bluuebunny/crossref_metadata_2025 huggingface dataset:
Finish milling system for extra-large rotors
Authors: Holmes C S , Shutt G , Matturi S
Published: May 2011

Holroyd Precision has produced the largest machine to date for the roughing and finishing of outsize rotors for the gas processing industry. Weighing over 8 tonne, these stainless steel rotors required a special machine tool able to cater for diameters up to 850 mm. The paper reviews the design and manufacture of the machine, including tooling, and describes some novel machine features.
Design of a novel, one-sided, pedal-activated wheelchair
Authors: Lin T-Y , Hsiao K-H , Yao H-W
Published: May 2011

The present paper proposes the design of a novel, one-sided, pedal-activated wheelchair for patients with hemiplegia or hemiparesis. The design comprises a planetary hub transmission, which is embedded in the hub of the wheelchair, with drive, neutral, and reverse modes. The paper first discusses the structural characteristics and motion transmission of the wheelchair, and then presents the motion design of the hub transmission, followed by assembly and testing of the prototype. The results confirm that the proposed wheelchair and hub transmission can meet users’ demands, thus improving comfort and independence.
Employee Impressions of a Manager
Authors: Francis Clare A.
Published: May 2011

This study examines computerized simulations of employee impressions of a manager in specific manager-employee interactions. Prior research has shown that employee impressions play a significant role in work outcomes including job performance, job performance appraisals, acceptance of change, and relationship quality to mention a few. This project examines the validity of affect control theory through application of software INTERACT, the tool that operationalizes theory principles to predict impressions and other social interaction outcomes. The key ingredients to the theory are fundamental sentiments, quantified in EPA (evaluation, potency, activity) profile dimensions on semantic differential scales ranging from −4.3 to +4.3. The theory holds that people intuitively rely on sentiments that prevail among a cultural group and extend across time. It is proposed that these sentiments maintain meaning and order in the lives of employees at work and for people in general in social life. The research compares computer-simulated predictions with experimental results for comparable manager-employee interactions. The hypothesis is supported with highly significant results.
Discontinuity effects in dynamically loaded tilting pad journal bearings
Authors: Thomsen K , Klit P , Vølund A
Published: May 2011

This article describes two discontinuity effects that can occur when modelling radial tilting pad bearings subjected to high dynamic loads. The first effect to be treated is a pressure build-up discontinuity effect. The second effect is a contact-related discontinuity that disappears when a contact force is included in the theoretical model. Methods for avoiding the pressure build-up discontinuity effect are proposed.
Perceptions of political party corruption and voting behaviour in Poland
Authors: Slomczynski Kazimierz , Shabad Goldie
Published: May 2011

Do perceptions of political party corruption play a significant role in vote choice? More specifically, is intention to vote for a specific party influenced by perceptions of corruption of that party, as well as by perceptions of the degree of corruption of competing parties? To determine whether perceptions of political party corruption matter at all for voters' preferences, we propose a party choice model in which we estimate the influence of perceptions of corruption of each party, net of other variables, on vote intention. We focus on Poland, and use data from the Polish Panel survey, POLPAN, 1988–2008. Our analyses indicate that perceptions of political party corruption have an effect on the decision to participate in elections, on intention to vote for a particular party and on vote choice regardless of which party is chosen. Assessments of party malfeasance matter even when other determinants of the vote are considered.
Collective remembering through the materiality and organization of war memorials
Authors: Beckstead Zachary , Twose Gabriel , Levesque-Gottlieb Emily , Rizzo Julia
Published: May 2011

This article investigates how material objects fit into societal discourses of remembering; the authors focus on how the spatial and material composition of objects can affect subjects, thus suggesting particular meanings and engagements. In particular, they investigate war memorials as cultural objects and products of social discourses, but emphasize that the memorials are not reducible to these discourses. Rather, the materials used in the creation of war memorials as well as their holistic organization constitute vital aspects of the memorial site and its ability to engage individuals and groups in socially desirable and personally meaningful processes. The authors analyze the Massachusetts Vietnam Veterans Memorial, taking into account the holistic material organization, hyper-generalization of signs, symbolic functions, and social suggestions that the memorial provides for visitors passing through. They argue that, partially through its very materiality, the memorial guides the direction of viewers’ affective response, leading to particular interpretations and reactions.
Cognition, materiality and monsters: the cultural transmission of counter-intuitive forms in Bronze Age societies
Authors: Wengrow David
Published: May 2011

In seeking to explain why some cultural traits are more ‘catching’ than others, evolutionary anthropologists have invoked the influence of cognitive constraints on the transmission of culture. Pascal Boyer’s explanation of the global popularity of religious beliefs in terms of their psychologically ‘counter-intuitive’ nature is a strong example. Drawing upon archaeological evidence from early civilizations, this article argues that such an approach does not in fact account satisfactorily for the observable distribution of a central type of counter-intuitive representation: that of the composite figure, or ‘monster’. A surprising feature of that distribution is the scarcity of composite figures in prehistoric art, prior to the Urban Revolution of the 4th millennium BC, after which their spread follows a highly patterned and selective (rather than ‘contagious’) trajectory of expansion. In interpreting this patterned spread of counter-intuitive forms, technological and institutional factors are brought into account alongside cognitive ones, with wider methodological implications for evolutionary approaches to the transmission of culture.
Porkin’ Pig goes to Magaluf
Authors: Andrews Hazel
Published: May 2011

This article discusses the symbolic role of pigs in the Mediterranean charter-tourist resort of Magaluf, Mallorca, based on periods of participant observation. The significance of pigs has been explored in relation to other cultures, notably Papua New Guinea, but work on the animal’s importance in British culture is less well documented. Taking Baudrillard’s concept of a system of objects, this article links the pig to other objects of material culture and demonstrates how the pig represents aspects of touristic identity and practice and can also be seen to speak for elements of British identity.
What Might a Person-Centred Model of Teacher Education Look Like in the 21st Century? The Transformism Model of Teacher Education
Authors: Dyson Michael
Published: May 2011

This article focuses on Big Picture thinking about 21st-century teacher education and presents a conceptual shift as the result of two decades of research and practice centred around an understanding that we live in a world troubled by a massive breakdown in relationships. Through reflection within four specific educational contexts and with the recognition of a need for the personal and social development of teachers, a person-centred model of teacher education, the transformism model, has been developed. The transformism, or evolution of teacher education, seeks to use a different mind-set, or a changed psychology, which moves away from a focus on the control of others by those who think they know what is best. Rather it is about transformative learning, achieved through reflection within a landscape of transformation. Effective teacher education, using this model embraces Gardner’s Five Minds for the Future and the embedding of Glasser’s choice theory. The conceptual shift occurs through a major change in consciousness and the concomitant development of a worldview rather than a me view.
Hebbian-Type Stimulation During Robot-Assisted Training in Patients With Stroke
Authors: Buetefisch Cathrin , Heger Roman , Schicks Wilfried , Seitz Rudiger , Netz Johannes
Published: May 2011

Background. Training-related improvements in motor function are associated with changes in movement representation of the primary motor cortex (M1). In healthy individuals, transcranial magnetic stimulation (TMS) of M1 delivered in a strict temporal relationship (Hebbian-type stimulation) during execution of movements enhances these effects and is superior to random stimulation. Objective. The authors tested whether training combined with Hebbian-type M1 stimulation enhances M1 reorganization in patients with stroke. Methods. Six patients with chronic stroke participated in the study. Patients executed robot-assisted wrist extension movements at 0.2 Hz frequency while subthreshold repetitive TMS was applied over M1 in a strict temporal relationship to the training movements. TMS was applied to either the affected hemisphere (contralateral M1) or the nonaffected hemisphere (ipsilateral M1) at 0.1 Hz. Intervention-related changes in motor maps and intracortical excitability were measured using TMS. Results. Training alone or combined Hebbian-type stimulation of either M1 resulted in differential effects on motor maps and intracortical inhibition. Shifts in motor maps were associated with increases in intracortical excitability. In contrast to previous results for healthy participants, the inhibitory effect of ipsilateral M1 Hebbian-type stimulation was not present, and the facilitatory effect of contralateral M1 stimulation was more subtle. Conclusions. Hebbian-type stimulation is feasible in patients poststroke and induces map reorganization and associated decreases in GABAergic inhibition. However, because TMS protocols have a different effect on motor reorganization in the injured brain and may depend on location of the lesion, protocols need to be tailored to the patient’s pathology.
Combined aliskiren-amlodipine treatment for hypertension in African Americans: clinical science and management issues
Authors: Izzo Joseph L. , Zion Adrienne S.
Published: May 2011

While it may seem at first that antihypertensive drug combinations run counter to the desire to ‘personalize’ the management of hypertension, the best combinations have predictable efficacy in different individuals and subpopulations. Race is probably not a valid surrogate for clinically meaningful genetic variation or guide to therapy. Most guidelines suggest similar blood pressure goals for different races but drug treatment recommendations have diverged. In the United States, race is not considered to be a major factor in drug choice, but in England and other countries, initial therapy with renin–angiotensin system blocking drugs is not recommended in Blacks. In this review we: (1) examine new trends in race-based research; (2) emphasize the weaknesses of race-based treatment recommendations; and (3) explore the effects of a new combination, renin inhibition (aliskiren) and amlodipine, in African Americans.
Obesity and bariatrics for the endoscopist: new techniques
Authors: Dayyeh Barham K. Abu , Thompson Christopher C.
Published: May 2011

Obesity and its associated conditions, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions. Gastrointestinal weight loss surgery (GIWLS) shows the most promise in achieving significant and sustained weight loss and diabetes resolution. However, a large mismatch exists between the magnitude of the obesity epidemic and the number of surgical procedures performed to produce a significant shift in the distribution of obesity on a population level. This mismatch is fueled by high surgical costs, morbidity and mortality associated with surgical interventions, and the fact that the greatest public health burden of obesity comes from those around the center of the population body mass index distribution with mild to moderate obesity, rather than those at the distribution tail with severe obesity that GIWLS targets. New endoscopic methods, capitalizing on advances in our understanding of the physiological mechanisms by which GIWLS works, are developing to provide viable alternatives in the treatment of bariatric surgical complications, and for the primary treatment of obesity. These methods may have the added advantage of reduced invasiveness, reversibility, cost-effectiveness, and applicability to a larger segment of the population with moderate obesity.
Gatekeeping at the Portal
Authors: Cleary Johanna , Bloom Terry
Published: May 2011

A content analysis of 353 local television station websites found 49.6% of stations are including user-generated content (UGC), mostly designed to capture eyeballs, rather than to engage citizens in the journalistic process. The user-generated material included video (50.9%), audio (14.3%), still photos (82.3%), and other content (13.7%) including blogs, event announcements, news tips, and viewer comments. The overwhelming majority (76%) of UGC focused on weather-related events with only 17.7% classified as breaking news. Editorial guidelines focused on legalities such as terms of use and privacy policies related to accepting content, not editorial standards. Gatekeeping theory was applied to find that the local press largely retains its traditional editorial function.
Steam as the working fluid for power recovery from exhaust gases by means of screw expanders
Authors: Smith I K , Stosic N , Mujic E , Kovacevic A
Published: May 2011

Rankine cycle systems, using steam as a working fluid, are not well suited to the recovery of power from heat sources in the 300–450 °C temperature range, such as internal combustion engine exhaust gases, mainly due to the relatively large enthalpy of vaporization of water. Admitting the steam to the expander as vapour approximately 50 per cent dry, would be preferable but turbines cannot be used to expand vapours from this state. However, screw expanders can operate well in this mode. It is shown that, apart from being environmentally benign and free from flammability risks, a screw-driven wet steam cycle system can recover power from engine exhaust gases, with comparable efficiencies to turbine-driven systems using organic fluids at a significantly lower cost per unit output.
Notch-Hes1 pathway is required for the development of IL-17–producing γδ T cells
Authors: Shibata Kensuke , Yamada Hisakata , Sato Tetsuya , Dejima Takashi , Nakamura Masataka , Ikawa Tomokatsu , Hara Hiromitsu , Yamasaki Sho , Kageyama Ryoichiro , Iwakura Yoichiro , Kawamoto Hiroshi , Toh Hiroyuki , Yoshikai Yasunobu
Published: May 2011

Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17–producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17–producing γδ T cells. Hes1 is critically involved in the development of IL-17–producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)–expressing stromal cells support the development of IL-17–producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17–producing γδ T cells.
25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients
Authors: Wasse Haimanot , Cardarelli Francesca , De Staercke Christine , Hooper Craig , Veledar Emir , Guessous Idris
Published: May 2011

Background

Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.

Methods

We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.

Results

Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).

Conclusions

Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.
Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modeling Approach
Authors: Munts Alexander G , Mugge Winfred , Meurs Thomas S , Schouten Alfred C , Marinus Johan , Moseley G Lorimer , van der Helm Frans CT , van Hilten Jacobus J
Published: May 2011

Background

Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. Involvement of dysfunctional GABAergic interneurons has been suggested, however the mechanisms that underpin fixed dystonia are still unknown. We hypothesized that dystonia could be the result of aberrant proprioceptive reflex strengths of position, velocity or force feedback.

Methods

We systematically characterized the pattern of dystonia in 85 CRPS-patients with dystonia according to the posture held at each joint of the affected limb. We compared the patterns with a neuromuscular computer model simulating aberrations of proprioceptive reflexes. The computer model consists of an antagonistic muscle pair with explicit contributions of the musculotendinous system and reflex pathways originating from muscle spindles and Golgi tendon organs, with time delays reflective of neural latencies. Three scenarios were simulated with the model: (i) increased reflex sensitivity (increased sensitivity of the agonistic and antagonistic reflex loops); (ii) imbalanced reflex sensitivity (increased sensitivity of the agonistic reflex loop); (iii) imbalanced reflex offset (an offset to the reflex output of the agonistic proprioceptors).

Results

For the arm, fixed postures were present in 123 arms of 77 patients. The dominant pattern involved flexion of the fingers (116/123), the wrists (41/123) and elbows (38/123). For the leg, fixed postures were present in 114 legs of 77 patients. The dominant pattern was plantar flexion of the toes (55/114 legs), plantar flexion and inversion of the ankle (73/114) and flexion of the knee (55/114).

Only the computer simulations of imbalanced reflex sensitivity to muscle force from Golgi tendon organs caused patterns that closely resembled the observed patient characteristics. In parallel experiments using robot manipulators we have shown that patients with dystonia were less able to adapt their force feedback strength.

Conclusions

Findings derived from a neuromuscular model suggest that aberrant force feedback regulation from Golgi tendon organs involving an inhibitory interneuron may underpin the typical fixed flexion postures in CRPS patients with dystonia.
Cost-effectiveness of early detection of breast cancer in Catalonia (Spain)
Authors: Carles Misericordia , Vilaprinyo Ester , Cots Francesc , Gregori Aleix , Pla Roger , Román Rubén , Sala Maria , Macià Francesc , Castells Xavier , Rue Montserrat
Published: May 2011

Background

Breast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care.

Methods

We used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios.

Results

Strategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY.

Conclusions

A reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area.
Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study
Authors: Chan Johnny YC , Tian Linwei , Kwan YW , Chan WM , Leung CW
Published: May 2011

Background

Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors.

Methods

The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach.

Results

During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month.

Conclusions

Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong.
Weight gain and incident obesity among male snus users
Authors: Hansson Jenny , Galanti Maria Rosaria , Magnusson Cecilia , Hergens Maria-Pia
Published: May 2011

Background

Snus is a moist smokeless tobacco product which has recently reached beyond its original market of Scandinavia. Snus is now being increasingly used in both the United States and South Africa. The effect of snus use on weight is unknown. This study has therefore investigated the relationship between the use of snus, weight gain (≥5%) and the incidence of obesity (body mass index ≥30 kg/m2).

Methods

The study participants (n = 9,954 males living in Stockholm County, Sweden) were recruited in 2002 and reassessed in 2007. Tobacco use was categorized according to information obtained in both the baseline and follow-up surveys. Outcomes were assessed by comparing self-reported weight and body mass index between the baseline and follow-up surveys.

Results

Stable current snus use (according to both surveys), compared to never having used any kind of tobacco, seemed to be associated with both weight gain (odds ratio = 1.31, 95% confidence interval: 1.04-1.65) and incident obesity (odds ratio = 1.93, 95% confidence interval: 1.13-3.30) after adjustment for age, baseline weight, alcohol consumption, physical activity, education, consumption of fruit and berries, and the frequency of having breakfast. No associations with incident obesity or weight gain were seen for stable former users of snus (according to both surveys) or among men who quit or began using snus during follow-up.

Conclusions

These data suggest that the use of snus is moderately associated with weight gain and incident obesity among men.
Factors related to knowledge and perception of women about smoking: a cross sectional study from a developing country
Authors: Bhanji Seema , Andrades Marie , Taj Fawad , Khuwaja Ali K
Published: May 2011

Background

Smoking rates among women are currently low, but they are the fastest growing segment of cigarette smoking population in developing countries. We aimed to assess the knowledge and perceptions towards smoking and to identify the factors related with level of knowledge and perceptions among adult women in urban slums.

Methods

This was a cross sectional study conducted on 250 adult (≥18 years of age) women attending primary care clinics in three slums of Karachi, Pakistan. A pre-tested and structured, interviewer administered questionnaire was used for data collection. Factors associated with level of understanding about smoking were analyzed with chi-square test.

Results

Most of the women knew that smoking has adverse effects on women and children's health but the knowledge of specific health effects was limited. About one third of the women knew that active smoking can cause lung disease, but only a small percentage (7%) knew that it could lead to heart disease. None of the women were aware that smoking contributes to infertility and osteoporosis. A small proportion of women were aware that smoking can lead to low birth weight (7%), congenital anomalies (5%) and less than 1% of women knew that it contributes to pregnancy loss, still birth and preterm delivery. The understanding of passive smoking affecting children's lung was low (20%) and a similar proportion voiced concern about the bad influence of maternal smoking on children. Educated women had better knowledge of health effects of smoking. Education was associated with having better knowledge about effects on women health in general (p = 0.02) and specific effects like lung (p = 0.03) and reproductive health effects (p < 0.001). Education was also associated with knowledge regarding effects on fetus (p < 0.001) and children (p < 0.005). Although most of the women disliked being around smokers, more than one third thought that smoking decreases boredom (39%), tension (38%) and also helps to relax (40%). A large proportion (48%) of women had the misconception that smoking helps to reduce weight.

Conclusions

This study reveals that women are aware of the general ill effects of smoking but fail to identify smoking to be associated with female maladies particularly those who were illiterate and had lower levels of education. Understanding and attitudes needs to be improved by increasing health awareness and education of women in these urban communities with special emphasis on the effects of smoking on women's health.
A reduction of CETP activity, not an increase, is associated with modestly impaired postprandial lipemia and increased HDL-Cholesterol in adult asymptomatic women
Authors: Parra Eliane S , Urban Aline , Panzoldo Natalia B , Nakamura Rui T , Oliveira Rogério , de Faria Eliana C
Published: May 2011

Background

The relationship between CETP and postprandial hyperlipemia is still unclear. We verified the effects of varying activities of plasma CETP on postprandial lipemia and precocious atherosclerosis in asymptomatic adult women.

Methods

Twenty-eight women, selected from a healthy population sample (n = 148) were classified according to three CETP levels, all statistically different: CETP deficiency (CETPd ≤ 4.5%, n = 8), high activity (CETPi ≥ 23.8, n = 6) and controls (CTL, CETP ≥ 4.6% and ≤ 23.7%, n = 14). After a 12 h fast they underwent an oral fat tolerance test (40 g of fat/m2 of body surface area) for 8 hours. TG, TG-rich-lipoproteins (TRL), cholesterol and TRL-TG measurements (AUC, AUIC, AR, RR and late peaks) and comparisons were performed on all time points. Lipases and phospholipids transfer protein (PLTP) were determined. Correlation between carotid atherosclerosis (c-IMT) and postprandial parameters was determined. CETP TaqIB and I405V and ApoE-ε3/ε2/ε4 polymorphisms were examined. To elucidate the regulation of increased lipemia in CETPd a multiple linear regression analysis was performed.

Results

In the CETPi and CTL groups, CETP activity was respectively 9 and 5.3 higher compared to the CETPd group. Concentrations of all HDL fractions and ApoA-I were higher in the CETPd group and clearance was delayed, as demonstrated by modified lipemia parameters (AUC, AUIC, RR, AR and late peaks and meal response patterns). LPL or HL deficiencies were not observed. No genetic determinants of CETP deficiency or of postprandial lipemia were found. Correlations with c-IMT in the CETPd group indicated postprandial pro-atherogenic associations. In CETPd the regression multivariate analysis (model A) showed that CETP was largely and negatively predicted by VLDL-C lipemia (R2 = 92%) and much less by TG, LDL-C, ApoAI, phospholipids and non-HDL-C. CETP (model B) influenced mainly the increment in ApoB-100 containing lipoproteins (R2 = 85% negatively) and phospholipids (R2 = 13%), at the 6thh point.

Conclusion

The moderate CETP deficiency phenotype included a paradoxically high HDL-C and its sub fractions (as earlier described), positive associations with c-IMT, a postprandial VLDL-C increment predicting negatively CETP activity and CETP activity regulating inversely the increment in ApoB100-containing lipoproteins. We hypothesize that the enrichment of TG content in triglyceride-rich ApoB-containing lipoproteins and in TG rich remnants increases lipoproteins' competition to active lipolysis sites,reducing their catabolism and resulting on postprandial lipemia with atherogenic consequences.
Anchored FRET sensors detect local caspase activation prior to neuronal degeneration
Authors: Figueroa Ricardo A , Ramberg Veronica , Gatsinzi Tom , Samuelsson Malin , Zhang Mu , Iverfeldt Kerstin , Hallberg Einar
Published: May 2011

Background

Recent studies indicate local caspase activation in dendrites or axons during development and in neurodegenerative disorders such as Alzheimer's disease (AD). Emerging evidences point to soluble oligomeric amyloid-β peptide as a causative agent in AD.

Results

Here we describe the design of fluorescence resonance energy transfer (FRET)-based caspase sensors, fused to the microtubule associated protein tau. Specific caspase sensors preferentially cleaved by caspase-3, -6 or -9 were expressed in differentiated human neuroblastoma SH-SY5Y cells. The anchoring of the sensors resulted in high FRET signals both in extended neurites and soma and made analysis of spatiotemporal signal propagation possible. Caspase activation was detected as loss of FRET after exposure to different stimuli. Interestingly, after staurosporine treatment caspase-6 activation was significantly delayed in neurites compared to cell bodies. In addition, we show that exposure to oligomer-enriched amyloid-β peptide resulted in loss of FRET in cells expressing sensors for caspase-3 and -6, but not -9, in both soma and neurites before neurite degeneration was observed.

Conclusions

Taken together, the results show that by using anchored FRET sensors it is possible to detect stimuli-dependent differential activation of caspases and to distinguish local from global caspase activation in live neuronal cells. Furthermore, in these cells oligomer-enriched amyloid-β peptide induces a global, rather than local activation of caspase-3 and -6, which subsequently leads to neuronal cell death.
Investigation of tension wood formation and 2,6-dichlorbenzonitrile application in short rotation coppice willow composition and enzymatic saccharification
Authors: Brereton Nicholas JB , Pitre Frederic E , Ray Michael J , Karp Angela , Murphy Richard J
Published: May 2011

Background

Short rotation coppice willow is a potential lignocellulosic feedstock in the United Kingdom and elsewhere; however, research on optimising willow specifically for bioethanol production has started developing only recently. We have used the feedstock Salix viminalis × Salix schwerinii cultivar 'Olof' in a three-month pot experiment with the aim of modifying cell wall composition and structure within the stem to the benefit of bioethanol production. Trees were treated for 26 or 43 days with tension wood induction and/or with an application of the cellulose synthesis inhibitor 2,6-dichlorobenzonitrile that is specific to secondary cell walls. Reaction wood (tension and opposite wood) was isolated from material that had received the 43-day tension wood induction treatment.

Results

Glucan content, lignin content and enzymatically released glucose were assayed. All measured parameters were altered without loss of total stem biomass yield, indicating that enzymatic saccharification yield can be enhanced by both alterations to cell wall structure and alterations to absolute contents of either glucan or lignin.

Conclusions

Final glucose yields can be improved by the induction of tension wood without a detrimental impact on biomass yield. The increase in glucan accessibility to cell wall degrading enzymes could help contribute to reducing the energy and environmental impacts of the lignocellulosic bioethanol production process.
Lineage relationship of prostate cancer cell types based on gene expression
Authors: Pascal Laura E , Vêncio Ricardo ZN , Vessella Robert L , Ware Carol B , Vêncio Eneida F , Denyer Gareth , Liu Alvin Y
Published: May 2011

Background

Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.

Methods

Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.

Results

Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.

Conclusions

Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.
Clinical utility of tibial motor and sensory nerve conduction studies with motor recording from the flexor hallucis brevis: a methodological and reliability study
Authors: Galloway Kathleen M , Lester Mark E , Evans Rachel K
Published: May 2011

Background

Standard tibial motor nerve conduction measures are established with recording from the abductor hallucis. This technique is often technically challenging and clinicians have difficulty interpreting the information particularly in the short segment needed to assess focal tibial nerve entrapment at the medial ankle as occurs in posterior tarsal tunnel syndrome. The flexor hallucis brevis (FHB) has been described as an alternative site for recording tibial nerve function in those with posterior tarsal tunnel syndrome. Normative data has not been established for this technique. This pilot study describes the technique in detail. In addition we provide reference values for medial and lateral plantar orthodromic sensory measures and assessed intrarater reliability for all measures.

Methods

Eighty healthy female participants took part, and 39 returned for serial testing at 4 time points. Mean values ± SD were recorded for nerve conduction measures, and coefficient of variation as well as intraclass correlation coefficients (ICC) were calculated.

Results

Motor latency, amplitude and velocity values for the FHB were 4.1 ± 0.9 msec, 8.0 ± 3.0 mV and 45.6 ± 3.4 m/s, respectively. Sensory latencies, amplitudes, and velocities, respectively, were 2.8 ± 0.3 msec, 26.7 ± 10.1 μV, and 41.4 ± 3.5 m/s for the medial plantar nerve and 3.2 ± 0.5 msec, 13.3 ± 4.7 μV, and 44.3 ± 4.0 msec for the lateral plantar nerve. All values demonstrated significant ICC values (P ≤ 0.007).

Conclusion

Motor recording from the FHB provides technically clear waveforms that allow for an improved ability to assess tibial nerve function in the short segments used to assess tarsal tunnel syndrome. The reported means will begin to establish normal values for this technique.
SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer
Authors: Yang Ming , Xie Wanling , Mostaghel Elahe , Nakabayashi Mari , Werner Lillian , Sun Tong , Pomerantz Mark , Freedman Matthew , Ross Robert , Regan Meredith , Sharifi Nima , Figg William Douglas , Balk Steven , Brown Myles , Taplin Mary-Ellen , Oh William K. , Lee Gwo-Shu Mary , Kantoff Philip W.
Published: May 2011

Purpose

Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT.

Patients and Methods

A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays.

Results

Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (Pinteraction = .041).

Conclusion

Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.
Activity of XL184 (Cabozantinib), an Oral Tyrosine Kinase Inhibitor, in Patients With Medullary Thyroid Cancer
Authors: Kurzrock Razelle , Sherman Steven I. , Ball Douglas W. , Forastiere Arlene A. , Cohen Roger B. , Mehra Ranee , Pfister David G. , Cohen Ezra E.W. , Janisch Linda , Nauling Forlisa , Hong David S. , Ng Chaan S. , Ye Lei , Gagel Robert F. , Frye John , Müller Thomas , Ratain Mark J. , Salgia Ravi
Published: May 2011

Purpose

XL184 (cabozantinib) is a potent inhibitor of MET, vascular endothelial growth factor receptor 2 (VEGFR2), and RET, with robust antiangiogenic, antitumor, and anti-invasive effects in preclinical models. Early observations of clinical benefit in a phase I study of cabozantinib, which included patients with medullary thyroid cancer (MTC), led to expansion of an MTC-enriched cohort, which is the focus of this article.

Patients and Methods

A phase I dose-escalation study of oral cabozantinib was conducted in patients with advanced solid tumors. Primary end points included evaluation of safety, pharmacokinetics, and maximum-tolerated dose (MTD) determination. Additional end points included RECIST (Response Evaluation Criteria in Solid Tumors) response, pharmacodynamics, RET mutational status, and biomarker analyses.

Results

Eighty-five patients were enrolled, including 37 with MTC. The MTD was 175 mg daily. Dose-limiting toxicities were grade 3 palmar plantar erythrodysesthesia (PPE), mucositis, and AST, ALT, and lipase elevations and grade 2 mucositis that resulted in dose interruption and reduction. Ten (29%) of 35 patients with MTC with measurable disease had a confirmed partial response. Overall, 18 patients experienced tumor shrinkage of 30% or more, including 17 (49%) of 35 patients with MTC with measurable disease. Additionally, 15 (41%) of 37 patients with MTC had stable disease (SD) for at least 6 months, resulting in SD for 6 months or longer or confirmed partial response in 68% of patients with MTC.

Conclusion

Cabozantinib has an acceptable safety profile and is active in MTC. Cabozantinib may provide clinical benefit by simultaneously targeting multiple pathways of importance in MTC, including MET, VEGFR2, and RET. A global phase III pivotal study in MTC is ongoing ( ClinicalTrials.gov number NCT00215605).
Persistent, Biologically Meaningful Prostate Cancer After 1 Year of Androgen Ablation and Docetaxel Treatment
Authors: Tzelepi Vassiliki , Efstathiou Eleni , Wen Sijin , Troncoso Patricia , Karlou Maria , Pettaway Curtis A. , Pisters Louis L. , Hoang Anh , Logothetis Christopher J. , Pagliaro Lance C.
Published: May 2011

Purpose

Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment.

Patients and Methods

Patients with locally advanced or lymph node–metastatic prostate cancer underwent 1 year of androgen ablation and three cycles of docetaxel therapy, followed by prostatectomy. All specimens were characterized for stage by accepted criteria. Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high-grade prostate cancer. Marker expression was divided into three groups: intracellular signaling pathways, stromal-epithelial interaction pathways, and angiogenesis.

Results

Forty patients were enrolled, 30 (75%) of whom underwent prostatectomy and two (5%) who underwent cystoprostatectomy. Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray. Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modulations of the insulin-like growth factor I pathway.

Conclusion

A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression.
Association Between Prescription Co-Payment Amount and Compliance With Adjuvant Hormonal Therapy in Women With Early-Stage Breast Cancer
Authors: Neugut Alfred I. , Subar Milayna , Wilde Elizabeth Ty , Stratton Scott , Brouse Corey H. , Hillyer Grace Clarke , Grann Victor R. , Hershman Dawn L.
Published: May 2011

Purpose

Noncompliance with adjuvant hormonal therapy among women with breast cancer is common. Little is known about the impact of financial factors, such as co-payments, on noncompliance.

Patients and Methods

We conducted a retrospective cohort study by using the pharmacy and medical claims database at Medco Health Solutions. Women older than age 50 years who were taking aromatase inhibitors (AIs) for resected breast cancer with two or more mail-order prescriptions, from January 1, 2007, to December 31, 2008, were identified. Patients who were eligible for Medicare were analyzed separately. Nonpersistence was defined as a prescription supply gap of more than 45 days without subsequent refill. Nonadherence was defined as a medication possession ratio less than 80% of eligible days.

Results

Of 8,110 women younger than age 65 years, 1,721 (21.1%) were nonpersistent and 863 (10.6%) were nonadherent. Among 14,050 women age 65 years or older, 3,476 (24.7%) were nonpersistent and 1,248 (8.9%) were nonadherent. In a multivariate analysis, nonpersistence (ever/never) in both age groups was associated with older age, having a non-oncologist write the prescription, and having a higher number of other prescriptions. Compared with a co-payment of less than $30, a co-payment of $30 to $89.99 for a 90-day prescription was associated with less persistence in women age 65 years or older (odds ratio [OR], 0.69; 95% CI, 0.62 to 0.75) but not among women younger than age 65, although a co-payment of more than $90 was associated with less persistence both in women younger than age 65 (OR, 0.82; 95% CI, 0.72 to 0.94) and those age 65 years or older (OR, 0.72; 95% CI, 0.65 to 0.80). Similar results were seen with nonadherence.

Conclusion

We found that higher prescription co-payments were associated with both nonpersistence and nonadherence to AIs. This relationship was stronger in older women. Because noncompliance is associated with worse outcomes, future policy efforts should be directed toward interventions that would help patients with financial difficulties obtain life-saving medications.