bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Variation in the β2 Subunit of the Voltage-Gated Calcium Channel and Pharmacogenetic Association With Adverse Cardiovascular Outcomes in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES)
Authors: Niu Yuxin , Gong Yan , Langaee Taimour Y. , Davis Heather M. , Elewa Hazem , Beitelshees Amber L. , Moss James I. , Cooper-DeHoff Rhonda M. , Pepine Carl J. , Johnson Julie A.
Published: December 2010

Background—

Single-nucleotide polymorphisms (SNPs) within the regulatory β2 subunit of the voltage-gated calcium channel (
CACNB2
) may contribute to variable treatment response to antihypertensive drugs and adverse cardiovascular outcomes.

Methods and Results—

SNPs in
CACNB2
from 60 ethnically diverse individuals were identified and characterized. Three common SNPs (rs2357928, rs7069292, and rs61839258) and a genome-wide association study-identified intronic SNP (rs11014166) were genotyped for a clinical association study in 5598 hypertensive patients with coronary artery disease randomized to a β-blocker (BB) or a calcium channel blocker (CCB) treatment strategy in the INternational VErapamil SR-Trandolapril STudy GENEtic Substudy (INVEST-GENES). Reporter gene assays were conducted on the promoter SNP, showing association with clinical outcomes. Twenty-one novel SNPs were identified. A promoter A>G SNP (rs2357928) was found to have significant interaction with treatment strategy for adverse cardiovascular outcomes (
P
for interaction, 0.002). In whites, rs2357928 GG patients randomized to CCB were more likely to experience an adverse outcome than those randomized to BB treatment strategy, with adjusted hazard ratio (HR) (CCB versus BB) of 2.35 (95% CI, 1.19 to 4.66;
P
=0.014). There was no evidence for such treatment difference in AG (HR, 1.16; 95% CI, 0.75 to 1.79;
P
=0.69) and AA (HR, 0.63; 95% CI, 0.36 to 1.11;
P
=0.11) patients. This finding was consistent in Hispanics and blacks.
CACNB2
rs11014166 showed similar pharmacogenetic effect in Hispanics, but not in whites or blacks. Reporter assay analysis of rs2357928 showed a significant increase in promoter activity for the G allele compared to the A allele.

Conclusions—

These data suggest that genetic variation within
CACNB2
may influence treatment-related outcomes in high-risk patients with hypertension.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00133692.
Heterogeneity of the Phenotypic Definition of Coronary Artery Disease and Its Impact on Genetic Association Studies
Authors: Kitsios Georgios D. , Dahabreh Issa J. , Trikalinos Thomas A. , Schmid Christopher H. , Huggins Gordon S. , Kent David M.
Published: December 2010

Background—

Variability in phenotypic characterization of coronary artery disease (CAD) may contribute to the heterogeneity of genetic association studies, and more consistency in phenotype definitions might improve replication of genetic associations. We assessed the extent of phenotypic heterogeneity and quantified its impact in a large literature sample of association studies.

Methods and Results—

We searched for large (≥15 studies) meta-analyses of genetic associations and reviewed all studies included therein. From each primary study, we extracted phenotypic definitions, demographics, study design characteristics, and genotypic data. For each association, we assessed the magnitude and heterogeneity of genetic effects within and across CAD phenotypes, using meta-analytic methodologies. A total of 965 individual studies investigating 32 distinct variants in 22 genes were included, from which we grouped CAD phenotypes into 3 categories: acute coronary syndromes (ACS) (426 [44%] studies); angiographically documented disease (323 [34%] studies); and broad, not otherwise specified CAD (216 [22%] studies). These clinical phenotypes were overlapping. Subgroup meta-analyses by phenotype showed discordant results, but phenotypic classification generally explained small proportions of between-study heterogeneity. Differences between phenotypic groups were minimized for associations with robust statistical support. No CAD phenotype was consistently associated with larger or more homogeneous genetic effects in meta-analyses.

Conclusions—

Substantial phenotypic heterogeneity exists in CAD genetic associations, but differences in phenotype definition make a small contribution to between-study heterogeneity. We did not find a consistent effect in terms of the magnitude or homogeneity of summary effects for a specific phenotype to support its preferential use in genetic studies or meta-analyses for CAD.
Balanced Contribution to the Intensification of a Tropical Cyclone Simulated in TCM4: Outer-Core Spinup Process*
Authors: Fudeyasu Hironori , Wang Yuqing
Published: December 2010

The balanced contribution to the intensification of a tropical cyclone simulated in the three-dimensional, nonhydrostatic, full-physics tropical cyclone model version 4 (TCM4), in particular the spinup of the outer-core circulation, is investigated by solving the Sawyer–Eliassen equation and by computing terms in the azimuthal-mean tangential wind tendency equation. Results demonstrate that the azimuthal-mean secondary circulation (radial and vertical circulation) and the spinup of the midtropospheric outer-core circulation in the simulated tropical cyclone are well captured by balance dynamics. The midtropospheric inflow develops in response to diabatic heating in mid–upper-tropospheric stratiform (anvil) clouds outside the eyewall in active spiral rainbands and transports absolute angular momentum inward to spin up the outer-core circulation. Although the azimuthal-mean diabatic heating rate in the eyewall is the largest, its contribution to radial winds and thus the spinup of outer-core circulation in the middle troposphere is rather weak. This is because the high inertial stability in the inner-core region resists the radial inflow in the middle troposphere, limiting the inward transport of absolute angular momentum. The result thus suggests that diabatic heating in spiral rainbands is the key to the continued growth of the storm-scale circulation.
Comparison of Two-Moment Bulk Microphysics Schemes in Idealized Supercell Thunderstorm Simulations
Authors: Morrison Hugh , Milbrandt Jason
Published: December 2010

Idealized three-dimensional supercell simulations were performed using the two-moment bulk microphysics schemes of Morrison and Milbrandt–Yau in the Weather Research and Forecasting (WRF) model. Despite general similarities in these schemes, the simulations were found to produce distinct differences in storm structure, precipitation, and cold pool strength. In particular, the Morrison scheme produced much higher surface precipitation rates and a stronger cold pool, especially in the early stages of storm development. A series of sensitivity experiments was conducted to identify the primary differences between the two schemes that resulted in the large discrepancies in the simulations.

Different approaches in treating graupel and hail were found to be responsible for many of the key differences between the baseline simulations. The inclusion of hail in the baseline simulation using the Milbrant–Yau scheme with two rimed-ice categories (graupel and hail) had little impact, and therefore resulted in a much different storm than the baseline run with the single-category (hail) Morrison scheme. With graupel as the choice of the single rimed-ice category, the simulated storms had considerably more frozen condensate in the anvil region, a weaker cold pool, and reduced surface precipitation compared to the runs with only hail, whose higher terminal fall velocity inhibited lofting. The cold pool strength was also found to be sensitive to the parameterization of raindrop breakup, particularly for the Morrison scheme, because of the effects on the drop size distributions and the corresponding evaporative cooling rates. The use of a more aggressive implicit treatment of drop breakup in the baseline Morrison scheme, by limiting the mean–mass raindrop diameter to a maximum of 0.9 mm, opposed the tendency of this scheme to otherwise produce large mean drop sizes and a weaker cold pool compared to the hail-only run using the Milbrandt–Yau scheme.
3D-Var Assimilation of Insect-Derived Doppler Radar Radial Winds in Convective Cases Using a High-Resolution Model
Authors: Rennie S. J. , Dance S. L. , Illingworth A. J. , Ballard S. P. , Simonin D.
Published: December 2010

The assimilation of Doppler radar radial winds for high-resolution NWP may improve short-term forecasts of convective weather. Using insects as the radar target, it is possible to provide wind observations during convective development. This study aims to explore the potential of these new observations, with three case studies. Radial winds from insects detected by four operational weather radars were assimilated using three-dimensional variational data assimilation (3D-Var) into a 1.5-km resolution version of the Met Office Unified Model, using a southern U.K. domain and no convective parameterization. The effect on the analyzed wind was small, with changes in direction and speed up to 45° and 2 m s−1, respectively. The forecast precipitation was perturbed in space and time but not substantially modified. Radial wind observations from insects show the potential to provide small corrections to the location and timing of showers, but not to completely relocate convergence lines. Overall, quantitative analysis indicated the observation impact in the three case studies was small and neutral. However, the small sample size and possible ground clutter contamination issues preclude unequivocal impact estimation. The study shows the potential positive impact of insect winds; future operational systems using dual-polarization radars that are better able to discriminate between insects and clutter returns should provide a much greater impact on forecasts.
What is the Goal? Framing the Climate Change Adaptation Question through a Problem-Oriented Approach
Authors: Roman Carolina E. , Lynch Amanda H. , Dominey-Howes Dale
Published: December 2010

A problem-oriented and interdisciplinary approach was employed at Alpine Shire, in northeast Victoria, Australia, to explore its tourism sector’s contextual vulnerability and adaptability to stressors that include but are not limited to climatic change. Using a policy sciences approach, the objective was to identify factors that influence existing vulnerabilities and that might consequently act as barriers to effective adaptation. To do this, a particular focus was placed on identifying the underlying values embedded in social and decision processes and their role in shaping preferred adaptation outcomes. Analyses of social processes suggest that many threats, including the effects climate change, compete for the resources, strategy, and direction of local tourism management bodies. Many complex and interacting factors define the vulnerability and adaptive capacity of the shire’s tourism sector to the challenges of global change, including local socioeconomic issues as well as exposure to external factors of macroscale. These issues represent more immediate concerns than future climate change scenarios, revealing an approximation of the common interest in working toward adaptation and sustainability.
Bioengineered Periodontal Tissue Formed on Titanium Dental Implants
Authors: Lin Y. , Gallucci G.O. , Buser D. , Bosshardt D. , Belser U.C. , Yelick P.C.
Published: December 2010

The ability to use autologous dental progenitor cells (DPCs) to form organized periodontal tissues on titanium implants would be a significant improvement over current implant therapies. Based on prior experimental results, we hypothesized that rat periodontal ligament (PDL)-derived DPCs can be used to bioengineer PDL tissues on titanium implants in a novel, in vivo rat maxillary molar implant model. Analyses of recovered implants revealed organized PDL tissues surrounding titanium implant surfaces in PDL-cell-seeded, and not in unseeded control, implants. Rat PDL DPCs also exhibited differentiative potential characteristic of stem cells. These proof-of-principle findings suggest that PDL DPCs can organize periodontal tissues in the jaw, at the site of previously lost teeth, indicating that this method holds potential as an alternative approach to osseointegrated dental implants. Further refinement of this approach will facilitate the development of clinically relevant methods for autologous PDL regeneration on titanium implants in humans.
Oral Epithelial Cells are Activated via TRP Channels
Authors: Wang B. , Danjo A. , Kajiya H. , Okabe K. , Kido M.A.
Published: December 2010

Transient receptor potential (TRP) ion channels are critical contributors to the perception of various environmental stimuli. Although the oral cavity is the access point for various food types, the expression of TRP channels in oral mucosa remains unknown. We hypothesized that the oral epithelium itself may participate in sensing thermal, mechanical, and chemical conditions. The expression profiles of TRP channels exhibited regional differences among the buccal, palatal, and tongue epithelia. Changes in elevated intracellular Ca2+ concentration ([Ca2+]i) in oral epithelial cells were found after stimulation of the TRP channels with capsaicin, camphor, 4α-phorbol-12,13 didecanoate (4α-PDD), 2-aminoethoxydiphenyl borate (2-APB), and menthol. These increases in Ca2+ appeared dependent on the TRP channels, because [Ca2+]i suppression was observed after the addition of the TRPV channel antagonist ruthenium red. These results demonstrate that the oral epithelia express various TRP channels and may have functional roles in sensory activities, together with neurons.
Reconstructing arrival processes to discrete queueing systems by inverse load transformation
Authors: Heckmüller Stephan , Wolfinger Bernd E.
Published: December 2010

In this article we propose methods to estimate the parameters of arrival processes to G/ D/1 queueing systems only based on observed departures from the system. The derived estimates can be used for performance evaluation and capacity planning in cases where the arrival process is not observable directly. Instead, only the departure process modified at the (last) server needs to be observed. Concerning the arrival process we begin by focusing on the normally distributed number of arrivals per interval and on autoregressive processes. Both classes can be used to model traffic in communication networks on links with a high degree of aggregation. In the case of autoregressive processes we apply the Tobit regression model in order to derive accurate estimates of all parameters of the arrival process. We then continue by generalizing the estimation procedures to correlated arrival processes by using the Buckley–James Estimator. The results are presented for the single G/ D/1 queue but are then generalized to the more realistic scenario of sequences of queues with possibly varying bottleneck capacity. The latter especially permits the modeling of effects due to interfering cross traffic. We show how the derived estimates can be used for performance evaluation or capacity planning based on effective bandwidth theory. Finally, we demonstrate that the estimation procedures can be utilized within wireless networks by means of a detailed simulation model.
The Enclosure of Urban Space and Consolidation of the Capitalist Land Regime in Turkish Cities
Authors: Balaban Utku
Published: December 2010

This article discusses the role of squatters in the commodification of urban space in Turkey since the 1960s. Although squatting until the early 1980s was regarded as the expression of the demands of rural-to-urban migrants for their citizenship rights, early migrants eventually built multistorey buildings on the plots they occupied and rented the extra space to late migrants. Thus, squatting as ‘self-help put into practice’ became a major mechanism of commodification of urban land in Turkey. The commodification brought about significant antagonism between early migrants/new petty bourgeois and late migrants/new working class, as the latter became the tenants of the former. This division in working-class neighbourhoods is mostly invisible to the current literature. However, if this historical transformation is conceptualised as the ‘enclosure of urban space’, contradictions among different segments of squatter communities can be analysed in a comparative manner.
Job Qualification, Distance between Towns and Geographical Relocation for French Youth
Authors: Lemistre Philippe , Magrini Marie-Benoit
Published: December 2010

Geographical mobility of professionally active youth is often considered as an attribute of the most qualified among them. Nevertheless, joint consideration of geographical relocation at an infraregional scale and of the distance travelled in migration between cities shows that the spatial mobility of youth towards the least-qualified jobs is not only non-negligible, but displays substantial amplitude. Even so, mobility behaviour still differs according to the qualification level of the targeted employment and is particularly dependent on territorial characteristics as well.
Contesting Territorial Fixity? A Case Study of Regeneration in Belfast
Authors: O’Dowd Liam , Komarova Milena
Published: December 2010

This paper looks at urban regeneration in Belfast as a stage on which the interaction between different structural dynamics (political, economic and cultural) is manifested in the city. It discusses how contested ideas of ‘space’, ‘place’ and ‘territory’ frame the ways in which Belfast has changed over recent years and asks if regeneration itself has the potential to transform the dynamic of deep-rooted ethno-national divisions. The research question is explored through a case study of proposed urban regeneration in north Belfast. It is found that, while there is evidence of transition to less exclusivistic attitudes in leisure and work spaces, asymmetrical conflict over residential space persists in ways which reproduce deep-rooted political and cultural patterns of territorial fixity and division.
Transcriptional Profiling of Liver and Effect of Glucocorticoids in a Rat Adjuvant-Induced Arthritis Model
Authors: Song Y. L. , Foster W. R. , Shuster D. J. , Nadler S. G. , Salter-Cid L. , Sasseville V. G.
Published: December 2010

Glucocorticoids (GCs), despite having many undesirable side effects, remain effective for the treatment of many inflammatory diseases and are commonly used as benchmark drugs in animal models of disease. However, the molecular mechanisms underling systemic GC effects in these models are poorly characterized. In this study, prednisolone and dexamethasone were evaluated in the fully established Lewis rat adjuvant-induced arthritis (AIA) model. In AIA, adjuvant administration induced polyarticular and systemic inflammation, which included spleen and liver. In the liver, multifocal hepatic granulomas were observed. To characterize the systemic response and the pathways responsible for GC effects, histology, transcriptional profiling, and immunohistochemistry (IHC) were performed. There was a decrease in the incidence and histologic severity score for granulomas with GC treatment. There was no effect on cellular composition of granulomas as assessed by IHC for CD3+ lymphocytes, macrophages, and B cells, but there was a significant reduction in infiltrating lymphocytes in the hepatic parenchyma. By Affymetrix microarray analysis, 10% of hepatic transcripts were altered ( P < .01) in livers from AIA rats, with ~31% of them partially reversed with treatment with dexamethasone and ~13% with prednisolone. Many of these altered hepatic transcripts correspond to human genes that are dysregulated in the synovium in human rheumatoid arthritis (RA), indicating that the rat AIA model shares features with human RA. These data establish molecular changes in the liver and the effect of GCs in rat AIA, which can be used to aid in understanding the mechanism of action of novel anti-inflammatory compounds in this animal model.
A Critical Realist Orientation to Learner Needs
Authors: Ayers David F.
Published: December 2010

The objective of this essay is to propose critical realism as a philosophical middle way between two sets of ontological, epistemological, and methodological assumptions regarding learner needs. Key concepts of critical realism, a tradition in the philosophy of science, are introduced and applied toward an analysis of learner needs, resulting in novel ontological and epistemological assertions about learner needs. Retroduction is offered as a methodology for interrogating needs as a function of broad and complex social processes.
Language Style Matching Predicts Relationship Initiation and Stability
Authors: Ireland Molly E. , Slatcher Richard B. , Eastwick Paul W. , Scissors Lauren E. , Finkel Eli J. , Pennebaker James W.
Published: December 2010

Previous relationship research has largely ignored the importance of similarity in how people talk with one another. Using natural language samples, we investigated whether similarity in dyads’ use of function words, called language style matching (LSM), predicts outcomes for romantic relationships. In Study 1, greater LSM in transcripts of 40 speed dates predicted increased likelihood of mutual romantic interest (odds ratio = 3.05). Overall, 33.3% of pairs with LSM above the median mutually desired future contact, compared with 9.1% of pairs with LSM at or below the median. In Study 2, LSM in 86 couples’ instant messages positively predicted relationship stability at a 3-month follow-up (odds ratio = 1.95). Specifically, 76.7% of couples with LSM greater than the median were still dating at the follow-up, compared with 53.5% of couples with LSM at or below the median. LSM appears to reflect implicit interpersonal processes central to romantic relationships.
Popularization by Argentine researchers: the activities and motivations of CONICET scientists
Authors: Kreimer Pablo , Levin Luciano , Jensen Pablo
Published: December 2010

This paper presents the findings of a survey on popularization activities by 1700 scientists in Argentina. The tool used for this research was a questionnaire containing 21 questions on discipline, age, status in hierarchy, intensity of popularization activity, motives, difficulties and opinions on public issues and science policy. Our analysis of the data shows that patterns of public popularization in Argentina do not substantially differ from those found in two advanced countries, namely France and the United Kingdom. This situation contrasts with the strong differences found in research practices in “central” and “peripheral” countries.
Academic staff and public communication: a survey of popular science publishing across 13 countries
Authors: Bentley Peter , Kyvik Svein
Published: December 2010

This study is a cross-national empirical analysis of popular science publishing among university staff in a 13-country sample. The countries included in the study are: Argentina, Australia, Brazil, Canada, Finland, Germany, Hong Kong, Italy, Malaysia, Mexico, Norway, the UK and the USA. The study seeks to quantify the extent of popular science publishing and its relationship with scientific publishing. Popular science publishing was measured as the number of articles written by scientists in newspapers and magazines over the three-year period 2005-07. Our findings suggest that popular science publishing is undertaken by a minority of academic staff and to a far lesser extent than scientific publishing. Despite the arguably fewer rewards associated with publishing for the non-specialist public, our data suggests that academic staff with popular publications have higher levels of scientific publishing and academic rank. The positive relationship between scientific and popular publishing is consistent across all countries and academic fields. The extent of popular science publishing varies with field and country.
Which indicators for the new public engagement activities? An exploratory study of European research institutions
Authors: Neresini Federico , Bucchi Massimiano
Published: December 2010

Public engagement (PE) activities have become a regular feature for several research institutions in Europe. However, while research and teaching functions can count on established indicators, PE functions are often performed as a sort of “goodwill exercise.” Few studies have focused on defining appropriate indicators and standards, particularly at the organizational level. An exploratory study was carried out on a sample of 40 European research institutions with a view to understanding whether the diffusion of PE activities has led to incorporating the PE perspective into “routine” activities of organizations. The results point to quite unequal performances among European research institutions. Also, while most research institutions examined have dedicated resources for PE activities, the study suggests that such activities are not yet considered essential. Performance indicators and standards might prove of great support for institutions and policy actors that wish to take seriously the challenge of public engagement and societal dialogue.
“My Greatest Dream is to be Normal”: The Impact of Gender on the Depression Narratives of Young Swedish Men and Women
Authors: Danielsson Ulla E. , Bengs Carita , Samuelsson Eva , Johansson Eva E.
Published: December 2010

Depression is common among young people. Gender differences in diagnosing depression appear during adolescence. The study aim was to explore the impact of gender on depression in young Swedish men and women. Grounded theory was used to analyze interviews with 23 young people aged 17 to 25 years who had been diagnosed with depression. Their narratives were marked by a striving to be normal and disclosed strong gender stereotypes, constructed in interaction with parents, friends, and the media. Gender norms were upheld by feelings of shame, and restricted the acting space of our informants. However, we also found transgressions of these gender norms. Primary health care workers could encourage young men to open up emotionally and communicate their personal distress, and young women to be daring and assertive of their own strengths, so that both genders might gain access to the positive coping strategies practiced respectively by each.
Issues of Expressed Stigma of HIV/AIDS Among Professionals in Southern Sudan
Authors: Machine Edwin M. , Ross Michael W. , McCurdy Sheryl A.
Published: December 2010

HIV-related stigma continues to be a significant barrier to HIV testing, treatment, and care. Understanding the factors that underlie this stigma could help remove barriers to HIV/AIDS intervention. We identified these factors among nurses as well as community leaders in Lui, Southern Sudan. Participants included health workers at a local hospital, a women’s group, local market traders, religious leaders, and teachers. We categorized the responses generated from group interaction forums as concerns, fears, and perceptions. We found that stigma persisted not only toward people with conspicuous signs of full-blown AIDS, but also toward community programs, like voluntary counseling and testing centers. Future interventions, including delabeling the counseling and testing centers and demonstrating the efficacy of highly active antiretroviral therapy, will be critical in reducing the stigma of HIV/AIDS in communities.
Mild Hypothermia as a Cardioprotective Approach for Acute Myocardial Infarction: Laboratory to Clinical Application
Authors: Hale Sharon L. , Kloner Robert A.
Published: December 2010

In many animal models, mild therapeutic hypothermia is a powerful intervention, reducing myocardial infarct size, reducing the no-reflow phenomenon, and improving healing after infarction. Cooling in these models has been produced by various means including whole-body hypothermia, synchronized hypothermic coronary venous retro-perfusion, heat exchangers, and regional hypothermia targeting the heart alone. However, in humans, the most widely used techniques are surface cooling and cooling by endovascular heat-exchange catheters. The reduction in temperature necessary to produce cardioprotection is mild (32-34°C), appears to have no detrimental effects on left ventricular function or regional myocardial blood flow, and may improve microvascular reflow to previously ischemic heart tissue. It has been shown in experimental and clinical studies that for therapeutic hypothermia to be effective it must be (1) initiated as early as possible after the onset of ischemia and (2) initiated before reperfusion. This may require initiation of hypothermia in the ambulance, well before mechanical reperfusion occurs. The mechanisms of protection produced by hypothermia have yet to be conclusively determined but may include a decrease in tissue metabolic rate, preservation of high energy phosphates, a reduction in tissue apoptosis or induction of heat shock proteins.
Chronic Treatment WithN-acetylcysteine Improves Cardiac Function but Does Not Prevent Progression of Cardiomyopathy in Syrian Cardiomyopathic Hamsters
Authors: Crespo María J. , Cruz Nildris , Altieri Pablo I. , Escobales Nelson
Published: December 2010

Oxidative stress has been postulated to contribute to the onset and development of heart failure (HF). The efficacy of antioxidant therapy in HF, however, remains controversial. This study evaluates the effect of the antioxidant N-acetylcysteine (NAC, 1 g/kg per day) on cardiovascular function in 2- and 6-month-old Bio-TO2 Syrian cardiomyopathic hamsters (SCH) after treatment for 1 month and 5 months with this drug. Endothelial function, systolic blood pressure (SBP), and echocardiographic parameters were evaluated. Age-matched F1-B golden hamsters were used as controls. One month of NAC administration significantly decreased SBP in 2-month-old SCH (n = 5, P < 0.001) without modifying echocardiographic values. Five-month treatment of cardiomyopathic animals with the antioxidant improved the acetylcholine-induced relaxation in aortic rings by 24% (EMaxvalue from 45.8% ± 4% to 55.3% ± 2% n = 7, P < .05) but did not modify EC50values for the acetylcholine concentration-response curve. In addition, 5-month administration of NAC to SCH increased ejection fraction from 39% ± 4% to 57% ± 4% (n = 11, P < .001) and decreased left ventricular end-diastolic and end-systolic volumes (from 0.38 ± 0.04 mL/100 g body weight (BW) and 0.22 ± 0.03 mL/100 g BW, before, to 0.24 ± 0.04 mL/100 g BW and 0.12 ± 0.03 mL/100 g BW after treatment, P < .01). Cardiac output index also improved after 5 months of treatment, although it did not reach statistical significance. These results suggest that antioxidant therapy alone decreases ventricular dilatation and improves cardiovascular function in this animal model of dilated cardiomyopathy, but it does not prevent the appearance of HF.
The Earth Is Not Round (p = .00)
Authors: Cortina Jose M. , Landis Ronald S.
Published: December 2010

Continued discussion and debate regarding the appropriate use of null hypothesis significance testing (NHST) has led to greater reliance on effect size testing (EST) in published literature. This article examines the myth that uncritical replacement of NHST with EST will improve our science. The use of NHST and EST is described along with a summary of the arguments offered in support and against both. After addressing the veracity of these assertions, the article describes the concept of the translation mechanism and compares the success of NHST and EST as mechanisms. Finally, the authors suggest changes that may facilitate translation in future research.
Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition
Authors: Van der Walt Anneke , Stankovich J , Bahlo M , Taylor BV , Van der Mei IAF , Foote SJ , Rubio JP , Kilpatrick TJ , Butzkueven H
Published: December 2010

Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort.

Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients.

Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy.

Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.
Determining minimum standards of living and household budgets
Authors: Deeming Christopher
Published: December 2010

In Australia, sociological research into household budgets and standards of living has long provided a firm basis for policy-makers interested in creating a more inclusive society. The budget approach is, in essence, a simple and intuitive methodology for defining minimum income standards; these include ‘poverty’ thresholds. The budget methodology provides an explicit framework for selecting personal requirements deemed necessary to maintain a particular predefined standard of living. Components are translated through prices into budgets required to purchase them. The last programme of research into household budget standards in Australia is now over a decade old and the work needs to be updated. This is due in part to people’s living standards changing over time, as do their needs. Debates about how best to set minimum social standards are once again popular among social scientists. This article reviews recent methodological developments and issues in budget standards research.
Adolescent experiences of ‘family meals’ in Australia
Authors: Gallegos Danielle , Dziurawiec Suzanne , Fozdar Farida , Abernethie Loraine
Published: December 2010

Popular discourse laments the decline of the ‘family meal’, leading to family fragmentation and nutritional compromise. This article reports findings of a study investigating beliefs and practices surrounding the ‘family meal’, using data drawn from an on-line survey completed by 625 adolescents in Perth, Western Australia. The results challenge current concerns about the loss of the ‘family meal’, demonstrating that, for a majority, meals are eaten together rather than in isolation; are home-made rather than store bought or fast food; and are sites of conversation regardless of the presence of a television. Adolescents are divided, however, on the value of the ‘family meal’, with half seeing it as a positive experience of family togetherness and half regarding it negatively or as unimportant. The findings go some way to dispelling the notion that the ‘family meal’ no longer exists in Australia.
Yoga as a Complementary Therapy for Clinical Depression
Authors: Mehta Purvi , Sharma Manoj
Published: December 2010

Clinical depression is a common illness, with prevalence of current depressive symptoms in the general population of nearly 10% and lifetime diagnosis almost 16%. Yoga offers an attractive option for complementary therapy of depression. The purpose of this study was to examine research regarding the benefits of yoga for depression, to learn to what extent yoga is beneficial as a complementary therapy for this condition. The method used in this study was a systematic qualitative review of interventions obtained from MEDLINE, CINAHL, and ERIC databases. A total of 18 studies met the criteria. Some of the designs utilized by the interventions were pretest posttest, quasi-experimental and randomized controlled trials. It was found that majority of the interventions (17) were able to significantly reduce depressive symptoms in the patients under study. However, several methodological limitations were identified in the conduct of the intervention trials, which future interventions must consider.
Arthroscopic Posterior Cruciate Ligament Tibial Inlay Reconstruction
Authors: Salata Michael J. , Sekiya Jon K.
Published: December 2010

Context:

The reconstruction of isolated complete posterior cruciate ligament (PCL) injuries remains a controversial topic. Proponents for reconstruction cite the premature development of arthritis in the medial and patellofemoral compartments as a compelling reason to offer reconstruction. Currently, no consensus exists about which technique should be used to reconstruct the PCL.

Type of Study:

Surgical technique.

Evidence Acquisition:

A MEDLINE and PUBMED search was performed using the following combination of keywords for the years 1985-2009: PCL, posterior cruciate ligament, and rehabilitation. The reviewed articles were those that addressed rehabilitation of the PCL after reconstruction and were written in the English language.

Results:

This PCL reconstruction technique may be more inherently stable and allow a more progressive rehabilitation program.

Conclusion:

There are unique features of all-arthroscopic, double-bundle, allograft reconstruction of the PCL that allow a more aggressive approach in PCL reconstruction rehabilitation. The stability afforded by the anatomic press-fit tibial plug and the augmented tibial and augmented femoral fixation are a plus. The anatomic position of the tibial insertion avoids the “killer turn” of the transtibial approach, limiting concerns for graft abrasion with range of motion and resultant elongation. The outside-in method for the femoral tunnels also minimizes the abrasion that can occur at the “critical corner.”
Lower Body Stiffness and Muscle Activity Differences Between Female Dancers and Basketball Players During Drop Jumps
Authors: Ambegaonkar Jatin P. , Shultz Sandra J. , Perrin David H. , Schmitz Randy J. , Ackerman Terry A. , Schulz Mark R.
Published: December 2010

Background:

Anterior cruciate ligament (ACL) injuries often occur during landing, with female athletes at higher injury risk than male athletes. Interestingly, female dancers have lower ACL injury rates than do female athletes in general.

Hypothesis:

Female dancers will have earlier and greater lower extremity muscle activity and higher sagittal knee joint and leg stiffness than will female basketball players.

Study Design:

Cross-sectional group comparison.

Methods:

Fifty-five healthy female athletes (35 dancers, 20 basketball players) performed 5 double-leg drop jumps from a 45-cm box. Surface electromyography (onsets and amplitudes; prelanding and postlanding) was recorded from the lateral gastrocnemius, medial and lateral hamstrings, lateral quadriceps muscles with a 3-dimensional electromagnetic tracking system, and forceplates recording biomechanics (leg spring stiffness and knee joint stiffness).

Results:

Compared with basketball players, dancers had greater leg spring stiffness ( P = 0.047) but similar knee joint stiffness ( P = 0.44). Although no significant differences were observed in overall muscle onset times ( P = 0.22) or activation amplitudes (prelanding, P = 0.60; postlanding, P = 0.78), small to moderate effect sizes (ESs) suggest trends in dancers toward earlier (ES = 0.53) and higher medial hamstrings activation pre- (ES = 0.55) and post- (ES = 0.41) landing and lower lateral quadriceps (ES = 0.30) and higher gastrocnemius (ES = 0.33) postlanding muscle activation.

Conclusions:

In dancers, the higher leg spring stiffness and trends toward higher hamstrings prelanding and postlanding, as well as lower quadriceps and higher gastrocnemius activation postlanding with similar knee joint stiffness, indicate lower extremity neuromechanical differences across other joints.

Clinical Relevance:

Female dancers may have lower extremity neuromechanics that are different from those of basketball players during drop jumps. If dancers use ACL-protective strategies during activity, then their training routines should be further investigated to improve ACL injury prevention programs.
Pathophysiology of Sports-Related Concussion
Authors: Giza Christopher C. , DiFiori John P.
Published: December 2010

Context:

Concussions that occur during participation in athletic events affect millions of individuals each year. Although our understanding of the pathophysiology of concussion has grown considerably in recent years, much remains to be elucidated. This article reviews basic science and relevant translational clinical research regarding several aspects of concussion.

Evidence Acquisition:

A literature search was conducted using PubMed from 1966 to 2010, with an emphasis on work published within the past 10 years. Additional articles were identified from the bibliography of recent reviews.

Results:

Basic science and clinical data both indicate that there is a period of increased vulnerability to repeated injury following a concussion and that its duration is variable. Growing evidence indicates that postinjury activity is likely to affect recovery from brain injury. Data suggest that long-term sequelae may result from prior concussion—particularly, repeated injuries. The unique aspects of cerebral development may account for differences in the effects of concussion in children and adolescents when compared with adults.

Conclusions:

The available pathophysiologic data from basic science and clinical studies have increased the evidence base for concussion management strategies—the approaches to which may differ between young athletes and adults.
Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions
Authors: Klimchenko Olena , Di Stefano Antonio , Geoerger Birgit , Hamidi Sofiane , Opolon Paule , Robert Thomas , Routhier Mélanie , El-Benna Jamel , Delezoide Anne-Lise , Boukour Siham , Lescure Bernadette , Solary Eric , Vainchenker William , Norol Françoise
Published: December 2010

The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14lowCD16− precursor to form CD14highCD16+ cells without producing the CD14highCD16− cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.
Therapeutic levels of fetal hemoglobin in erythroid progeny of β-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer
Authors: Wilber Andrew , Hargrove Phillip W. , Kim Yoon-Sang , Riberdy Janice M. , Sankaran Vijay G. , Papanikolaou Eleni , Georgomanoli Maria , Anagnou Nicholas P. , Orkin Stuart H. , Nienhuis Arthur W. , Persons Derek A.
Published: December 2010

β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α2β2;HbA). Increased levels of fetal hemoglobin (α2γ2;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34+ cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with β-thalassemia major. Lentiviral vectors encoding (1) a human γ-globin gene with or without an insulator, (2) a synthetic zinc-finger transcription factor designed to interact with the γ-globin gene promoters, or (3) a short-hairpin RNA targeting the γ-globin gene repressor, BCL11A, were tested. Erythroid progeny of normal CD34+ cells demonstrated levels of HbF up to 21% per vector copy. For β-thalassemic CD34+ cells, similar gene transfer efficiencies achieved HbF production ranging from 45% to 60%, resulting in up to a 3-fold increase in the total cellular Hb content. These observations suggest that both lentiviral-mediated γ-globin gene addition and genetic reactivation of endogenous γ-globin genes have potential to provide therapeutic HbF levels to patients with β-globin deficiency.
Zonation for 3D aquifer characterization based on joint inversions of multimethod crosshole geophysical data
Authors: Doetsch Joseph , Linde Niklas , Coscia Ilaria , Greenhalgh Stewart A. , Green Alan G.
Published: December 2010

Predictive groundwater modeling requires accurate information about aquifer characteristics. Geophysical imaging is a powerful tool for delineating aquifer properties at an appropriate scale and resolution, but it suffers from problems of ambiguity. One way to overcome such limitations is to adopt a simultaneous multitechnique inversion strategy. We have developed a methodology for aquifer characterization based on structural joint inversion of multiple geophysical data sets followed by clustering to form zones and subsequent inversion for zonal parameters. Joint inversions based on cross-gradient structural constraints require less restrictive assumptions than, say, applying predefined petrophysical relationships and generally yield superior results. This approach has, for the first time, been applied to three geophysical data types in three dimensions. A classification scheme using maximum likelihood estimation is used to determine theparameters of a Gaussian mixture model that defines zonal geometries from joint-inversion tomograms. The resulting zones are used to estimate representative geophysical parameters of each zone, which are then used for field-scale petrophysical analysis. A synthetic study demonstrated how joint inversion of seismic and radar traveltimes and electrical resistance tomography (ERT) data greatly reduces misclassification of zones (down from 21.3% to 3.7%) and improves the accuracy of retrieved zonal parameters (from 1.8% to 0.3%) compared to individual inversions. We applied our scheme to a data set collected in northeastern Switzerland to delineate lithologic subunits within a gravel aquifer. The inversion models resolve three principal subhorizontal units along with some important 3D heterogeneity. Petrophysical analysis of the zonal parameters indicated approximately 30% variation in porosity within the gravel aquifer and an increasing fraction of finer sediments with depth.