bluuebunny/crossref_metadata_2025 huggingface dataset:
Older Adults, Chronic Disease and Leisure-Time Physical Activity
Authors: Ashe Maureen C. , Miller William C. , Eng Janice J. , Noreau Luc
Published: June 2008

Background: Participating in regular physical activity is an important part of healthy aging. There is an increased risk for inactivity associated with aging and the risk becomes greater for adults who have a chronic disease. However, there is limited information on current physical activity levels for older adults and even less for those with chronic diseases. Objective: Our primary objective was to determine the proportion of older adults who achieved a recommended amount of weekly physical activity (≥1,000 kcal/week). The secondary objectives were to identify variables associated with meeting guideline leisure-time physical activity (LTPA), and to describe the type of physical activities that respondents reported across different chronic diseases. Methods: In this study we used the Canadian Community Health Survey Cycle 1.1 (2000/2001) to report LTPA for adults aged 65 years and older. This was a population-based self-report telephone survey. We used univariate logistic regression to provide odds ratios to determine differences in activity and the likelihood of meeting guideline recommendations. Results: For adults over 65 years of age with no chronic diseases, 30% reported meeting guideline LTPA, while only 23% met the recommendations if they had one or more chronic diseases. Factors associated with achieving the guideline amount of physical activity included a higher level of education, higherincome and moderate alcohol consumption. Likelihood for not achieving the recommended level of LTPA included low BMI, pain and the presence of mobility and dexterity problems. Walking, gardening and home exercises were the three most frequent types of reported physical activities. Conclusion: This study provides the most recent evidence to suggest that older Canadians are not active enough and this is accentuated if a chronic disease is present. It is important to develop community-based programs to facilitate LTPA, in particular for older people with a chronic disease.
The Challenges of Community-Based Research
Authors: Kleindorfer Dawn , Miller Rosie , Sailor-Smith Sharion , Moomaw Charles J. , Khoury Jane , Frankel Michael
Published: June 2008

Background and Purpose—

Public knowledge of stroke warning signs and risk factors is poor, especially in higher risk groups such as blacks. We sought to design a creative new way to educate black women by working through local beauty salons and measuring the results of the intervention.

Methods—

Thirty black beauticians were educated about stroke warning signs and risk factors in 2 large urban areas in the US. The beauticians then educated their clientele during appointments. Stroke knowledge gained was measured via de-identified pre- and post-intervention (at 6 weeks and 5 months) surveys that included open-ended questions. Stroke warning signs were taught using the “FAST” (Face, Arm, Speech, Time) method.

Results—

There were 383 completed baseline surveys, and 318 surveys were completed at 5 months. Of the 383 women, 78% were <60 years old, 69% had some college education, 41% had hypertension, and 12% had diabetes. The percentage of women who knew 3 warning signs significantly improved from the baseline survey (40.7%) to the final survey (50.6%), and similar improvements in knowledge were seen in both study regions. There was no improvement in knowledge of 3 risk factors (16.5% versus 18.2%). After our educational intervention, 94% knew to call 911 for stroke symptoms, an 8% improvement over baseline (
P
=0.002).

Conclusions—

Despite the challenges of community-based research encountered within our project, we found that stroke education in the beauty shop significantly improved knowledge regarding stroke warning signs and calling 911 among a group of black women. This improvement in knowledge was sustained for at least 5 months. Knowledge of stroke risk factors, however, did not improve. The use of the beauty shop as an educational site is a novel approach to stroke education for women that can be practically applied in the community. Education regarding stroke risk factors remains a challenge that warrants further study.
“Justice of the Marketplace”: Legal Disputes and Economic Activity on America's Northeastern Frontier, 1700–1860
Authors: Khan B. Zorina
Published: June 2008

The analysis of markets, courts, and civil litigation on the northeastern frontier of the United States provides a valuable opportunity to assess the evolution of institutions during economic development. The data set pools longitudinal and cross-sectional observations on 30,000 lawsuits filed in Maine during the critical period between 1700 and 1860. The earliest legal institutions moderated both social and economic norms, but courts quickly began to specialize in commercial issues. The residence of debtors and creditors and changes in spatial characteristics over time yield insights into the nature and extent of capital markets and impersonal exchange. The distribution and disposition of property and debt cases indicate that early markets were well developed and orderly; the evidence of “social tension” between debtors and creditors was minimal. The results do not support the standard claim of a transition from interactions based on community norms to impersonal market exchange late in the eighteenth century.
Evaluation of Precipitation Products for Global Hydrological Prediction
Authors: Voisin Nathalie , Wood Andrew W. , Lettenmaier Dennis P.
Published: June 2008

Accurate precipitation data are critical for hydrologic prediction, yet outside the developed world in situ networks are so sparse as to make alternative methods of precipitation estimation essential. Several such alternative precipitation products that would be adequate to drive hydrologic prediction models at regional and global scales are evaluated. As a benchmark, a gridded station-based dataset is used, which is compared with the global 40-yr ECMWF Re-Analysis (ERA-40), and a satellite-based dataset [i.e., the Global Precipitation Climatology Project One-Degree Daily (GPCP 1DD)]. Each dataset, with a common set of other meteorological forcings aside from precipitation, was used to force the Variable Infiltration Capacity (VIC) macroscale hydrology model globally for the 1997–99 period for which the three datasets overlapped. The three precipitation datasets and simulated hydrological variables (i.e., soil moisture, runoff, evapotranspiration, and snow water equivalent) are compared in terms of the implied water balances of the continents, and for prediction of streamflow for nine large river basins. The evaluations are in general agreement with previous but more local evaluations of precipitation products and water balances: the precipitation datasets agree reasonably on the seasonality but less on monthly anomalies. Furthermore, the largest differences in precipitation are in mountainous regions and regions where in situ networks are sparse (such as Africa). Derived runoff is highly sensitive to differences in precipitation forcings. At a global level, all three simulations result in water budgets that are within the range of other water balance climatologies. Although uncertainties in the three datasets preclude an evaluation of which one has the lowest errors, overall ERA-40 is preferred because of its agreement with the station-based dataset in locations where the station density is high, its periodic availability, and its temporal resolution.
Soil Temperature and Moisture Errors in Operational Eta Model Analyses
Authors: Godfrey Christopher M. , Stensrud David J.
Published: June 2008

Proper partitioning of the surface heat fluxes that drive the evolution of the planetary boundary layer in numerical weather prediction models requires an accurate specification of the initial state of the land surface. The National Centers for Environmental Prediction (NCEP) operational Eta Model is used to produce land surface analyses by continuously cycling soil temperature and moisture fields. These fields previously evolved only in response to radiation budget constraints and modeled precipitation, but NCEP recently upgraded the self-cycling process so that soil fields respond instead to the radiation budget and observed precipitation. A comparison of 0000 and 1200 UTC Eta Model analyses of soil temperature and moisture at several soil depths with observations from the Oklahoma Mesonet during 2004 and 2005 shows that there are strong biases in soil temperature and a severe underestimation of soil moisture at all depths. After the change to a new assimilation scheme, there is notable improvement in the magnitude of the analyzed soil moisture fields, although a strong dry bias persists in the soil moisture field. A simple one-layer slab soil model quantifies the effect of such soil moisture errors on the diurnal cycle of soil temperature and reveals that these soil moisture errors alone may account for only 1.6°C increases in predicted maximum soil temperatures during the day and temperature reductions of the same magnitude at night. The much larger remaining soil temperature errors possibly stem from documented problems with the solar radiation and longwave parameterizations within the Eta Model.
The Influence of Inversions on Rotors
Authors: Hertenstein Rolf F.
Published: June 2008

Rotors are small-scale circulations about a horizontal or quasi-horizontal axis that usually form in conjunction with high-amplitude mountain waves. The moderate to severe turbulence often found within rotors is a hazard to aviation. Observations and numerical model studies have revealed two types of mountain-wave–rotor systems. The first type is associated with trapped waves, whereas the second, less common, type resembles a hydraulic jump. It has long been known that an upstream, near-mountaintop inversion plays an important role in mountain-wave/rotor formation. In this study, the role of the upstream inversion strength and height in an environment with sheared flow and over a barrier with a steep lee slope is investigated. It is found that the second mountain-wave/rotor type is more likely to form when a strong near-mountaintop inversion is present. Baroclinic generation of horizontal vorticity within the inversion along the lee slope leads to overturning in an upstream direction and spreading of inversion isentropes. The sign and magnitude of vertical shear within the upstream inversion has a modifying influence, with positive shear favoring the formation of trapped-wave systems. Stronger inversions lead to higher-reaching, more turbulent mountain-wave/rotor systems, regardless of type.
Descending Reflectivity Cores in Supercell Thunderstorms Observed by Mobile Radars and in a High-Resolution Numerical Simulation
Authors: Byko Zack , Markowski Paul , Richardson Yvette , Wurman Josh , Adlerman Edwin
Published: June 2008

This paper is motivated by the recent interest in the “descending reflectivity cores” (DRCs) that have been observed in some supercell thunderstorms prior to the development or intensification of low-level rotation. The DRCs of interest descend on the right rear flank of the storms and are small in scale, relative to the main radar echo. They are observed to descend from the echo overhang and, upon reaching low levels, have been found to contribute to the formation or evolution of hook echoes, which are perhaps the most familiar radar characteristic of supercells. Herein, observations of DRCs obtained by a mobile Doppler radar at close range are presented. The data afford higher-resolution views of DRCs and their accompanying radial velocity fields than typically are available from operational radars, although one drawback is that some of the larger-scale perspective is sacrificed (e.g., the origin of the DRC and its possible connection to the reflectivity near the updraft summit are within the cone of silence). It is found that it is difficult to generalize a relationship between the observations of DRCs and the subsequent evolution of the low-level wind field.

The results of a three-dimensional numerical simulation of a supercell thunderstorm also are presented. DRCs are a common development within the simulation despite the use of a simple (warm rain) microphysics parameterization. The simulation allows for an investigation of the aspects of DRCs that cannot be ascertained using single-Doppler radar observations, for example, DRC formation mechanisms, the relationship between DRCs and the three-dimensional wind field, and the thermodynamic fields that accompany DRCs. Three different mechanisms are identified by which DRCs can develop in the model, not all of which are followed by increases in low-level rotation. This finding might account for the aforementioned difficulty in generalizing associations between DRCs and changes in the low-level wind field observed by mobile radar, as well as the fact that prior studies also have produced somewhat mixed results with respect to the potential of DRC detection to aid in the operational forecasting of tornadogenesis.
Internalized Heterosexism
Authors: Szymanski Dawn M. , Kashubeck-West Susan , Meyer Jill
Published: June 2008

Counseling psychologists can expect to encounter lesbian, gay, and bisexual (LGB) individuals in their lives, as students, colleagues, friends, clients, and/or family members. Most of the LGB individuals encountered by counseling psychologists have experienced the negative consequences of internalized heterosexism/internalized homophobia (IH). Yet many counseling psychologists are not adequately prepared to deal with the negative effects of IH on LGB persons' lives. This Major Contribution provides readers with a critical base of information about the construct of IH, including the historical context from which it emerged; controversies related to IH; theoretical approaches used to conceptualize IH; unique issues for women, men, and bisexuals; and the empirical research on measurement and psychosocial correlates of IH. In addition, it provides suggestions for future research and implications for counseling LGB individuals and for the training of counseling psychologists.
You Think Bart Simpson is Real. I Know He's Only an Actor!
Authors: David Matthew
Published: June 2008

Evidence of genetic links to human behaviour are readily used by some to invalidate a `blank slate' conception of human nature, while evidence of plasticity is readily used by others to invalidate genetic essentialism. Such knocking down of `straw men' helps enforce the boundaries of insular fields even as it prevents more interesting investigation of what it means to be human. This article outlines the perspective of `reflexive epistemological diversity', a perspective that overcomes the mirror imaging insularities of both epistemological reduction and relativism (itself tending towards a form of reduction to language and interaction), as well as the naivety characteristic of simple epistemological diversity.
`False Consciousness'
Authors: Kalekin-Fishman Devorah
Published: June 2008

The assumption that there is a break between what people think they are doing and how they are living, i.e. what is `really' happening to them, is the cornerstone of a sociological explanation of alienation. This assumption has been subjected to criticism, both from the point of view of quantitative researchers who ask people directly about their alienation and philosophers who reproach critical theorists for showing disrespect for people's agency. Thus, what Marx called `ideology' and Lukács `false consciousness' is discredited, and with them the concept of alienation. The article sketches discussions of the mind—body dichotomy; then presents sociological approaches to mind and body. In conclusion, it shows that an approach based on an assumption of mind—body dualism establishes the viability of the concept of `false consciousness' and thus clarifies the social structural validity of the concept of alienation.
Visual Masking Performance of a Fabric
Authors: Chen Mei-yu , Sun Run-jun , Dong Xu-ye , Lai Kan
Published: June 2008

In this study, we investigated the main factors affecting the visual masking performance of a fabric, including the illumination level of the target, the cover factor of the fabric, the distance between the fabric and the target, and the illumination level of the fabric. It was found that among these four factors, the illumination level of the target had a significant effect on the visual masking performance. The masking performance of the fabric could be improved by decreasing the illumination level of the target and by increasing the illumination level of the fabric itself. For a nylon monofilament plain fabric, the masking performance of the fabric could be improved by increasing the cover factor of the fabric. In addition, the masking performance of a fabric could be improved slightly by increasing the distance between the fabric and the target.
The Predictive Validity of the Level of Service Inventory—Revised for Drug-Involved Offenders
Authors: Kelly Christopher E. , Welsh Wayne N.
Published: June 2008

The Level of Service Inventory—Revised (LSI-R) has been validated for a variety of criminal justice populations, although one large segment for which the instrument has not been validated is drug-involved offenders. With the increasing implementation of the LSI-R across correctional jurisdictions in the United States and internationally, and with a significant number of offenders having substance abuse histories, validation of the instrument for this population is overdue. Using bivariate correlations and logistic regression analyses, the LSI-R total score was found to be a stable, significant predictor of reincarceration for a sample of 276 drug-involved offenders. This finding held up in multivariate analyses even when controlling for a variety of other factors including age, criminal history, time-at-risk in the community following release from prison, and treatment-related variables.
Nonshared Environmental Influences On Sibling Differences in Externalizing Problem Behavior
Authors: Boisvert Danielle , Wright John Paul
Published: June 2008

Using a difference scores approach, this study examines the effects of sibling differences in experiences both within and outside the home on differences in externalizing problem behavior. The results suggest that differences in parental monitoring, sibling interaction, and delinquent peer association are significantly related to sibling differences in externalizing behavior. These effects, however, appear to differ based on the sex composition of the sibling pair. Differential sibling interaction was most consistently related to differences in externalizing behavior. Differential peer association and differential parental monitoring were only significantly related to sibling differences in externalizing behavior for sister pairs and mixed-sex pairs, respectively. The importance of considering nonshared environmental influences in explaining sibling differences in behavior is discussed.
Latent Profile Analyses of Offense and Personality Characteristics in a Sample of Incarcerated Female Sexual Offenders
Authors: Turner Kim , Miller Holly A. , Henderson Craig E.
Published: June 2008

This study examines characteristics of 90 female sexual offenders based on offense and personality traits. The study uses latent profile analysis to identify groups of female sex offenders who are similar to one another and different from participants in other groups. Results using the Personality Assessment Inventory (PAI) indicate that there were three classes of offenders that differed with respect to the severity of their psychopathology. Upon analysis of predictors such as demographic information, offense characteristics, selected Trauma Symptom Inventory scores, Static-99 scores, abuse history, and PAI supplemental scales, several factors predicted group membership. These included marital status, sexual abuse in adulthood, and interpersonal relationship styles. Implications for assessment and treatment of female sex offenders are discussed.
A Markov Model Simulation of the Impact of Treatment Persistence in Postmenopausal Osteoporosis
Authors: Cotté François-Emery , Fautrel Bruno , De Pouvourville Gérard
Published: June 2008

Background . Osteoporosis is a common disorder of the skeleton that increases bone fragility and the risk of fracture. Bisphosphonates have become the reference treatment for postmenopausal osteoporosis because of their proven efficacy in reducing fracture rates. The effectiveness of bisphosphonates is, however, limited by poor treatment adherence and persistence with treatment. A model has been designed to simulate the impact of improving persistence rates on treatment effectiveness. Methods . The Markov model followed a cohort of patients over 10 years to estimate the total number of incident osteoporotic fractures by age for the overall population of women with diagnosed postmenopausal osteoporosis in France (mean age, 71.1 years ± 9.6; range, 50-96 years). The impact of clinical efficacy, persistence, and residual treatment effects data on predicted fracture risk was also estimated in the model. Results . Predicted numbers of incident fractures appeared consistent with published data. Compared with no treatment, the relative risk of fracture over 10 years was 0.831 for weekly bisphosphonate treatment with an assumed persistence rate of 51% after 1 year (absolute risk reduction = 11.4%). This relative risk decreased to 0.731 (absolute risk reduction= 18.1%) if hypothetical full-treatment persistence was achieved. In terms of public health, improving persistence with bisphosphonate treatment by only 20% could have the same impact as a 20.2% increase in clinical efficacy. The benefit associated with improved persistence declines as full persistence is approached. Conclusion . Improving persistence can increase treatment effectiveness. Giving greater priority to persistence interventions might have a greater impact on the health of osteoporotic women than advances in treatment efficacy.
The Effects of Status Violations on Hierarchy and Influence in Groups
Authors: Youngreen Reef , Moore Christopher D.
Published: June 2008

In an initial test of Wagner's (1988) status violation theory, we examine how status violations, or the failure to behave in accord with the expectations attached to a person's status position in a group, may reduce the person's status position. Status violations highlight the underlying normative order that forms the group's expectations regarding appropriate status-related behaviors. Status violators, or people whose behavior fails to comply with the expectations attached to their status position, indicate a rejection of the group's normative order and risk being labeled as a “moral violator” as a result of this explicit rejection. As such, moral violators lose status relative to people in the group whose behavior indicates their acceptance of the group's normative social order. We offer an initial experimental test of claims derived from status violation theory, which generates partial support. We describe implications of the theory and discuss further directions for research on status violations.
Analysis of Narrowband Active Noise and Vibration Control Systems Using Parallel Adaptive Notch Filters
Authors: Yang F. , Gupta A. , Kuo S.M.
Published: June 2008

This paper analyzes narrowband active noise and vibration control (ANVC) systems using multiple second-order adaptive filters configured in parallel form with the filtered-x least mean square algorithm. Theoretical analysis of convergence of the algorithm is based on the autocorrelation and crosscorrelation matrices of the overall parallel structure. Analysis results show that extra harmonics are induced in the residual error because of using a single error signal to update all adaptive filters with different sinusoidal reference signals. An optimized filter-adapting method which uses bandpass filters to split the error signal into multiple bandlimited error signals according to frequencies of reference signals is proposed to improve the performance of narrowband ANVC systems in steady state. Computer simulations are conducted to verify analysis results and performance of the optimized narrowband ANVC system.
An Experimental Study on Semi-active Seismic Response Control of a Large-span Building on Top of Ship Lift Towers
Authors: Tu Jian-Wei , Qu Wei-Lian , Jing Chen
Published: June 2008

A vertical ship lift under earthquake excitation may suffer from a violent whipping effect due to the sudden change of building lateral stiffness at the top of ship lift towers. This paper presents an experimental investigation to explore the validity of using a magnetorheological (MR) isolation system to prevent the whipping effect manipulated by neuro-fuzzy control algorithm. The two-story building was constructed as a ship lift model, in which the first story was much stiffer than the second story and the plates of the second story were divided into two mass pieces. MR isolation systems were used to link those two mass pieces. The dynamic characteristics of the model with rigid connection and with only seismic isolator connection were first identified. The models with those two connections and with MR isolation system connection were then tested under the scaled Three Gorge artificial ground motion and the scaled El Centro 1940 north-south ground motion. Finally, the seismic responses of the ship lift model were recalculated with the modified structural parameters through measured natural frequencies and were compared with the experimental seismic responses. The experimental results show that an MR isolation system manipulated by neuro-fuzzy control algorithm can achieve a significant reduction in seismic whipping effect on the building model. The comparison consequences indicate that the theoretical simulation results are accurately consistent with the experimental results.
Reorganization of the Adult Auditory System: Perceptual and Physiological Evidence From Monaural Fitting of Hearing Aids
Authors: Munro Kevin J.
Published: June 2008

Changes in the sensory environment modify our sensory experience and may result in experience-related or learning-induced reorganization within the central nervous system. Hearing aids change the sensory environment by stimulating a deprived auditory system; therefore, they may be capable of inducing changes within the central auditory system. Examples of studies that have shown hearing aid induced perceptual and/or physiological changes in the adult human auditory system are discussed. Evidence in the perceptual domain is provided by studies that have investigated (a) speech perception, (b) intensity discrimination, and (c) loudness perception. Evidence in the physiological domain is provided by studies that have investigated acoustic reflex thresholds and event-related potentials. Despite the controversy in the literature concerning the rate, extent, and clinical significance of the acclimatization effect, there is irrefutable evidence that the deprived auditory system of some listeners can be modified with hearing aid experience.
Arrested Heritage
Authors: Scholze Marko
Published: June 2008

The process of nominating a certain site or tradition as a world heritage by the United Nations Educational, Scientific and Cultural Organization (UNESCO) can be seen as a dialectic of the local and the global. A localized monument, building, town, landscape or cultural tradition becomes globalized through the inclusion into the list of world heritage. Thus, it acquires a new status as being of `outstanding universal value'. The aim of this global cultural policy as formulated by UNESCO is to enhance the pride of the local population in their own culture, foster efforts to its preservation as well as to enrich the whole of humanity in creating a cultural memory on a worldwide scale.
Recycling Recognition
Authors: De Jong Ferdinand
Published: June 2008

This article examines the recycling of a colonial memorial to African veterans in Dakar, Senegal. This act of appropriation by the Senegalese government radically transformed the significance of the memorial and reconfigured the city's memoryscape. Whilst the Senegalese government thus reclaimed colonial history as constitutive for the postcolony, it simultaneously underwrote a postcolonial claim for recognition. The article examines this case as indicative for a wider trend to claims for recognition for which recyclia seem to lend themselves par excellence. As objects of mimetic appropriation, colonial memorials can be seen as the objets trouvés of the postcolony.
Space matters
Authors: Montgomery Tim
Published: June 2008

Managing the space in which learning takes place is subject to ongoing debate. Spatial management and movement can impact upon the construction of meaning within education and upon the dynamic of learning. It is suggested that there are now different learning goals and expectations and consequently a need for different learning environments. We are urged to break out. Many constraints, however, result in everyday experience not being of high-tech, impressively designed formal and informal spaces. This article contributes to a navigation of the realities of learning space. It recognizes that the literature may be leaving the profession behind and that for many educators the opportunities of design are merely aspirations. Taking as its focal point the small seminar room with sparse furniture, it presents two studies to contribute ideas on how such non-ideal spaces might be managed; one looking at an alternative education space, the museum, and the second drawing on interviews with colleagues about their experiences.
Fostering approachability and classroom participation during the first day of class
Authors: Hermann Anthony D. , Foster David A.
Published: June 2008

Students and faculty often have different goals for the first day of class. While teaching advice books recommend actively engaging students in the course from the start, students often `shop' for classes and report being primarily concerned with gathering practical information. The aim of this article is to introduce a reciprocal interview activity that attempts to achieve both goals by creating a dynamic conversation in which the instructor inquires about the students' goals and expectations and, in turn, the students collectively interview the instructor about his or her goals and expectations. Preliminary findings indicate that students evaluate the activity favorably and feel more comfortable participating in class and more comfortable approaching the instructor about class-related and non-class-related issues after the activity. Additional benefits and uses for both students and instructors are discussed.
The effects of active learning on students' memories for course content
Authors: Cherney Isabelle D.
Published: June 2008

Two studies examined the free recall for course content of 314 American undergraduate students across various course levels. The purpose was to examine how students' memories and level of understanding for introductory materials would differ from those of more advanced classes. Across all class levels, the most frequently listed items were concepts introduced through active learning exercises, followed by videos and lecture materials. Depending on the course level and content, different types of class presentations yielded enhanced understanding of the material. Mean relevance scores were high for materials introduced with video clips in introductory classes, whereas mean scores were high for information introduced by lecture for upper level courses.
Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells
Authors: Peipp Matthias , Lammerts van Bueren Jeroen J. , Schneider-Merck Tanja , Bleeker Wim W. K. , Dechant Michael , Beyer Thomas , Repp Roland , van Berkel Patrick H. C. , Vink Tom , van de Winkel Jan G. J. , Parren Paul W. H. I. , Valerius Thomas
Published: June 2008

Glycosylation of the antibody Fc fragment is essential for Fc receptor–mediated activity. Carbohydrate heterogeneity is known to modulate the activity of effector cells in the blood, in which fucosylation particularly affects NK cell–mediated killing. Here, we investigated how the glycosylation profile of 2F8, a human IgG1 monoclonal antibody against epidermal growth factor receptor in clinical development, impacted effector function. Various 2F8 batches differing in fucosylation, galactosylation, and sialylation of the complex-type oligosaccharides in the Fc fragment were investigated. Our results confirmed that low fucose levels enhance mononuclear cell–mediated antibody-mediated cellular cytotoxicity (ADCC). In contrast, polymorphonuclear cells were found to preferentially kill via high-fucosylated antibody. Whole blood ADCC assays, containing both types of effector cells, revealed little differences in tumor cell killing between both batches. Significantly, however, high-fucose antibody induced superior ADCC in blood from granulocyte colony-stimulating factor–primed donors containing higher numbers of activated polymorphonuclear cells. In conclusion, our data demonstrated for the first time that lack of fucose does not generally increase the ADCC activity of therapeutic antibodies and that the impact of Fc glycosylation on ADCC is critically dependent on the recruited effector cell type.
Head to head comparison of 2D vs real time 3D dipyridamole stress echocardiography
Authors: Varnero Silvia , Santagata Patricia , Pratali Lorenza , Basso Massimiliano , Gandolfo Alfredo , Bellotti Paolo
Published: June 2008

Real-time three-dimensional (RT-3D) echocardiography has entered the clinical practice but true incremental value over standard two-dimensional echocardiography (2D) remains uncertain when applied to stress echo. The aim of the present study is to establish the additional value of RT-3D stress echo over standard 2D stress echocardiography. We evaluated 23 consecutive patients (age = 65 ± 10 years, 16 men) referred for dipyridamole stress echocardiography with Sonos 7500 (Philips Medical Systems, Palo, Alto, CA) equipped with a phased – array 1.6–2.5 MHz probe with second harmonic capability for 2D imaging and a 2–4 MHz matrix-phased array transducer producing 60 × 70 volumetric pyramidal data containing the entire left ventricle for RT-3D imaging. In all patients, images were digitally stored in 2D and 3D for baseline and peak stress with a delay between acquisitions of less than 60 seconds. Wall motion analysis was interpreted on-line for 2D and off-line for RT-3D by joint reading of two expert stress ecocardiographist. Segmental image quality was scored from 1 = excellent to 5 = uninterpretable. Interpretable images were obtained in all patients. Acquisition time for 2D images was 67 ± 21 sec vs 40 ± 22 sec for RT-3D (p = 0.5). Wall motion analysis time was 2.8 ± 0.5 min for 2D and 13 ± 7 min for 3D (p = 0.0001). Segmental image quality score was 1.4 ± 0.5 for 2D and 2.6 ± 0.7 for 3D (p = 0.0001). Positive test results was found in 5/23 patients. 2D and RT-3D were in agreement in 3 out of these 5 positive exams. Overall stress result (positive vs negative) concordance was 91% (Kappa = 0.80) between 2D and RT-3D. During dipyridamole stress echocardiography RT-3D imaging is highly feasible and shows a high concordance rate with standard 2D stress echo. 2D images take longer time to acquire and RT-3D is more time-consuming to analyze. At present, there is no clear clinical advantage justifying routine RT-3D stress echocardiography use.
Investigating the complexity of respiratory patterns during the laryngeal chemoreflex
Authors: Dragomir Andrei , Akay Yasemin , Curran Aidan K , Akay Metin
Published: June 2008

Background

The laryngeal chemoreflex exists in infants as a primary sensory mechanism for defending the airway from the aspiration of liquids. Previous studies have hypothesized that prolonged apnea associated with this reflex may be life threatening and might be a cause of sudden infant death syndrome.

Methods

In this study we quantified the output of the respiratory neural network, the diaphragm EMG signal, during the laryngeal chemoreflex and eupnea in early postnatal (3–10 days) piglets. We tested the hypothesis that diaphragm EMG activity corresponding to reflex-related events involved in clearance (restorative) mechanisms such as cough and swallow exhibit lower complexity, suggesting that a synchronized homogeneous group of neurons in the central respiratory network are active during these events. Nonlinear dynamic analysis was performed using the approximate entropy to asses the complexity of respiratory patterns.

Results

Diaphragm EMG, genioglossal activity EMG, as well as other physiological signals (tracheal pressure, blood pressure and respiratory volume) were recorded from 5 unanesthetized chronically instrumented intact piglets. Approximate entropy values of the EMG during cough and swallow were found significantly (p < 0.05 and p < 0.01 respectively) lower than those of eupneic EMG.

Conclusion

Reduced complexity values of the respiratory neural network output corresponding to coughs and swallows suggest synchronous neural activity of a homogeneous group of neurons. The higher complexity values exhibited by eupneic respiratory activity are the result of a more random behaviour, which is the outcome of the integrated action of several groups of neurons involved in the respiratory neural network.
Anti‐ganglioside Antibodies and the Presynaptic Motor Nerve Terminal
Authors: Willison Hugh J. , Plomp Jaap J.
Published: June 2008

The Guillain Barré syndromes (GBS) are the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the pathophysiological events of GBS, and improving immunotherapies are fundamental to improving the clinical outcome. Recent research into GBS and the Miller Fisher syndrome (MFS) variant has focused on the forms mediated by anti‐ganglioside antibodies in which correlations have been established between anti‐ganglioside antibodies and specific clinical phenotypes, notably between anti‐GM1/GD1a antibodies and the acute motor axonal variant and anti‐GQ1b/GT1a antibodies and MFS. Anti‐ganglioside antibodies can arise through molecular mimicry with GBS‐associated Campylobacter jejuni oligosaccharides. Our work has focused on axonal and glial components of the motor nerve terminal as a model site of injury, and through combined active and passive immunization paradigms in glycosyltransferase knockout mice we have developed murine neuropathy phenotypes mediated by anti‐ganglioside antibodies. Several determinants influence disease expression including the level of immunological tolerance to microbial glycans that mimic self gangliosides, the degree of complement activation, and the ganglioside density in target tissue. Such studies provide us with clear information on an antibody‐mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in man.
Status of the Thymectomy Trial for Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone
Authors: Newsom‐Davis John , Cutter Gary , Wolfe Gil I. , Kaminski Henry J. , Jaretzki III Alfred , Minisman Greg , Aban Inmaculada , Conwit Robin
Published: June 2008

The primary study [MGTX] aims to answer three questions: does extended transsternal thymectomy combined with the prednisone protocol, when compared with the prednisone protocol alone: (1) result in a greater improvement in myasthenic weakness, (2) result in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long‐term toxic effects, (3) enhance the quality of life by reducing adverse events and symptoms associated with the therapies? Inclusion criteria are MGFA Class 2, 3, or 4; acetylcholine receptor antibody positive; age at least 18.0 years and <60.0 years; MG history of <3 years. Patients can be prednisone naïve or not. The National Institute for Neurological Disorders and Stroke awarded funding for MGTX in September 2005, and NIH awarded funding for the ancillary Biomarkers study (BioMG) in February 2006. Diverse regulatory obstacles have been encountered in this international study, but we now have a total of over 70 centers in 22 countries (North America, South America, Europe, Australasia, South Africa) either actively recruiting or at various levels of readiness.
Antigen‐specific Apheresis of Pathogenic Autoantibodies from Myasthenia Gravis Sera
Authors: Tzartos Socrates J. , Bitzopoulou Kalliopi , Gavra Ira , Kordas Grigoris , Jacobson Leslie , Kostelidou Kalliopi , Lagoumintzis George , Lazos Orestis , Poulas Kostantinos , Sideris Sotiris , Sotiriadis Alexandros , Trakas Nikos , Zisimopoulou Paraskevi
Published: June 2008

Myasthenia gravis (MG) is usually caused by autoantibodies against muscle nicotinic acetylcholine receptor (AChR), which is composed of five subunits (α2βγδ or α2βɛδ). Current treatments, including plasmapheresis, are nonspecific, causing several side effects. We aim to develop an antigen‐specific alternative to plasmapheresis, since the latter removes indispensable plasma components in addition to anti‐AChR antibodies. We are developing a method for the selective depletion of the anti‐AChR autoantibodies from patients' plasma through the construction of “immunoadsorbent” columns carrying AChR domains. We have expressed the extracellular domains (ECDs, amino acids ∼1–210/220) of all human muscle AChR subunits in Pichia pastoris and, in preliminary experiments, in E. coli. The ECDs were immobilized (individually or mixed) on Sepharose beads, producing Sepharose‐ECD columns, which were tested for their immunoadsorbing capacity on MG sera and shown to specifically eliminate major autoantibody fractions from several MG sera. The immobilized ECDs remained stable and did not dissociate from their matrix after incubation with serum, whereas the procedure was neither toxic nor immunogenic in two experimental rabbits. Testing the intact or antibody‐depleted MG sera and the affinity purified autoantibodies showed that both the intact sera and the purified autoantibodies, but not the antibody‐depleted sera, could induce AChR loss in cell cultures and experimental MG in rats. This preliminary study suggests that the myasthenic potency of MG sera is entirely due to their anti‐AChR antibodies and therefore their depletion should be of therapeutic value. We conclude that ECD‐mediated immunoadsorption can be used as an efficient, antigen‐specific therapy for MG.
Cell‐to‐Cell Signaling at the Neuromuscular Junction
Authors: Werle Michael J.
Published: June 2008

The extracellular matrix at the neuromuscular junction plays many roles. The matrix plays a structural role in that it maintains the spatial relationship between the muscle cell, Schwann cell, and presynaptic motor neuron. The matrix also plays a role in cell‐to‐cell signaling. The most studied member of this group is the heparan sulfate proteoglycan, agrin. Agrin is an integral member of the synaptic matrix, and it plays the pivotal role of instructing the muscle cell to aggregate acetylcholine receptors (AChRs) to the synapse. Agrin is released by the motor neuron, where it binds stably to the extracellular matrix. Agrin interacts with the muscle‐specific tyrosine kinase (MuSK). Mice that lack agrin, or MuSK, fail to form neuromuscular junctions. Thus, the extracellular matrix is critical to both the structure and function of the neuromuscular junction.

Remodeling of the extracellular matrix at the neuromuscular junction is needed to maintain stability, to allow growth, or to destabilize and remove synapses. Matrix metalloproteinases are key regulators of the extracellular matrix. In particular, matrix metalloproteinase 3 (MMP3) has been implicated in regulation of synaptic structure. MMP3 cleaves agrin. Antibodies to MMP3 recognize molecules concentrated at the synapses of frog neuromuscular junctions. Neuromuscular junctions in MMP3 null mutant mice have increased junctional folds, and AChR aggregates. Changes in synaptic activity will alter the activity of MMP3 at the synapse. Thus, the extracellular matrix is critical to the formation of the synapse, and synaptic activity controls the structure and function of the molecules in the extracellular matrix.
Congenital Myasthenic Syndromes and the Formation of the Neuromuscular Junction
Authors: Beeson David , Webster Richard , Cossins Judith , Lashley Daniel , Spearman Hayley , Maxwell Susan , Slater Clarke R. , Newsom‐Davis John , Palace Jacqueline , Vincent Angela
Published: June 2008

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders affecting neuromuscular transmission. Underlying mutations have been identified in at least 11 different genes. The majority of CMS patients have disorders due to mutations in postsynaptic proteins. Initial studies focused on dysfunction of the acetylcholine receptor (AChR) itself as the major cause of CMS. However, it is becoming apparent that mutations of proteins involved in clustering the AChR and maintaining neuromuscular junction structure form important subgroups. Analysis of the mutations in the AChR‐clustering protein, rapsyn, show diverse causes for defective AChR localization and suggest that the common mutation rapsyn‐N88K results in AChR clusters that are less stable than those generated by wild‐type rapsyn. More recently, mutations in the newly identified endplate protein Dok‐7 have been shown to affect AChR clustering and the generation and maintenance of specialized structures at the endplate. Dok‐7 binds MuSK and many of the mutations of DOK7 impair the MuSK signaling pathway. Components of this pathway will provide attractive gene candidates for additional forms of CMS. The phenotypic characteristics of the different CMS in which muscle groups may be differentially affected not only provide clues for targeted genetic screening, but also pose further intriguing questions about underlying molecular mechanisms.
Regulation of Insulin-Response Element Binding Protein-1 in Obesity and Diabetes: Potential Role in Impaired Insulin-Induced Gene Transcription
Authors: Chahal Jaspreet , Chen Ching-Chu , Rane Madhavi J. , Moore Joseph P. , Barati Michelle T. , Song Ying , Villafuerte Betty C.
Published: June 2008

One of the major mechanisms by which insulin modulates glucose homeostasis is through regulation of gene expression. Therefore, reduced expression of transcription factors that are required for insulin-regulated gene expression may contribute to insulin resistance. We recently identified insulin response element-binding protein-1 (IRE-BP1) as a transcription factor that binds and transactivates multiple insulin-responsive genes, but the regulation of IRE-BP1 in vivo is largely unknown. In this study, we show that IRE-BP1 interacts with the insulin response sequence of the IGF-I, IGFBP-1, and IGFBP-3 genes using chromatin immunoprecipitation assay. Furthermore, activation by IRE-BP1 is sequence specific and mimics that of the insulin effect on gene transcription. Tissue expression of IRE-BP1 is 50- to 200-fold higher in classical insulin target compared with nontarget tissues in lean animals, with a significantly reduced level of expression in the skeletal muscle and adipose tissue in obese and diabetic animals. In the liver, IRE-BP1 is localized to the nucleus in lean rats but is sequestered to the cytoplasm in obese and diabetic animals. Cytoplasmic sequestration appears to be related to inhibition of insulin-mediated phosphatidylinositol-3 kinase signaling. Therefore, in diabetes and obesity, the mechanisms involved in reducing the transactivation of the insulin response sequence by IRE-BP1 include decreased gene transcription and nuclear exclusion to prevent DNA binding. Our study supports the notion that IRE-BP1 may be relevant to the action of insulin in vivo and may play a role in the development of insulin resistance and diabetes.