bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of metallothionein 1 and 2 does not affect atrophy or oxidant activity in a novel in vitro model
Authors: Hyldahl Robert D. , O'Fallon Kevin S. , Schwartz Lawrence M. , Clarkson Priscilla M.
Published: August 2010

Skeletal muscle atrophy is a significant health problem that results in decreased muscle size and function and has been associated with increases in oxidative stress. The molecular mechanisms that regulate muscle atrophy, however, are largely unknown. The metallothioneins (MT), a family of genes with antioxidant properties, have been found to be consistently upregulated during muscle atrophy, although their function during muscle atrophy is unknown. Therefore, we hypothesized that MT knockdown would result in greater oxidative stress and an enhanced atrophy response in C2C12 myotubes subjected to serum reduction (SR), a novel atrophy-inducing stimulus. Forty-eight hours before SR, myotubes were transfected with small interfering RNA (siRNA) sequences designed to decrease MT expression. Muscle atrophy and oxidative stress were then measured at baseline and for 72 h following SR. Muscle atrophy was quantified by immunocytochemistry and myotube diameter measurements. Oxidative stress was measured using the fluorescent probe 5-(and-6)-carboxy-2′,7′-dichlorodihydrofluorescein. SR resulted in a significant increase in oxidative stress and a decrease in myotube size and protein content. However, there were no differences observed in the extent of muscle atrophy or oxidant activity following MT knockdown. We therefore conclude that the novel SR model results in a strong atrophy response and an increase in oxidant activity in cultured myotubes and that knockdown of MT does not affect that response.
P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the exercise pressor reflex
Authors: McCord Jennifer L. , Tsuchimochi Hirotsugu , Kaufman Marc P.
Published: August 2010

The exercise pressor reflex is due to activation of thin fiber afferents within contracting muscle. These afferents are in part stimulated by ATP activation of purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes are good candidates because they are located on thin fiber afferents and are involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors evoke the metabolic component of the exercise pressor reflex, we examined the effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10 mg/kg), on the pressor response to injections of α,β-methylene ATP (α,β-MeATP; 50 μg/kg), freely perfused static contraction, contraction of the triceps surae muscles while the circulation was occluded, and postcontraction circulatory occlusion in decerebrate cats. We found that the antagonists reduced the pressor response to α,β-MeATP injection (before Δ 20 ± 3 mmHg; drug Δ 11 ± 3 mmHg; P < 0.05), suggesting the antagonists were effective in blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the pressor response to freely perfused contraction (before Δ 33 ± 5 mmHg; drug Δ 15 ± 5 mmHg; P < 0.05), contraction with the circulation occluded (before Δ 52 ± 7 mmHg; drug Δ 20 ± 4 mmHg; P < 0.05), and during postcontraction circulatory occlusion (before Δ 15 ± 1 mmHg; drug Δ 5 ± 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors contribute to the metabolic component of the exercise pressor reflex in decerebrate cats.
A Combination of Serum Markers for the Early Detection of Colorectal Cancer
Authors: Wild Norbert , Andres Herbert , Rollinger Wolfgang , Krause Friedemann , Dilba Peter , Tacke Michael , Karl Johann
Published: August 2010

Purpose: Fecal occult blood testing is recommended as first-line screening to detect colorectal cancer (CRC). We evaluated markers and marker combinations in serum as an alternative to improve the detection of CRC.

Experimental Design: Using penalized logistic regression, 6 markers were selected for evaluation in 1,027 samples (301 CRC patients, 143 patients with adenoma, 266 controls, 141 disease controls, and 176 patients with other cancer). The diagnostic performance of each marker and of marker combinations was assessed.

Results: To detect CRC from serum samples, we tested 22 biomarkers. Six markers were selected for a marker combination, including the known tumor markers CEA (carcinoembryonic antigen) and CYFRA 21-1 as well as novel markers or markers that are less routinely used for the detection of CRC: ferritin, osteopontin (OPN), anti-p53, and seprase. CEA showed the best sensitivity at 95% specificity with 43.9%, followed by seprase (42.4%), CYFRA 21-1 (35.5%), OPN (30.2%), ferritin (23.9%), and anti-p53 (20.0%). A combination of these markers gave 69.6% sensitivity at 95% specificity and 58.7% at 98% specificity. Focusing on International Union against Cancer (UICC) stages 0–III reduced the sensitivity slightly to 68.0% and 53.3%, respectively. In a subcollective, with matched stool samples (75 CRC cases and 234 controls), the sensitivity of the marker combination was comparable with fecal immunochemical testing (FIT) with 82.4% and 68.9% versus 81.8% and 72.7% at 95% and 98% specificity, respectively.

Conclusions: The performance of the serum marker combination is comparable with FIT. This provides a novel tool for CRC screening to trigger a follow-up colonoscopy for a final diagnosis. Clin Cancer Res; 16(24); 6111–21. ©2010 AACR.
Human Umbilical Cord Blood–Derived Endothelial Cells Reendothelialize Vein Grafts and Prevent Thrombosis
Authors: Brown Melissa A. , Zhang Lisheng , Levering Vrad W. , Wu Jiao-Hui , Satterwhite Lisa L. , Brian Leigh , Freedman Neil J. , Truskey George A.
Published: August 2010

Objective—

To accelerate vein graft reendothelialization and reduce vein graft thrombosis by infusing human umbilical cord blood–derived endothelial cells (hCB-ECs) because loss of endothelium contributes to vein graft thrombosis and neointimal hyperplasia.

Methods and Results—

Under steady flow conditions in vitro, hCB-ECs adhered to smooth muscle cells 2.5 to 13 times more than ECs derived from peripheral blood or human aorta (
P
<0.05). Compared with peripheral blood and human aorta ECs, hCB-ECs had 1.4-fold more cell surface α
5
β
1
integrin heterodimers per cell (
P
<0.05) and proliferated on fibronectin 4- to 10-fold more rapidly (
P
<0.05). Therefore, we used hCB-ECs to enhance reendothelialization of carotid interposition vein grafts implanted in NOD.CB17-Prkdc
scid
/J mice. Two weeks postoperatively, vein grafts from hCB-EC–treated mice demonstrated approximately 55% reendothelialization and no luminal thrombosis. In contrast, vein grafts from sham-treated mice demonstrated luminal thrombosis in 75% of specimens (
P
<0.05) and only approximately 14% reendothelialization. In vein grafts from hCB-EC–treated mice, 33±10% of the endothelium was of human origin, as judged by human major histocompatibility class I expression.

Conclusion—

The hCB-ECs adhere to smooth muscle cells under flow conditions in vitro, accelerate vein graft reendothelialization in vivo, and prevent vein graft thrombosis. Thus, hCB-ECs offer novel therapeutic possibilities for vein graft disease.
Application of the Seattle Heart Failure Model in Ambulatory Patients Presented to an Advanced Heart Failure Therapeutics Committee
Authors: Gorodeski Eiran Z. , Chu Eric C. , Chow Chen H. , Levy Wayne C. , Hsich Eileen , Starling Randall C.
Published: August 2010

Background—

We sought to assess the predictive value of the Seattle Heart Failure Model (SHFM) when applied to ambulatory patients with advanced heart failure (HF) presented to an advanced HF therapeutics committee at a tertiary care US institution.

Methods and Results—

We evaluated model discrimination and calibration in 215 consecutive ambulatory patients who were presented to the Cleveland Clinic advanced HF therapeutics committee between 2004 to 2007 for evaluation for advanced options including transplantation and ventricular assist device (VAD). Analyses were stratified by committee decision (not listed versus listed United Network of Organ Sharing [UNOS] Status 2). Eighty-five percent had 1 or no missing SHFM variables. The primary outcome was a composite of all-cause mortality, VAD, or urgent (UNOS Status 1) transplantation. During a median follow-up of 24 months, 68 died, 18 received VAD support, and 81 underwent heart transplantation. Discrimination was modest both for those not listed (c-index, 0.683 at 1 year and 0.648 at 2 years), and for those listed UNOS status 2 (c-index, 0.629 at 1 year and 0.628 at 2 years). Calibration was acceptable among those patients not listed for heart transplantation but with substantial underestimation of risk (ie, overestimation of survival free of VAD or urgent transplantation) among UNOS status 2 patients.

Conclusions—

In ambulatory patients presented to an advanced HF therapeutics committee for evaluation for heart transplantation, the SHFM offers modest discrimination of risk for the primary composite outcome of mortality, VAD, or urgent transplantation, with underestimation of risk in those patients listed for nonurgent transplantation. Interpretation of risk prediction by the SHFM in this patient population must be done with caution.
High von Willebrand Factor Levels Increase the Risk of Stroke
Authors: Wieberdink Renske G. , van Schie Marianne C. , Koudstaal Peter J. , Hofman Albert , Witteman Jacqueline C.M. , de Maat Moniek P.M. , Leebeek Frank W.G. , Breteler Monique M.B.
Published: August 2010

Background and Purpose—

Many studies have investigated the role of plasma von Willebrand factor level in coronary heart disease, but few have investigated its role in stroke. The aim of this study was to determine if von Willebrand factor levels are associated with the risk of stroke.

Methods—

The study was part of the Rotterdam Study, a large population-based cohort study among subjects aged ≥55 years. We included 6 250 participants who were free from stroke at baseline (1997 to 2001) and for whom blood samples were available. Follow-up for incident stroke was complete up to January 1, 2005. Data were analyzed with Cox proportional hazards models adjusted for age and sex and additionally with models adjusted for other potential confounders including ABO blood group. A subgroup analysis was performed in participants without atrial fibrillation. Effect modification by sex was tested on a multiplicative and on an additive scale.

Results—

During an average follow-up time of 5.0 years, 290 first-ever strokes occurred, of which 197 were classified as ischemic. The risk of stroke increased with increasing von Willebrand factor levels (age- and sex-adjusted hazard ratios per SD increase in von Willebrand factor level: 1.12 [95% CI, 1.01 to 1.25] for stroke, 1.13 [95% CI, 0.99 to 1.29] for ischemic stroke). Adjustments for additional confounders slightly attenuated the association. The association was also present in subjects without atrial fibrillation and did not differ between sexes.

Conclusion—

High von Willebrand factor levels are associated with stroke risk in the general population.
Isolated Vein Thrombosis of the Posterior Fossa Presenting as Localized Cerebellar Venous Infarctions or Hemorrhages
Authors: Ruiz-Sandoval José L. , Chiquete Erwin , Navarro-Bonnet Jorge , Ochoa-Guzmán Ana , Arauz-Góngora Antonio , Barinagarrementería Fernando , Cantú Carlos
Published: August 2010

Background and Purpose—

Cerebellar venous infarction or hemorrhage due to isolated venous thrombosis of the posterior fossa is a rare form of intracranial vein thrombosis that can be unsuspected in clinical practice.

Methods—

We studied 230 patients with intracranial vein thrombosis, identifying 9 (3.9%: 7 women, mean age 34 years) with neuroimaging or histopathologic evidence of localized posterior fossa vein thrombosis causing parenchymal injury limited exclusively to the cerebellum.

Results—

All patients had an insidious presentation suggesting other diagnoses. Intracranial hypertension (n=6) and cerebellar (n=4) syndromes were the main clinical presentations. Intracranial vein thrombosis was idiopathic in 3 patients; associated with puerperium in 3; and with contraceptives, protein C deficiency, and dehydration in 1 case each. CT was abnormal but not diagnostic in 5 patients, showing a cerebellar hypodensity with fourth ventricle compression and variable hydrocephalus in 5 patients, and cerebellar hemorrhage in 2. Conventional MRI provided diagnosis in 6 cases, showing the causal thrombosis and cerebellar involvement; angiography was practiced in 2 of them, confirming the findings identified by MRI. In the other 3 patients, diagnosis was reached by histopathology. Thromboses were localized at the straight sinus (n=4), lateral sinuses (n=3), and superior petrosal vein (n=2). The acute case fatality rate was 22.2% (n=2), 1 (11.1%) patient was discharged in a vegetative state, 1 (11.1%) was severely disabled, and 5 (55.6%) were moderately disabled.

Conclusions—

Isolated venous thrombosis of the posterior fossa is infrequent and implies a challenging diagnosis. Risk factors for intracranial vein thrombosis and atypical cerebellar findings on CT should lead to further MRI assessment.
Association Between Basilar Artery Hypoplasia and Undetermined or Lacunar Posterior Circulation Ischemic Stroke
Authors: Olindo Stephane , Khaddam Saad , Bocquet Jonathan , Chausson Nicolas , Aveillan Mathieu , Cabre Philippe , Smadja Didier
Published: August 2010

Background and Purpose—

The aim of the current study was to determine the prevalence of basilar artery hypoplasia (BAH) and to evaluate whether BAH is a possible risk factor for posterior circulation stroke (PCS).

Methods—

Basilar artery diameter was assessed by MRI in 685 consecutive ischemic stroke patients. BAH frequency, defined as a diameter <2 mm, was measured and compared between anterior circulation stroke and PCS groups.

Results—

Thirty-seven patients had BAH (5.2%): 15 of 195 (7.7%) in PCS and 22 of 490 (4.5%) in anterior circulation stroke (
P
=0.2). In undetermined or lacunar stroke patients, BAH frequency was higher in PCS than in anterior circulation stroke (14/97, 14.4% vs 10/216, 4.6%;
P
=0.005). National Institutes of Health Stroke Scale score was <4 in 65%. Localization of stroke was predominant in pons or cerebellar territories (71.4%). Half of PCS and BAH patients showed small pontic-penetrating arteries infarcts.

Conclusions—

Our study suggests that BAH is associated with PCS in lacunar or undetermined stroke. Patients often had minor stroke and infarctions that were usually small and frequently located in pontine-penetrating artery territories.
Pairing Research Questions and Theories of Genre: A Case Study of the Hodayot
Authors: Newsom Carol A.
Published: August 2010

No single model of genre is adequate to inform all types of research questions. In this article six approaches to genre are briefly described. Then each is discussed in relation to how it has been or might be used in investigating the Qumran Hodayot.
Joining the Club: A Suggestion about Genre in Early Jewish Texts
Authors: Wright Benjamin G. III
Published: August 2010

Biblical studies has traditionally worked with a classificatory or definitional approach to genre. Recent scholarship in genre studies, however, has pointed out the shortcomings of a classificatory system. Among the different theories about genre that are current in genre studies, prototype theory, derived from advances in cognitive science, offers the possibility for thinking differently about genre as a classificatory tool and about what questions we want considerations of genre to answer. Rather than listing necessary features, prototype theory focuses on the way that humans categorize through the use of prototypical exemplars that reflect an idealized cognitive model of a category. Within this approach, genres have indeterminate boundaries and can be extended to include marginal or atypical examples. This paper takes up the categories of apocalyptic and wisdom as examples of how prototype theory can be used to describe a genre, to provide a more effective way to accommodate what are usually thought of as problematic cases, and to think about the generic relations of texts to one another.
Genre Theory, Rewritten Bible and Pesher
Authors: Brooke George J.
Published: August 2010

This article considers how the wide range of compositions from the Second Temple period that represent or depend implicitly or explicitly on some form of authoritative Jewish scripture should be suitably described and categorized. Three broad sets of issues are addressed. The first concerns how the “authority” of texts or textual traditions within particular groups of texts should be articulated suitably, particularly in relation to the respective roles for form, content and function in such articulations. The second concerns the role that should be played by reflections on the hierarchy of genres, generic instability, and evolutionary models of genre construction in how it is appropriate to distinguish earlier from later, or authoritative from dependent, primary from secondary compositions. The third concerns what labels might suitably be imposed on this broad range of literature, a breadth of literary compositions that seldom makes plain how it understands itself. The questions are addressed by the open-ended definition of the corpus to be studied, by consideration of the problems surrounding the criteria for generic definition, by reviewing the perspectives derived from thinking about the evolution of genres, and by giving some place to the need for cross-cultural analogies. A concluding section asks diachronic and synchronic questions about anthologies of authoritative texts and their interpretations.
The Epistle of Enoch: Genre and Authorial Presentation
Authors: Stuckenbruck Loren T.
Published: August 2010

To the extent that a writing openly presents itself as the result of authorial activity, discussions of genre cannot dispense with the question of how, formally, communication occurs. Taking the Epistle of Enoch and Apocalypse of Weeks in 1 Enochas the points of departure, the present essay attempts to show that a discussion of what a document declares about its own writtenness opens up a way of understanding it in comparison to other documents that do the same along analogous lines, whether sapiential or apocalyptic.
Impact of Cloud-Nucleating Aerosols in Cloud-Resolving Model Simulations of Warm-Rain Precipitation in the East China Sea
Authors: Saleeby Stephen M. , Berg Wesley , van den Heever Susan , L’Ecuyer Tristan
Published: August 2010

Cloud-nucleating aerosols emitted from mainland China have the potential to influence cloud and precipitation systems that propagate through the region of the East China Sea. Both simulations from the Spectral Radiation-Transport Model for Aerosol Species (SPRINTARS) and observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) reveal plumes of pollution that are transported into the East China Sea via frontal passage or other offshore flow. Under such conditions, satellite-derived precipitation estimates from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and Precipitation Radar (PR) frequently produce discrepancies in rainfall estimates that are hypothesized to be a result of aerosol modification of cloud and raindrop size distributions. Cloud-resolving model simulations were used to explore the impact of aerosol loading on three identified frontal-passage events in which the TMI and PR precipitation estimates displayed large discrepancies. Each of these events was characterized by convective and stratiform elements in association with a frontal passage. Area-averaged time series for each event reveal similar monotonic cloud and rain microphysical responses to aerosol loading. The ratio in the vertical distribution of cloud water to rainwater increased. Cloud droplet concentration increased and the mean diameters decreased, thereby reducing droplet autoconversion and collision–coalescence growth. As a result, raindrop concentration decreased, while the drop mean diameter increased; furthermore, average rainwater path magnitude and area fraction both decreased. The average precipitation rate fields reveal a complex modification of the timing and spatial coverage of rainfall. This suggests that the warm-rain microphysical response to aerosols, in addition to the precipitation life cycle, microphysical feedbacks, and evaporative effects, play an important role in determining surface rainfall.
Quantifying Differences in Circulation Patterns Based on Probabilistic Models: IPCC AR4 Multimodel Comparison for the North Atlantic*
Authors: Rust Henning W. , Vrac Mathieu , Lengaigne Matthieu , Sultan Benjamin
Published: August 2010

The comparison of circulation patterns (CPs) obtained from reanalysis data to those from general circulation model (GCM) simulations is a frequent task for model validation, downscaling of GCM simulations, or other climate change–related studies. Here, the authors suggest a set of measures to quantify the differences between CPs. A combination of clustering using Gaussian mixture models with a set of related difference measures allows for taking cluster size and shape information into account and thus provides more information than the Euclidean distances between cluster centroids. The characteristics of the various distance measures are illustrated with a simple simulated example. Subsequently, a five-component Gaussian mixture to define circulation patterns for the North Atlantic region from reanalysis data and GCM simulations is used. CPs are obtained independently for the NCEP–NCAR reanalysis and the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40), as well as for twentieth-century simulations from 14 GCMs of the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) database. After discussing the difference of CPs based on spherical and nonspherical clusters for the reanalysis datasets, the authors give a detailed evaluation of the cluster configuration for two GCMs relative to NCEP–NCAR. Finally, as an illustration, the capability of reproducing the NCEP–NCAR probability density function (pdf) defining the Greenland anticyclone CP is evaluated for all 14 GCMs, considering that the size and shape of the underlying pdfs complement the commonly used Euclidean distance of CPs’ mean values.
Two Limits of Initial-Value Decadal Predictability in a CGCM
Authors: Branstator Grant , Teng Haiyan
Published: August 2010

When the climate system experiences time-dependent external forcing (e.g., from increases in greenhouse gas and aerosol concentrations), there are two inherent limits on the gain in skill of decadal climate predictions that can be attained from initializing with the observed ocean state. One is the classical initial-value predictability limit that is a consequence of the system being chaotic, and the other corresponds to the forecast range at which information from the initial conditions is overcome by the forced response. These limits are not caused by model errors; they correspond to limits on the range of useful forecasts that would exist even if nature behaved exactly as the model behaves. In this paper these two limits are quantified for the Community Climate System Model, version 3 (CCSM3), with several 40-member climate change scenario experiments. Predictability of the upper-300-m ocean temperature, on basin and global scales, is estimated by relative entropy from information theory. Despite some regional variations, overall, information from the ocean initial conditions exceeds that from the forced response for about 7 yr. After about a decade the classical initial-value predictability limit is reached, at which point the initial conditions have no remaining impact. Initial-value predictability receives a larger contribution from ensemble mean signals than from the distribution about the mean. Based on the two quantified limits, the conclusion is drawn that, to the extent that predictive skill relies solely on upper-ocean heat content, in CCSM3 decadal prediction beyond a range of about 10 yr is a boundary condition problem rather than an initial-value problem. Factors that the results of this study are sensitive and insensitive to are also discussed.
Understanding the Daily Cycle of Evapotranspiration: A Method to Quantify the Influence of Forcings and Feedbacks
Authors: van Heerwaarden Chiel C. , Vilà-Guerau de Arellano Jordi , Gounou Amanda , Guichard Françoise , Couvreux Fleur
Published: August 2010

A method to analyze the daily cycle of evapotranspiration over land is presented. It quantifies the influence of external forcings, such as radiation and advection, and of internal feedbacks induced by boundary layer, surface layer, and land surface processes on evapotranspiration. It consists of a budget equation for evapotranspiration that is derived by combining a time derivative of the Penman–Monteith equation with a mixed-layer model for the convective boundary layer. Measurements and model results for days at two contrasting locations are analyzed using the method: midlatitudes (Cabauw, Netherlands) and semiarid (Niamey, Niger). The analysis shows that the time evolution of evapotranspiration is a complex interplay of forcings and feedbacks. Although evapotranspiration is initiated by radiation, it is significantly regulated by the atmospheric boundary layer and the land surface throughout the day. In both cases boundary layer feedbacks enhance the evapotranspiration up to 20 W m−2 h−1. However, in the case of Niamey this is offset by the land surface feedbacks since the soil drying reaches −30 W m−2 h−1. Remarkably, surface layer feedbacks are of negligible importance in a fully coupled system. Analysis of the boundary layer feedbacks hints at the existence of two regimes in this feedback depending on atmospheric temperature, with a gradual transition region in between the two. In the low-temperature regime specific humidity variations induced by evapotranspiration and dry-air entrainment have a strong impact on the evapotranspiration. In the high-temperature regime the impact of humidity variations is less pronounced and the effects of boundary layer feedbacks are mostly determined by temperature variations.
Regional Extreme Monthly Precipitation Simulated by NARCCAP RCMs
Authors: Gutowski William J. , Arritt Raymond W. , Kawazoe Sho , Flory David M. , Takle Eugene S. , Biner Sébastien , Caya Daniel , Jones Richard G. , Laprise René , Leung L. Ruby , Mearns Linda O. , Moufouma-Okia Wilfran , Nunes Ana M. B. , Qian Yun , Roads John O. , Sloan Lisa C. , Snyder Mark A.
Published: August 2010

This paper analyzes the ability of the North American Regional Climate Change Assessment Program (NARCCAP) ensemble of regional climate models to simulate extreme monthly precipitation and its supporting circulation for regions of North America, comparing 18 years of simulations driven by the National Centers for Environmental Prediction (NCEP)–Department of Energy (DOE) reanalysis with observations. The analysis focuses on the wettest 10% of months during the cold half of the year (October–March), when it is assumed that resolved synoptic circulation governs precipitation. For a coastal California region where the precipitation is largely topographic, the models individually and collectively replicate well the monthly frequency of extremes, the amount of extreme precipitation, and the 500-hPa circulation anomaly associated with the extremes. The models also replicate very well the statistics of the interannual variability of occurrences of extremes. For an interior region containing the upper Mississippi River basin, where precipitation is more dependent on internally generated storms, the models agree with observations in both monthly frequency and magnitude, although not as closely as for coastal California. In addition, simulated circulation anomalies for extreme months are similar to those in observations. Each region has important seasonally varying precipitation processes that govern the occurrence of extremes in the observations, and the models appear to replicate well those variations.
Ideology, Crisis Intensity, Organizational Demography, and Industrial Type as Determinants of Organizational Change in Kibbutzim
Authors: Sheaffer Zachary , Honig Benson , Carmeli Abraham
Published: August 2010

Kibbutzim were a pure missionary organization known for their egalitarian—communal lifestyle. However, like many other organizational forms, the kibbutz model has been subjected to significant pressures to become more market oriented. This challenges the existence of kibbutzim in many ways. Stressing ideological homogeneity as a key predictor of change, this study also examines the effect of crisis as assessed by financial distress, demographic depletion, and type of manufacturing industry, on change intensity. Using a sample of 171 kibbutzim over a 7 year-period, the findings indicate consistent effects of ideology, crisis intensity, demographic depletion, and organizational size on change intensity. Theoretical implications for atypical organizations are discussed.
Use of Evidence-Based Therapy for the Prevention of Cardiovascular Events Among Older people
Authors: Castelino Ronald L. , Chen Timothy F. , Guddattu Vasudev , Bajorek Beata V.
Published: August 2010

Evidence-based therapies (EBTs) for the prevention of cardiovascular disease (CVD) are reportedly underutilized in older people. The primary purpose of this study was to evaluate the use of EBTs for the prevention of CVD events in older people and secondarily whether a Home Medicines Review (HMR) service by pharmacists’ predicts the use of these medicines. A retrospective cross-sectional audit of HMR reports pertaining to 608 community-dwelling older people (≥65 years) was conducted. EBTs considered for this audit included four guideline-recommended therapies for CVD: antithrombotic therapy (warfarin ± antiplatelet therapy), β-blockers, statins, and angiotensin agents (angiotensin-converting enzyme inhibitors [ACEI] ± angiotensin II receptor blockers [ARBs]). The prevalence of EBT use among the older people, mean age (SD) 75.6 (7.5) years, was: 73% for antithrombotic therapy, 75% for statins, 74% for angiotensin therapy, and 35% for β-blockers. CVD risk factors warranting treatment with these EBTs were frequently associated with use of EBTs. EBTs were least likely to be used in those with coronary interventions like coronary artery bypass grafting (CABG)/stent insertion (all EBTs except angiotensin agents) and angiotensin agents in those with a history of myocardial infarction or chronic heart failure. A pharmacist-led HMR service was significantly associated with the prescribing of all 4 EBTs. The results from this study show good adherence to evidence-based guidelines in general, although there is still room for improvement to further optimize clinical outcomes in these complex patients. The study also adds to the available literature on the effectiveness of pharmacists’ collaborative contribution to the care of these high-risk patients.
Quality and Coordination of Care for Patients With Multiple Conditions: Results From an International Survey of Patient Experience
Authors: Burgers Jako S. , Voerman Gerlienke E. , Grol Richard , Faber Marjan J. , Schneider Eric C.
Published: August 2010

Previous studies using clinical performance measures suggest that quality of care for patients with multiple chronic conditions is not worse than that for others. This article presents patient-reported experiences of health care among 8,973 of chronically ill adults from eight countries, using telephone survey data. We designed a ‘‘morbidity score’’ combining the number of conditions and reported health status. Respondents with high morbidity scores reported less favorable experience with coordination of care compared to those with low morbidity scores. They also reported lower ratings of overall quality of care. There were no differences in reported experience with the individual physicians. Comparing type of comorbidity, chronic lung, and mental health problems were associated with lower ratings than hypertension, heart disease, diabetes, arthritis, and cancer. The implications and limitations of this study are discussed in the context of health care reform. Pay-for-performance programs need to account for chronic conditions to avoid penalizing physicians who care for larger shares of such patients.
Hidden Legacies. S.H. Foulkes, Kurt Goldstein and Ernst Cassirer
Authors: Nitzgen Dieter
Published: August 2010

Apart from being himself a creative and prolific writer, Malcolm Pines has also been an important editor of group analytic writings. In that role, he has generously encouraged, furthered and tutored a good many group analysts in their own efforts to write (including myself). As an editor, a particular focus and concern of Malcolm’s have been the writings of S.H. Foulkes, which he tirelessly sought to make public and to promote— and which, after all, was never an easy task from the beginning. The following article has been written to honour this huge editorial effort, its intellectual rigour and underlying eros. In it, I shall (re)approach Foulkes’ early review of Kurt Goldstein’s The Organism (1934), one of his lesser known articles which was to appear in English only after Foulkes’ death. Translated and abridged by E. Foulkes and introduced by M. Pines, it missed some of the nuances of the German original, and thus important traces regarding the scientific background of Foulkes’ work, especially the legacy of Goldstein’s cousin, the philosopher E. Cassirer.
Dare we speak of ethics? Attending to the unsayable amongst nurse leaders
Authors: Schick Makaroff Kara , Storch Janet , Newton Lorelei , Fulton Tom , Stevenson Lynne
Published: August 2010

There is increasing emphasis on the need for collaboration between practice and academic leaders in health care research. However, many problems can arise owing to differences between academic and clinical goals and timelines. In order for research to move forward it is important to name and address these issues early in a project. In this article we use an example of a participatory action research study of ethical practice in nursing to highlight some of the issues that are not frequently discussed and we identify the impact of things not-named. Further, we offer our insights to others who wish to be partners in research between academic and practice settings. These findings have wide implications for ameliorating misunderstandings that may develop between nurse leaders in light of collaborative research, as well as for participatory action research.
The Complexity of the Treatment: The Decision-Making Process Among Women With Rheumatoid Arthritis
Authors: Salt Elizabeth , Peden Ann
Published: August 2010

There are effective medications available for the treatment of rheumatoid arthritis (RA); yet, medication adherence remains a problem. In this study, grounded theory methodology was used to investigate the decision-making process used by 30 women with RA when deciding to participate in an evidence-based treatment regimen for this disease. From the study findings, a four-phase process was identified. Pain, life functioning, and exhaustion of health care resources are the components of the initial phase, decision initiation. During knowledge acquisition, the second phase, patients attain information about RA and medications used for its treatment from varying sources. The third phase, trusting the health care provider, is defined by a trusting relationship between patients and health care providers. Patients decide to take or not take medications for RA during the final phase, decision is made. The participating women with RA used a complex decision-making process when deciding to take medications for this disease.
Exploring Relationships Among Psychosocial Status, Dietary Quality, and Measures of Placental Development During the First Trimester in Low-Income Women
Authors: Fowles Eileen R. , Murphey Christina , Ruiz Roberta Jeanne
Published: August 2010

Purpose: To examine the relationships between maternal psychosocial factors and dietary quality and explore the relationships among dietary quality and selected biomarkers of nutrition and placental development. Method: A cross-sectional design in 18 low-income, pregnant women. Results: Partner support was positively related to vegetable intake (r = .54) and negatively related to intake of iron (r = -.68) and grains (r = -.67). Emotional eating in response to anger was negatively related to intake of iron-(r /it> = -.53) and folate-rich (r = -.75) foods, and emotional eating in response to anxiety was negatively related to intake of folate-rich foods (r = -.51). Depressed women had an increased intake of calcium-rich foods (r = .60). Levels of vascular endothelial growth factor (VEGF) were negatively related to depression (r = -.56) and intake of foods high in calcium (r = -.53) and iron (r = -.34) but positively related to serum calcium levels (r = .60). VEGF was negatively relationship to soluble fms-like tyrosine kinase 1 (sFlt-1; r = -.56). Placental growth factor had a negative relationship with maternal serum levels of albumin (r = -.61) and calcium (r = -.65). Conclusions: Low-income pregnant women who eat to cope with anger and anxiety may have an inadequate intake of nutrients that contribute to positive pregnancy outcomes. Placental development in the early weeks of pregnancy may be influenced by maternal psychosocial and nutritional status. More research is needed to explore the relationship of dietary quality and placental development in the first trimester of pregnancy.
Introduction to Genetics and Childhood Obesity: Relevance to Nursing Practice
Authors: Seal Nuananong
Published: August 2010

Purpose: The aims for this article are to provide an overview of the current state of research on genetic contributions to the development of childhood obesity and to suggest genetic-focused nursing practices to prevent childhood obesity. Organizing Constructs: Genetic epidemiology of childhood obesity, modes to identifying obesity genes, types of human obesity genes, and nursing implications are discussed. Clinical Relevance: The successful integration of genetics into nursing practice will provide opportunities for nurses to participate fully as major agents and collaborators in the health care revolution. Conclusions: Practicing nurses across the profession will need to become knowledgeable about genetics and take part in obesity prevention through genetic assessment of susceptibility and appropriate environmental interventions.
Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features
Authors: Kumar Shaji , Dispenzieri Angela , Katzmann Jerry A. , Larson Dirk R. , Colby Colin L. , Lacy Martha Q. , Hayman Suzanne R. , Buadi Francis K. , Leung Nelson , Zeldenrust Steve R. , Ramirez-Alvarado Marina , Clark Raynell J. , Kyle Robert A. , Rajkumar S. Vincent , Gertz Morie A.
Published: August 2010

Immunoglobulin free light chains (FLCs) are the precursors of amyloid fibrils in primary amyloidosis (AL). We studied the relationship between FLC levels and clinical features in 730 patients with newly diagnosed AL. The plasma cell clone was λ in 72% patients, and κ in 28% patients. κ-AL had more GI tract and liver involvement, where as renal involvement was more with λ-AL. While the overall survival (OS) was similar for κ and λ-AL, the median OS for those without an identifiable serum heavy chain was significantly shorter (12.6 vs 29.9 months; P = .02). The OS was shorter among those with a higher dFLC (involved FLC−uninvolved FLC; κ > 29.4 mg/dL or λ > 18.2 mg/dL using median for cutoff); 10.9 vs 37.1 months; P < .001. In multivariate analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.
L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions
Authors: Pfeifer Marco , Schirmer Uwe , Geismann Claudia , Schäfer Heiner , Sebens Susanne , Altevogt Peter
Published: August 2010

Background

The L1 cell adhesion molecule (L1CAM) was originally identified as a neural adhesion molecule involved in axon guidance. In many human epithelial carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion and metastasis formation. L1CAM positive carcinomas are associated with bad prognosis. Recent data point out that L1CAM is regulated in a fashion similar to epithelial-mesenchymal transition (EMT). Previous studies have implied the transcription factors Slug and/or β-catenin in L1CAM transcriptional regulation. However, the regulation of human L1CAM expression at the transcriptional level is not well understood.

Results

To better understand the molecular basis of L1CAM transcriptional regulation, we carried out a detailed characterization of the human L1CAM promoter. We identified two transcription start sites, the first in front of a non-translated exon 0 (promoter 1) and the other next to the first protein-coding exon 1 (promoter 2). Both sites could be verified in endometrial carcinoma (EC) cell lines and appear to be used in a cell-type specific manner. The two identified promoter regions showed activity in luciferase reporter assays. Chromatin-IP analyses confirmed the in silico predicted E-boxes, binding sites for transcription factors Snail and Slug, as well as Lef-1 sites, which are related to β-catenin-mediated transcriptional regulation, in both promoters. Overexpression of β-catenin exclusively augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity suggesting that both promoters can be active. Overexpression of β-catenin or Slug could upregulate L1CAM expression in a cell-type specific manner.

Conclusions

Our results, for the first time, provide evidence that the L1CAM gene has two functionally active promoter sites that are used in a cell-type specific manner. Slug and β-catenin are involved L1CAM transcriptional regulation. Nevertheless, Slug rather than β-catenin levels are correlated with L1CAM expression in EC cell lines. Our findings suggest that the L1CAM transcriptional regulation is more complex than anticipated and this study provides the basis for a better understanding of L1CAM regulation in non-neuronal/tumor cells.
TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis
Authors: Bisgin Atil , Terzioglu Ender , Aydin Cigdem , Yoldas Burcak , Yazisiz Veli , Balci Nilufer , Bagci Huseyin , Gorczynski Reginald M , Akdis Cezmi A , Sanlioglu Salih
Published: August 2010

Background

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development.

Methods

The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis.

Results

While no change was detected in the ratio of CD4+to CD8+T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+and CD8+T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+T cells, but not on CD4+T cells, were positively correlated with patients' DAS scores.

Conclusions

Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.
Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion
Authors: Shen Qingli , Cicinnati Vito R , Zhang Xiaoyong , Iacob Speranta , Weber Frank , Sotiropoulos Georgios C , Radtke Arnold , Lu Mengji , Paul Andreas , Gerken Guido , Beckebaum Susanne
Published: August 2010

Background

Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion.

Methods

Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis.

Results

A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells.

Conclusions

Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.
The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis
Authors: Gao Lin-Bo , Pan Xin-Min , Sun Hong , Wang Xia , Rao Li , Li Li-Juan , Liang Wei-Bo , Lv Mei-Li , Yang Wen-Zhong , Zhang Lin
Published: August 2010

Background

Emerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis.

Methods

By searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies.

Results

No significant association between the ATM D1853N polymorphism and breast cancer risk was observed in overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR = 0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively).

Conclusion

Our results indicate that ATM D1853N polymorphism is not a risk factor for developing breast cancer.