the advance number, can be considered as a reduced frequency.
The Economics of Two-Sided Markets
Authors: Rysman Marc
Published: August 2009

Broadly speaking, a two-sided market is one in which 1) two sets of agents interact through an intermediary or platform, and 2) the decisions of each set of agents affects the outcomes of the other set of agents, typically through an externality. In the case of a video game system, the intermediary is the console producer—Sony in the scenario above—while the two sets of agents are consumers and video game developers. Neither consumers nor game developers will be interested in the PlayStation if the other party is not. Similarly, a successful payment card requires both consumer usage and merchant acceptance, where both consumers and merchants value each others' participation. Many more products fit into this paradigm, such as search engines, newspapers, and almost any advertiser-supported media (examples in which consumers typically negatively value, rather than positively value, the participation of the other side), as well as most software or title-based operating systems and consumer electronics. This paper seeks to explain what two-sided markets are and why they interest economists. I discuss the strategies that firms typically consider, and I highlight a number of puzzling outcomes from the perspective of the economics of two-sided markets. Finally, I consider the implications for public policy, particularly antitrust and regulatory policy, where there have been a number of recent issues involving media, computer operating systems, and payment cards.
The Economics of Online Crime
Authors: Moore Tyler , Clayton Richard , Anderson Ross
Published: August 2009

This paper will focus on online crime, which has taken off as a serious industry since about 2004. Until then, much of the online nuisance came from amateur hackers who defaced websites and wrote malicious software in pursuit of bragging rights. But now criminal networks have emerged—online black markets in which the bad guys trade with each other, with criminals taking on specialized roles. Just as in Adam Smith's pin factory, specialization has led to impressive productivity gains, even though the subject is now bank card PINs rather than metal ones. Someone who can collect bank card and PIN data, electronic banking passwords, and the information needed to apply for credit in someone else's name can sell these data online to anonymous brokers. The brokers in turn sell the credentials to specialist cashiers who steal and then launder the money. We will examine the data on online crime; discuss the collective-action aspects of the problem; demonstrate how agile attackers shift across national borders as earlier targets wise up to their tactics; describe ways to improve law-enforcement coordination; and we explore how defenders' incentives affect the outcomes.
The Online Advertising Industry: Economics, Evolution, and Privacy
Authors: Evans David S
Published: August 2009

Online advertising accounts for almost 9 percent of all advertising in the United States. This share is expected to increase as more media is consumed over the Internet and as more advertisers shift spending to online technologies. The expansion of Internet-based advertising is transforming the advertising business by providing more efficient methods of matching advertisers and consumers and transforming the media business by providing a source of revenue for online media firms that competes with traditional media firms. The precipitous decline of the newspaper industry is one manifestation of the symbiotic relationship between online content and advertising. Online-advertising is provided by a series of interlocking multisided platforms that facilitate the matching of advertisers and consumers. These intermediaries increasingly make use of detailed individual data, predictive methods, and matching algorithms to create more efficient matches between consumers and advertisers. Some of their methods raise public policy issues that require balancing benefits from providing consumers more valuable advertising against the possible loss of valuable privacy.
What Are Grades Made Of?
Authors: Achen Alexandra C , Courant Paul N
Published: August 2009

The term “grade inflation” covers a multitude of phenomena, some of which are even alleged to be sins. Continuing increases in average grades have been widely documented in many universities over the last several decades. Also widely documented, and often associated with grade inflation, are systematic differences in grade levels by field of study, with a common belief that the sciences and math grade harder than the social sciences, which in turn grade harder than the humanities—and that economics behaves more like the natural sciences than like the social sciences. The general persistence of these relative differences in grades seem to us to be more interesting and more difficult to explain than the persistence of modest grade inflation in general, and they are the principal focus of this paper. Why, for example, should average grades in English be much higher than average grades in chemistry? And what is going on when relative grades change, when a department's grading practices change markedly relative to other departments? We explore such questions using detailed data on grades at the University of Michigan from Fall 1992 through Winter 2008.
Grade Information and Grade Inflation: The Cornell Experiment
Authors: Bar Talia , Kadiyali Vrinda , Zussman Asaf
Published: August 2009

Grade inflation and high grade levels have been subjects of concern and public debate in recent decades. In the mid-1990s, Cornell University's Faculty Senate had a number of discussions about grade inflation and what might be done about it. In April 1996, the Faculty Senate voted to adopt a new grade reporting policy which had two parts: 1) the publication of course median grades on the Internet; and 2) the reporting of course median grades in students' transcripts. The policy change followed the determination of a university committee that “it is desirable for Cornell University to provide more information to the reader of a transcript and produce more meaningful letter grades.” It was hoped that “More accurate recognition of performance may encourage students to take courses in which the median grade is relatively low.” The median grade policy has remained to date only partially implemented: median grades have been reported online since 1998 but do not yet appear in transcripts. We evaluate the effect of the implemented policy on patterns of course choice and grade inflation. Specifically, we test two related hypotheses: First, all else being equal, the availability of online grade information will lead to increased enrollment into leniently graded courses. Second, high-ability students will be less attracted to the leniently graded courses than their peers. Building on these results we perform an exercise that identifies the extent to which the change in student behavior resulted in an increase in the university-wide mean grade.