bluuebunny/crossref_metadata_2025 huggingface dataset:
Remodeling of the Cardiac Pacemaker L-Type Calcium Current and Its β-Adrenergic Responsiveness in Hypertension After Neuronal NO Synthase Gene Transfer
Authors: Heaton Daniel A. , Lei Ming , Li Dan , Golding Simon , Dawson Tom A. , Mohan Ravi M. , Paterson David J.
Published: July 2006

Hypertension is associated with abnormal neurohumoral activation. We tested the hypothesis that β-adrenergic hyperresponsiveness in the sinoatrial node (SAN) of the spontaneously hypertensive rat occurs at the level of the L-type calcium current because of altered cyclic nucleotide-dependent signaling. Furthermore, we hypothesized that NO, a modulator of cGMP and cAMP, would normalize the β-adrenergic phenotype in the hypertensive rat. Chronotropic responsiveness to norepinephrine (NE), together with production of cAMP and cGMP, was assessed in isolated atrial preparations from age-matched hypertensive and normotensive rats. Right atrial/SAN pacemaking tissue was injected with adenovirus encoding enhanced green fluorescent protein (control vector) or neuronal NO synthase (nNOS). In addition, L-type calcium current was measured in cells isolated from the SAN of transfected animals. Basal levels of cGMP were lower in hypertensive rat atria. These atria were hyperresponsive to NE at all of the concentrations tested, with elevated production of cAMP. This was accompanied by increased basal and norepinephrine-stimulated L-type calcium current. Using enhanced green fluorescent protein, we observed transgene expression within both tissue sections and isolated pacemaking cells. Adenoviral nNOS increased right atrial nNOS protein expression and cGMP content. NE-stimulated cAMP concentration and L-type calcium current were also attenuated by adenoviral nNOS, along with the chronotropic responsiveness to NE in hypertensive rat atria. Decreased calcium current after cardiac nNOS gene transfer contributes to the normalization of β-adrenergic hyperresponsiveness in the SAN from hypertensive rats by modulating cyclic nucleotide signaling.
C-Reactive Protein Upregulates Receptor for Advanced Glycation End Products Expression in Human Endothelial Cells
Authors: Zhong Yun , Li Shu-Hong , Liu Shi-Ming , Szmitko Paul E. , He Xiao-Qing , Fedak Paul W.M. , Verma Subodh
Published: July 2006

The receptor for advanced glycation end products (RAGE) may play an important role in inflammatory processes and endothelial activation, likely to accelerate the processes of coronary atherosclerotic development, especially in diabetic patients. The factors that regulate arterial expression of RAGE are not completely clear. C-reactive protein (CRP) is identified as a key proinflammatory cytokine in patients with atherosclerosis. Therefore, we tested the hypothesis that RAGE expression in endothelial cells can be upregulated by CRP. Human saphenous vein endothelial cells were incubated with human recombinant CRP, free of sodium azide and endotoxin. RAGE protein expression was measured by flow-cytometric analysis and Western blotting. CRP caused a significant increase in RAGE protein expression at a dose as low as 5 μg/mL, with expression peaking at 24 to 48 hours after CRP incubation. The effects of modified monomeric CRP on RAGE protein expression were comparable with that of native pentameric CRP. At the mRNA level, CRP not only increased RAGE gene expression but also attenuated the degradation of RAGE mRNA. Furthermore, RNA interference of RAGE gene expression significantly decreased the level of macrophage chemoattractant protein 1, a key downstream mediator of CRP activity. Therefore, CRP at concentrations known to predict future vascular events upregulates RAGE expression in human endothelial cells at both the protein and mRNA level. Silencing of the RAGE gene prevents CRP–induced macrophage chemoattractant protein 1 activation. These data reinforce the mechanistic links among inflammation, endothelial dysfunction, and atherothrombosis.
From Areopagus to Corinth (Acts 17:22–31; I Cor 2:1–5) A Study on the Transition from the Power of Knowledge to the Power of the Spirit
Authors: Pathrapankal Joseph
Published: July 2006

How are we to understand Christian mission in our time? Is it the obedient response to the commission of his disciples by Jesus after his resurrection (Mt 28:18–20)? What should be the motivating power behind the mission of the church? Is it patterned on the conquest expeditions of the people of Israel narrated in the Old Testament? The long history of the mission of the church, especially as organized by the West, would give us such an impression. This approach has more the nature of exercising power over the other, the power of knowledge and the power of self to win over the other. From the time of the Roman Emperor, Constantine, this had been the pattern in the history of the western church. But times have changed and there is a real shift in the understanding of Christian mission in the context of religious pluralism. The Bible itself seems to support and substantiate this change of perspective of understanding mission as the operation of the power of the Spirit of God. Taking two New Testament writings, the Acts of the Apostles and the first Letter to the Corinthians as paradigms, the author tries to see how Paul first of all attempted to preach the gospel in Athens with the eloquence and wisdom of the Greeks and then changed his approach in Corinth to give centrality to the power of the Spirit of God. Although we may not argue for a historical sequence for this change of attitude in the case of Paul, applying new developments in biblical interpretation, we can still propose it as a trans-textual approach with a message for our time. The Word of God has within itself a dynamism to take on new meanings and new horizons of ideas through its encounter with new contexts in a pluralistic world.
A Multilevel Factor Model for Mixed Binary and Ordinal Indicators of Women's Status
Authors: Steele Fiona , Goldstein Harvey
Published: July 2006

The authors present a factor model for the analysis of categorical responses with a two-level hierarchical structure. The model allows for multiple, potentially correlated factors at each level as well as covariate effects on the responses. Estimation using Markov chain Monte Carlo (MCMC) methods is described. The methodology is applied in an analysis of women's status in Bangladesh. Two dimensions of women's status are considered—social independence and decision-making power—and the factor structure of the responses at the woman and district levels is explored.
Investigating the Variation of Personal Network Size Under Unknown Error Conditions
Authors: Killworth Peter D. , McCarty Christopher , Johnsen Eugene C. , Bernard H. Russell , Shelley Gene A.
Published: July 2006

This article estimates the variation in personal network size, using respondent data containing two systematic sources of error. The data are the proportion of respondents who, on average, claim to know zero, one, and two people in various subpopulations, such as “people who are widows under the age of 65” or “people who are diabetics.” The two kinds of error—transmission error (respondents are unaware that someone in their network is in a subpopulation) and barrier error (something causes a respondent to know more or less than would be expected, in a subpopulation)—are hard to quantify. The authors show how to estimate the shape of the probability density function (pdf) of the number of people known to a random individual by assuming that respondents give what they assume to be accurate responses based on incorrect knowledge. It is then possible to estimate the relative effective sizes of subpopulations and produce an internally consistent theory. These effective sizes permit an evaluation of the shape of the pdf, which, remarkably, agrees with earlier estimates.
A total entropy model of spatial data uncertainty
Authors: Shi Y. F. , Jin F. X. , Li M. Y.
Published: July 2006

Uncertainty is inherent in spatial data and spatio-temporal phenomena. Spatial data uncertainty generally refers to error, inexactness, fuzziness and ambiguity. The goals of research on spatial data uncertainty are to investigate how uncertainties arise, or are created and propagated in the spatial data process. Based on information theory, considering the characteristics of randomicity of positional data and fuzziness of attribute data and taking entropy as a measure, this paper proposes the stochastic entropy model of spatial positional data uncertainty and fuzzy entropy model of spatial attribute data uncertainty. Usually, both randomicity and fuzziness exist in spatial data simultaneously, so their co-uncertainty is also investigated and quantified in this paper. A novel spatial data uncertainty measure, total entropy, is presented. Total entropy can be used as a uniform measure to quantify the total spatial data uncertainty caused by stochastic uncertainty and fuzzy uncertainty.
Institutional addresses in the Web of Science: the effects on scientific evaluation
Authors: García-Zorita Carlos , Martín-Moreno Carmen , Lascurain-Sánchez M. Luisa , Sanz-Casado Elías
Published: July 2006

The effectiveness of the analytical tools used for the evaluation of scientific activity has been enhanced by the availability of bibliographic databases, in particular the standard-setting Institute for Scientific Information databases, whose operating rules are widely accepted by the scientific community. One of these rules is the availability in a single field of the institutional affiliations of all the authors of a paper. In practice this rule has been replaced by another, resulting from the inclusion of a new option, whereby records can be retrieved by the author’s reprint address (Reprint Address field). The outcome is diversity in the information on affiliation that may generate some degree of uncertainty in connection with institutional attribution when discrepancies arise between the information contained in the two fields, mainly when the only option available is the reprint address. The present study found a high degree of uncertainty, however, essentially for the period prior to Web of Science, in particular for scientific evaluation in peripheral countries such as Spain.
Income Diversification in Norwegian Farm Households
Authors: Rønning Lars , Kolvereid Lars
Published: July 2006

Many farm households rely on income from multiple sources, a phenomenon known as pluriactivity. The present survey investigates whether this is a deliberate strategy rather than a situation forced upon the farm household by external conditions. This study explores the relationship between four income diversification strategies reported by farmers and household income. Data from a representative random sample of 901 Norwegian farm households is analysed using multiple regression. External employment and holding additional non-farm-related businesses is significantly positively related to household income. This shows that diversification into other economic sectors has a positive effect on income. Moreover, diversification within the farm sector has no effect on household income. The findings imply that future policy should consider pluriactivity as a deliberate strategy contributing to farm family wealth.
Smart Rehabilitation Devices: Part II – Adaptive Motion Control
Authors: Dong Shufang , Lu Ke–Qian , Sun J. Q. , Rudolph Katherine
Published: July 2006

This article presents a study of adaptive motion control of smart versatile rehabilitation devices using MR fluids. The device provides both isometric and isokinetic strength training and is reconfigurable for several human joints. Adaptive controls are developed to regulate resistance force based on the prescription of the therapist. Special consideration has been given to the human–machine interaction in the adaptive control that can modify the behavior of the device to account for strength gains or muscle fatigue of the human subject.
Statistical Analysis of Terfenol-D Material Properties
Authors: Dapino Marcelo J. , Flatau Alison B. , Calkins Frederick T.
Published: July 2006

This article focuses on the characterization of Terfenol-D material properties under magnetic bias, mechanical preloads, AC drive fields, frequencies of operation, and mechanical loads typical of many dynamic transducer applications. These are test conditions unlike those in most Terfenol-D characterization studies. The article also provides an explanation for prior experimental studies which suggest that significant variation in material properties are expected in Terfenol-D elements subjected to repeated tests under fixed operating conditions. Through a statistical framework for the design of experiments and data analysis, we conducted repeatability tests which demonstrate that such variations are likely to be due to imperfect control of the magnetic bias and mechanical preload from test to test, and not to intrinsic material behavior. Frequency response measurements from near DC to past the test transducer's fundamental frequency were combined with classical electroacoustics theory to determine the functional dependence of magnetoelastic properties with respect to varying operating regimes. These properties include two elastic moduli, piezomagnetic coefficient, magnetomechanical coupling coefficient, and two magnetic permeabilities. Analysis of variance (ANOVA) calculations were employed to determine 95% prediction and confidence intervals for the overall material property trends and coefficients of variation associated with the repeatability tests.
Social Capital Processes in Cross Cultural Management
Authors: Staber Udo
Published: July 2006

Many researchers in the area of cross cultural management follow a structuralist and static conception of the culture construct. In this article, I outline a critique of this approach to culture and offer the concept of social capital as a potential corrective to the limitations of the structuralist paradigm widely in use. The social capital approach treats social relations, rather than organizations or individuals, as the unit of analysis, and focuses on the processes and mechanisms by which social relations contribute to outcomes relevant to cross cultural management. I suggest a methodology for studying social capital as a network process, focusing on the connections between actions or events.
Response Styles in Cross-national Survey Research
Authors: Harzing Anne-Wil
Published: July 2006

Studies of attitudes across countries generally rely on a comparison of aggregated mean scores to Likert-scale questions. This presupposes that when people complete a questionnaire, their answers are based on the substantive meaning of the items to which they respond. However, people's responses are also influenced by their response style. Hence, the studies we conduct might simply reflect differences in the way people respond to surveys, rather than picking up real differences in management phenomena across countries. Our 26-country study shows that there are major differences in response styles between countries that both confirm and extend earlier research. Country-level characteristics such as power distance, collectivism, uncertainty avoidance and extraversion all significantly influence response styles such as acquiescence and extreme response styles. Further, English-language questionnaires are shown to elicit a higher level of middle responses, while questionnaires in a respondent's native language result in more extreme response styles. Finally, English-language competence is positively related to extreme response styles and negatively related to middle response styles. We close by discussing implications for cross-national research.
Leadership and Inequality
Authors: Harter Nathan , Ziolkowski Fred J. , Wyatt Stephanie
Published: July 2006

Ordinarily, a leader is perceived to be distinctive. Many images depict leaders as higher, larger, or further along toward some objective. In order to downplay the hierarchical implications of leadership, writers have made numerous attempts to introduce egalitarian values, since leadership itself can come across as unjust or unfair, contrary to an egalitarian ideal. The egalitarian will prefer an alternative, either an alternative to leadership altogether or an alternative image of leadership that suggests equality. We assert that there is a conceptual difference between leaders and followers. We also claim that inequality is inevitable, useful, and even necessary. Properly accounted for, inequality is also just - to elevate a single person to a position or status of leader, so long as that leadership enjoys legitimacy, dependent on purpose, and so long as that leadership remains subject to checks and balances. Maybe we need a model of leadership as mutual inequality.
The More Things Change, the More They Remain the Same? Evaluating Strategic Leadership in Organizational Transformations
Authors: Pajunen Kalle
Published: July 2006

This study considers what has changed in strategic leadership during the last century and if we could learn something from the past. These questions are addressed through an historical case analysis of a Finnish pulp and paper industry leader, Gösta Serlachius. The findings show that at the surface level the world of strategic leadership is likely to be transient and contingent, but at the deeper level it seems to be based on much more stable elements. A correct combination of absorptive and adaptive capacities merged with managerial wisdom provided the basis for effective strategic leadership at the beginning of the 20th century in a similar way as today. Indeed, the more things change, the more crucial is the combination of these basic elements matching with the organizational environment. It is concluded that historical studies can add substantially to the future strategic leadership research.
Getting the message? ‘New’ Labour and the criminalization of ‘hate’
Authors: Dixon Bill , Gadd David
Published: July 2006

Hate crimes, it has been said, are ‘message’ crimes to which society needs to respond using the most powerful and unambiguous means of communication at its disposal, the criminal law. Using empirical data collected in the course of research conducted by the authors on racially motivated violence and harassment in North Staffordshire, this article sets out to interpret the messages about hate crime sent to perpetrators, and people from their local communities, by the creation, in the Crime and Disorder Act 1998, of a new category of racially aggravated offences. To this end two possible anti-hate crime messages and three potential audiences are identified and evaluated in the light of data generated from biographical interviews with perpetrators and focus group discussions with other local people in and around the city of Stokeon-Trent. Our conclusion is that the supposedly clear deterrent and denunciatory or declaratory messages contained in the 1998 Act are either drowned out or distorted by other signals coming from successive ‘New’ Labour governments about crime, immigration, nationality and ‘community cohesion’, and by the highly idiosyncratic and unpredictable ways in which they are mediated and interpreted by their intended recipients.
Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke
Authors: Machado Livia S , Kozak Anna , Ergul Adviye , Hess David C , Borlongan Cesario V , Fagan Susan C
Published: July 2006

Background

Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are increased in the brain after experimental ischemic stroke in rats. These two proteases are involved with the degradation of the basal lamina and loss of stability of the blood brain barrier that occurs after ischemia and that is associated with thrombolytic therapy in ischemic stroke. Minocycline is a lipophilic tetracycline and is neuroprotective in several models of brain injury. Minocycline inhibits inflammation, apoptosis and extracellular matrix degradation. In this study we investigated whether delayed minocycline inhibits brain MMPs activated by ischemia in a model of temporary occlusion in Wistar rats.

Results

Both MMP-2 and MMP-9 were elevated in the ischemic tissue as compared to the contra-lateral hemisphere after 3 hours occlusion and 21 hours survival (p < 0.0001 for MMP-9). Intraperitoneal minocycline at 45 mg/kg concentration twice a day (first dose immediately after the onset of reperfusion) significantly reduced gelatinolytic activity of ischemia-elevated MMP-2 and MMP-9 (p < 0.0003). Treatment also reduced protein concentration of both enzymes (p < 0.038 for MMP-9 and p < 0.018 for MMP-2). In vitro incubation of minocycline in concentrations as low as 0.1 μg/ml with recombinant MMP-2 and MMP-9 impaired enzymatic activity and MMP-9 was more sensitive at lower minocycline concentrations (p < 0.05).

Conclusion

Minocycline inhibits enzymatic activity of gelatin proteases activated by ischemia after experimental stroke and is likely to be selective for MMP-9 at low doses. Minocycline is a potential new therapeutic agent to acute treatment of ischemic stroke.
The frequency of genes encoding three putative group B streptococcal virulence factors among invasive and colonizing isolates
Authors: Manning Shannon D , Ki Moran , Marrs Carl F , Kugeler Kiersten J , Borchardt Stephanie M , Baker Carol J , Foxman Betsy
Published: July 2006

Background

Group B Streptococcus (GBS) causes severe infections in very young infants and invasive disease in pregnant women and adults with underlying medical conditions. GBS pathogenicity varies between and within serotypes, with considerable variation in genetic content between strains. Three proteins, Rib encoded by rib, and alpha and beta C proteins encoded by bca and bac, respectively, have been suggested as potential vaccine candidates for GBS. It is not known, however, whether these genes occur more frequently in invasive versus colonizing GBS strains.

Methods

We screened 162 invasive and 338 colonizing GBS strains from different collections using dot blot hybridization to assess the frequency of bca, bac and rib. All strains were defined by serotyping for capsular type, and frequency differences were tested using the Chi square test.

Results

Genes encoding the beta C protein (bac) and Rib (rib) occurred at similar frequencies among invasive and colonizing isolates, bac (20% vs. 23%), and rib (28% vs. 20%), while the alpha (bca) C protein was more frequently found in colonizing strains (46%) vs, invasive (29%). Invasive strains were associated with specific serotype/gene combinations.

Conclusion

Novel virulence factors must be identified to better understand GBS disease.
An immune response in the bumblebee, Bombus terrestris leads to increased food consumption
Authors: Tyler Elizabeth R , Adams Sally , Mallon Eamonn B
Published: July 2006

Background

The concept of a costly immune system that must be traded off against other important physiological systems is fundamental to the burgeoning field of ecological immunity. Bumblebees have become one of the central models in this field. Although previous work has demonstrated costs of immunity in numerous life history traits, estimates of the more direct costs of bumblebee immunity have yet to be made.

Results

Here we show a 7.5% increase in energy consumption in response to non-pathogenic immune stimulation.

Conclusion

This increase in energy consumption along with other results suggests that immunity is one of the most important physiological systems, with other systems being sacrificed for its continuing efficiency. This increased consumption and maintained activity contrasts with the sickness-induced anorexia and reduced activity found in vertebrates.
A systematic review of complex system interventions designed to increase recovery from depression in primary care
Authors: Gunn Jane , Diggens Justine , Hegarty Kelsey , Blashki Grant
Published: July 2006

Background

Primary care is being encouraged to implement multiprofessional, system level, chronic illness management approaches to depression. We undertook this study to identify and assess the quality of RCTs testing system level depression management interventions in primary care and to determine whether these interventions improve recovery.

Method

Searches of Medline and Cochrane Controlled Register of Trials. 'System level' interventions included: multi-professional approach, enhanced inter-professional communication, scheduled patient follow-up, structured management plan.

Results

11 trials met all inclusion criteria. 10 were undertaken in the USA. Most focussed on antidepressant compliance. Quality of reporting assessed using CONSORT criteria was poor. Eight trials reported an increase in the proportion of patients recovered in favour of the intervention group, yet did not account for attrition rates ranging from 5 to 50%.

Conclusion

System level interventions implemented in the USA with patients willing to take anti-depressant medication leads to a modest increase in recovery from depression. The relevance of these interventions to countries with strong primary care systems requires testing in a randomised controlled trial.
Implementation of a structured paediatric admission record for district hospitals in Kenya – results of a pilot study
Authors: Mwakyusa Sekela , Wamae Annah , Wasunna Aggrey , Were Fred , Esamai Fabian , Ogutu Bernhards , Muriithi Assumpta , Peshu Norbert , English Mike
Published: July 2006

Background

The structured admission form is an apparently simple measure to improve data quality. Poor motivation, lack of supervision, lack of resources and other factors are conceivably major barriers to their successful use in a Kenyan public hospital setting. Here we have examined the feasibility and acceptability of a structured paediatric admission record (PAR) for district hospitals as a means of improving documentation of illness.

Methods

The PAR was primarily based on symptoms and signs included in the Integrated Management of Childhood Illness (IMCI) diagnostic algorithms. It was introduced with a three-hour training session, repeated subsequently for those absent, aiming for complete coverage of admitting clinical staff. Data from consecutive records before (n = 163) and from a 60% random sample of dates after intervention (n = 705) were then collected to evaluate record quality. The post-intervention period was further divided into four 2-month blocks by open, feedback meetings for hospital staff on the uptake and completeness of the PAR.

Results

The frequency of use of the PAR increased from 50% in the first 2 months to 84% in the final 2 months, although there was significant variation in use among clinicians. The quality of documentation also improved considerably over time. For example documentation of skin turgor in cases of diarrhoea improved from 2% pre-intervention to 83% in the final 2 months of observation. Even in the area of preventive care documentation of immunization status improved from 1% of children before intervention to 21% in the final 2 months.

Conclusion

The PAR was well accepted by most clinicians and greatly improved documentation of features recommended by IMCI for identifying and classifying severity of common diseases. The PAR could provide a useful platform for implementing standard referral care treatment guidelines.
Prevalence of diabetes and other cardiovascular risk factors in an Iranian population with acute coronary syndrome
Authors: Esteghamati Alireza , Abbasi Mehrshad , Nakhjavani Manouchehr , Yousefizadeh Abbas , Basa Amelita P , Afshar Hamid
Published: July 2006

Background

Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population.

Methods

The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows.

Results

Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 ± 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 ± 11.6 vs. 59.7 ± 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p <0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 ± 11.6 vs. 59.2 ± 13 years, p < 0.005) and had higher total serum cholesterol (200 ± 41.8 vs. 192 ± 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 ± 22 vs. 40 ± 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels).

Conclusion

In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease.
Non-differential measurement error does not always bias diagnostic likelihood ratios towards the null
Authors: Fosgate GT
Published: July 2006

Diagnostic test evaluations are susceptible to random and systematic error. Simulated non-differential random error for six different error distributions was evaluated for its effect on measures of diagnostic accuracy for a brucellosis competitive ELISA. Test results were divided into four categories: <0.25, 0.25 – 0.349, 0.35 – 0.499, and ≥ 0.50 proportions inhibition for calculation of likelihood ratios and diagnostic odds ratios. Larger variance components of the error structure resulted in larger accuracy attenuations as measured by the area under the receiver-operating characteristic curve and systematic components appeared to cause little bias. Added error caused point estimates of likelihood ratios to be biased towards the null value (1.0) for all categories except 0.25 – 0.349. Results for the 0.35 – 0.499 category also extended beyond the null value for some error structures. Diagnostic odds ratios were consistently biased towards the null when the <0.25 category was considered the reference level. Non-differential measurement error can lead to biased results in the quantitative evaluation of ELISA and the direction is not always towards the null value.
A radial basis classifier for the automatic detection of aspiration in children with dysphagia
Authors: Lee Joon , Blain Stefanie , Casas Mike , Kenny Dave , Berall Glenn , Chau Tom
Published: July 2006

Background

Silent aspiration or the inhalation of foodstuffs without overt physiological signs presents a serious health issue for children with dysphagia. To date, there are no reliable means of detecting aspiration in the home or community. An assistive technology that performs in these environments could inform caregivers of adverse events and potentially reduce the morbidity and anxiety of the feeding experience for the child and caregiver, respectively. This paper proposes a classifier for automatic classification of aspiration and swallow vibration signals non-invasively recorded on the neck of children with dysphagia.

Methods

Vibration signals associated with safe swallows and aspirations, both identified via videofluoroscopy, were collected from over 100 children with neurologically-based dysphagia using a single-axis accelerometer. Five potentially discriminatory mathematical features were extracted from the accelerometry signals. All possible combinations of the five features were investigated in the design of radial basis function classifiers. Performance of different classifiers was compared and the best feature sets were identified.

Results

Optimal feature combinations for two, three and four features resulted in statistically comparable adjusted accuracies with a radial basis classifier. In particular, the feature pairing of dispersion ratio and normality achieved an adjusted accuracy of 79.8 ± 7.3%, a sensitivity of 79.4 ± 11.7% and specificity of 80.3 ± 12.8% for aspiration detection. Addition of a third feature, namely energy, increased adjusted accuracy to 81.3 ± 8.5% but the change was not statistically significant. A closer look at normality and dispersion ratio features suggest leptokurticity and the frequency and magnitude of atypical values as distinguishing characteristics between swallows and aspirations. The achieved accuracies are 30% higher than those reported for bedside cervical auscultation.

Conclusion

The proposed aspiration classification algorithm provides promising accuracy for aspiration detection in children. The classifier is conducive to hardware implementation as a non-invasive, portable "aspirometer". Future research should focus on further enhancement of accuracy rates by considering other signal features, classifier methods, or an augmented variety of training samples. The present study is an important first step towards the eventual development of wearable intelligent intervention systems for the diagnosis and management of aspiration.
Four-year follow-up of infliximab therapy in rheumatoid arthritis patients with long-standing refractory disease: attrition and long-term evolution of disease activity
Authors: Cruyssen Bert Vander , Van Looy Stijn , Wyns Bart , Westhovens Rene , Durez Patrick , Van den Bosch Filip , Mielants Herman , De Clerck Luc , Peretz Ann , Malaise Michel , Verbruggen Leon , Vastesaeger Nathan , Geldhof Anja , Boullart Luc , De Keyser Filip
Published: July 2006

Although there is strong evidence supporting the short-term efficacy and safety of anti-tumour necrosis factor-α agents, few studies have examined the long-term effects. We evaluated 511 patients with long-standing refractory rheumatoid arthritis treated with intravenous infusions of infliximab 3 mg/kg at weeks 0, 2, 6, and 14 and every 8 weeks thereafter for 4 years. Among the initial 511 patients included in the study, 479 could be evaluated; of these, 295 (61.6%) were still receiving infliximab treatment at year 4 of follow-up. The most common reasons for treatment discontinuation were lack of efficacy (65 patients, 13.6%), safety (81 patients, 16.9%), and elective change (38 patients, 7.9%). Analysis of disease activity scores (DAS28 [disease activity score based on the 28-joint count]) over time showed that, after the initial rapid improvement during the first 6 to 22 weeks of therapy, a further decrease in disease activity of 0.2 units in the DAS28 score per year was observed. DAS28 scores, measured at week 14 or 22, were found to predict subsequent discontinuation due to lack of efficacy. In conclusion, long-term maintenance therapy with infliximab 3 mg/kg is effective in producing further reductions in disease activity. Disease activity measured by the DAS28 at week 14 or 22 of infliximab therapy was the best predictor of long-term attrition.
MUC1 alters oncogenic events and transcription in human breast cancer cells
Authors: Hattrup Christine L , Gendler Sandra J
Published: July 2006

Introduction

MUC1 is an oncoprotein whose overexpression correlates with aggressiveness of tumors and poor survival of cancer patients. Many of the oncogenic effects of MUC1 are believed to occur through interaction of its cytoplasmic tail with signaling molecules. As expected for a protein with oncogenic functions, MUC1 is linked to regulation of proliferation, apoptosis, invasion, and transcription.

Methods

To clarify the role of MUC1 in cancer, we transfected two breast cancer cell lines (MDA-MB-468 and BT-20) with small interfering (si)RNA directed against MUC1 and analyzed transcriptional responses and oncogenic events (proliferation, apoptosis and invasion).

Results

Transcription of several genes was altered after transfection of MUC1 siRNA, including decreased MAP2K1 (MEK1), JUN, PDGFA, CDC25A, VEGF and ITGAV (integrin αv), and increased TNF, RAF1, and MMP2. Additional changes were seen at the protein level, such as increased expression of c-Myc, heightened phosphorylation of AKT, and decreased activation of MEK1/2 and ERK1/2. These were correlated with cellular events, as MUC1 siRNA in the MDA-MB-468 line decreased proliferation and invasion, and increased stress-induced apoptosis. Intriguingly, BT-20 cells displayed similar levels of apoptosis regardless of siRNA, and actually increased proliferation after MUC1 siRNA.

Conclusion

These results further the growing knowledge of the role of MUC1 in transcription, and suggest that the regulation of MUC1 in breast cancer may be more complex than previously appreciated. The differences between these two cell lines emphasize the importance of understanding the context of cell-specific signaling events when analyzing the oncogenic functions of MUC1, and caution against generalizing the results of individual cell lines without adequate confirmation in intact biological systems.
A suppressive role of nitric oxide in MIP-2 production by macrophages upon coculturing with apoptotic cells
Authors: Shibata Takehiko , Nagata Kisaburo , Kobayashi Yoshiro
Published: July 2006

Macrophages phagocytose apoptotic cells without causing neutrophil infiltration in vivo under physiological conditions. Our recent study, however, showed that macrophages produce IL-8 or MIP-2, a murine IL-8 homologue, upon coculturing with apoptotic cells, indicating that there must be unknown mechanisms for preventing IL-8 or MIP-2 production. As activated macrophages produce NO to regulate inflammation, we examined the NO production by macrophages upon coculturing with apoptotic or necrotic cells and explored the role of NO in MIP-2 production. NO was produced on coculturing with early apoptotic cells much more significantly than with late apoptotic or necrotic cells. On the contrary, MIP-2 was produced on coculturing with late apoptotic or necrotic cells much more significantly than with early apoptotic cells. NG-Nitro-l-arginine methyl ester, an inhibitor of NO synthase, or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of NO, augmented MIP-2 production on coculturing with early apoptotic cells. The addition of N-ethylethanamine:1,1-diethyl-2-hydroxy-2-nitrosohydrazine [1:1], a donor of NO, conversely, caused suppression of MIP-2 production on coculturing with late apoptotic cells. These results suggest an important role of NO for preventing MIP-2 production by macrophages upon coculturing with early apoptotic cells.
Conservation Surgery for Breast Cancer As the Preferred Choice: A Prospective Analysis
Authors: Temple Walley J. , Russell Margaret L. , Parsons Louise L. , Huber Sylvia M. , Jones. Charlotte A. , Bankes Jane , Eliasziw Michael
Published: July 2006

Purpose

To describe the proportion of women who anticipate having breast-conserving surgery (BCS) versus modified radical mastectomy (MRM), the factors they considered when making treatment choices, the degree to which they perceived they had participated in and had control of the treatment decision, and to explore factors associated with type of planned surgery.

Patients and Methods

Prospective cohort study conducted among patients attending a tertiary care hospital in Alberta, Canada from 1992 to 1995. Participants had a first diagnosis of localized unilateral breast cancer, and were, in the opinions of their surgeons, candidates for either BCS or MRM.

Results

Of 157 participants, 71.3% anticipated having BCS and 28.7% anticipated MRM. Referents perceived to play an important role in decision making included self, doctor, and significant other. The two top-ranked items perceived to have influenced treatment choice were doctor's advice and possibility of complete cure. Most women (60%) participated in treatment choice to the degree that they preferred, but only 13.6% received their preferred amount of information. The type of planned surgery was predicted by surgeon, contribution of doctor to choice of treatment, importance of breasts to sexuality, self-efficacy, and concerns about cancer recurrence from a multivariable logistic regression model.

Conclusion

Both patient and surgeon factors are important predictors of type of planned surgery. There is a gap between women's preferences and actual experiences with regard to information provided and patient participation in treatment choices, with women’s desire for more information about their treatment being most prevalent.
Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients With Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial From the Cannabis-In-Cachexia-Study-Group
Authors: Strasser Florian , Luftner Diana , Possinger Kurt , Ernst Gernot , Ruhstaller Thomas , Meissner Winfried , Ko You-Dschun , Schnelle Martin , Reif Marcus , Cerny Thomas
Published: July 2006

Purpose

To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS).

Patients and Methods

Adult patients with advanced cancer, CACS, weight loss (≥ 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks.

Results

Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% ≥ 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms.

Conclusion

CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.
Lifestyle Intervention Development Study to Improve Physical Function in Older Adults With Cancer: Outcomes From Project LEAD
Authors: Demark-Wahnefried Wendy , Clipp Elizabeth C. , Morey Miriam C. , Pieper Carl F. , Sloane Richard , Snyder Denise Clutter , Cohen Harvey J.
Published: July 2006

Purpose

Declines in physical functioning (PF) among elderly cancer patients threaten quality of life and the ability to maintain independence. Adherence to healthy lifestyle behaviors may prevent functional decline.

Patients and Methods

Project Leading the Way in Exercise and Diet (LEAD), an intervention development study of the Pepper Older Americans Independence Center, aimed to determine whether breast and prostate cancer survivors (age 65+ years) assigned to a 6-month home-based diet and exercise intervention experienced improvements in PF when compared with an attention control arm receiving general health information. An accrual target was set at 420, and PF (Short Form-36 subscale), physical activity (Community Healthy Activities Models Program for Seniors), and diet quality (index from 3-day recalls) were assessed at baseline and at 6 and 12 months (6 months after intervention).

Results

This developmental project did not achieve its accrual target (N = 182); however, PF change scores were in the direction and of the magnitude projected. Baseline to 6-month change scores in the intervention versus the control arms were as follows: PF, +3.1 v −0.5 (P = .23); physical activity energy expenditure, +111 kcal/wk v −400 kcal/wk (P = .13); and diet quality index, +2.2 v −2.9 (P = .003), respectively. Differences between arms diminished during the postintervention period.

Conclusion

These findings suggest that home-based diet and exercise interventions hold promise in improving lifestyle behaviors among older cancer survivors, changes that trend toward improved PF. Future studies should incorporate larger sample sizes and interventions that sustain long-term effects and also take into account secular trends; these efforts will require adequate planning and resources to overcome the numerous barriers to intervening in this difficult to reach yet vulnerable population.
Randomized Controlled Trial of Reduced-Dose Bolus Fluorouracil Plus Leucovorin and Irinotecan or Infused Fluorouracil Plus Leucovorin and Oxaliplatin in Patients With Previously Untreated Metastatic Colorectal Cancer: A North American Intergroup Trial
Authors: Goldberg Richard M. , Sargent Daniel J. , Morton Roscoe F. , Fuchs Charles S. , Ramanathan Ramesh K. , Williamson Stephen K. , Findlay Brian P. , Pitot Henry C. , Alberts Steven
Published: July 2006

Purpose

Previously, we reported results of Intergroup N9741, which compared standard bolus fluorouracil (FU), leucovorin, plus irinotecan (IFL) with infused FU, leucovorin, plus oxaliplatin (FOLFOX4) and irinotecan plus oxaliplatin in patients with untreated metastatic colorectal cancer. High rates of grade ≥ 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4.

Patients and Methods

The primary comparison was time to progression, with secondary end points of response rate (RR), overall survival, and toxicity.

Results

Three hundred five patients were randomly assigned. The North Central Cancer Treatment Group Data Safety Monitoring Committee interrupted enrollment at a planned interim analysis when outcomes crossed predetermined stopping boundaries. The results were significantly superior for FOLFOX4 compared with rIFL for time to progression (9.7 v 5.5 months, respectively; P < .0001), RR (48% v 32%, respectively; P = .006), and overall survival (19.0 v 16.3 months, respectively; P = .026). Toxicity profiles were not significantly different between regimens for nausea, vomiting, diarrhea, febrile neutropenia, dehydration, or 60-day all-cause mortality. Sensory neuropathy and neutropenia were significantly more common with FOLFOX4. Approximately 75% of patients in both arms received second-line therapy; 58% of rIFL patients received oxaliplatin-based second-line therapy, and 55% of FOLFOX4 patients received irinotecan-based regimens as second-line therapy.

Conclusion

FOLFOX4 led to superior RR, time to progression, and overall survival compared with rIFL. The survival benefit for FOLFOX4 observed in the earlier stage of the study was preserved with equal use of either irinotecan or oxaliplatin as second-line therapy.