bluuebunny/crossref_metadata_2025 huggingface dataset:
Cdkn2a
Is an Atherosclerosis Modifier Locus That Regulates Monocyte/Macrophage Proliferation
Authors: Kuo Chao-Ling , Murphy Andrew J. , Sayers Scott , Li Rong , Yvan-Charvet Laurent , Davis Jaeger Z. , Krishnamurthy Janakiraman , Liu Yan , Puig Oscar , Sharpless Norman E. , Tall Alan R. , Welch Carrie L.
Published: August 2011

Objective—

Common genetic variants in a 58-kb region of chromosome 9p21, near the
CDKN2A/CDKN2B
tumor suppressor locus, are strongly associated with coronary artery disease. However, the underlying mechanism of action remains unknown.

Methods and Results—

We previously reported a congenic mouse model harboring an atherosclerosis susceptibility locus and the region of homology with the human 9p21 locus. Microarray and transcript-specific expression analyses showed markedly decreased
Cdkn2a
expression, including both

p16
INK4a

and

p19
ARF

, but not
Cdkn2b
(

p15
INK4b

), in macrophages derived from congenic mice compared with controls. Atherosclerosis studies in subcongenic strains revealed genetic complexity and narrowed 1 locus to a small interval including
Cdkn2a/b
. Bone marrow (BM) transplantation studies implicated myeloid lineage cells as the culprit cell type, rather than resident vascular cells. To directly test the role of BM-derived
Cdkn2a
transcripts in atherogenesis and inflammatory cell proliferation, we performed a transplantation study using
Cdkn2a
+/−
cells in the
Ldlr
−/−
mouse model.
Cdkn2a
-deficient BM recipients exhibited accelerated atherosclerosis, increased Ly6C
hi
proinflammatory monocytes, and increased monocyte/macrophage proliferation compared with controls.

Conclusion—

These data provide a plausible mechanism for accelerated atherogenesis in susceptible congenic mice, involving decreased expression of
Cdkn2a
and increased proliferation of monocyte/macrophages, with possible relevance to the 9p21 human locus.
Urokinase-Type Plasminogen Activator Deficiency in Bone Marrow–Derived Cells Augments Rupture of Angiotensin II–Induced Abdominal Aortic Aneurysms
Authors: Uchida Haruhito A. , Poduri Aruna , Subramanian Venkateswaran , Cassis Lisa A. , Daugherty Alan
Published: August 2011

Objective—

Abdominal aortic aneurysms (AAAs) are associated with fragmentation of extracellular matrix during development of aortic dilation and rupture. Therefore, it is important to identify specific protease systems involved in extracellular matrix degradation during AAA formation. The present study determined the contribution of the urokinase system to AAA formation and rupture.

Methods and Results—

Angiotensin II (Ang II)–induced AAAs were associated with increased aortic abundance of both urokinase-type plasminogen activator receptor (uPAR) and urokinase-type plasminogen activator (uPA) proteins. However, this increased presence was unrelated to AAA formation because deficiencies of either uPAR or uPA had no effect on either the incidence or size of Ang II–induced AAAs in both normolipidemic mice and low-density lipoprotein receptor−/− mice fed a saturated fat–enriched diet. Although uPA deficiency did not affect development of AAAs, there was an effect of increasing mortality rate from AAA rupture in hypercholesterolemic mice. Bone marrow transplantation demonstrated that enhanced aneurysmal rupture was attributable to deficiency of uPA in leukocytes. uPA deficiency led to an increased propensity for impaired resolution of the thrombotic material within the aneurysmal tissue. Neither uPAR nor uPA deficiency had any effect on Ang II–induced atherosclerosis in low-density lipoprotein receptor−/− mice.

Conclusion—

The uPA-uPAR axis has no effect on the formation of Ang II–induced AAAs, but uPA deficiency promotes aneurysmal rupture.
Regulatory T Cells Limit Vascular Endothelial Injury and Prevent Pulmonary Hypertension
Authors: Tamosiuniene Rasa , Tian Wen , Dhillon Gundeep , Wang Lijuan , Sung Yon K. , Gera Lajos , Patterson Andrew J. , Agrawal Rani , Rabinovitch Marlene , Ambler Kelly , Long Carlin S. , Voelkel Norbert F. , Nicolls Mark R.
Published: August 2011

Rationale:

Pulmonary arterial hypertension (PAH) is an incurable disease associated with viral infections and connective tissue diseases. The relationship between inflammation and disease pathogenesis in these disorders remains poorly understood.

Objective:

To determine whether immune dysregulation due to absent T-cell populations directly contributes to the development of PAH.

Methods and Results:

Vascular endothelial growth factor receptor 2 (VEGFR2) blockade induced significant pulmonary endothelial apoptosis in T-cell-deficient rats but not in immune-reconstituted (IR) rats. T cell–lymphopenia in association with VEGFR2 blockade resulted in periarteriolar inflammation with macrophages, and B cells even prior to vascular remodeling and elevated pulmonary pressures. IR prevented early inflammation and attenuated PAH development. IR with either CD8 T cells alone or with CD4-depleted spleen cells was ineffective in preventing PAH, whereas CD4-depleting immunocompetent euthymic animals increased PAH susceptibility. IR with either CD4
+
CD25
hi
or CD4
+
CD25
−
T cell subsets prior to vascular injury attenuated the development of PAH. IR limited perivascular inflammation and endothelial apoptosis in rat lungs in association with increased FoxP3
+
, IL-10- and TGF-β-expressing CD4 cells, and upregulation of pulmonary bone morphogenetic protein receptor type 2 (BMPR2)–expressing cells, a receptor that activates endothelial cell survival pathways.

Conclusions:

PAH may arise when regulatory T-cell (Treg) activity fails to control endothelial injury. These studies suggest that regulatory T cells normally function to limit vascular injury and may protect against the development of PAH.
B1a B Lymphocytes Are Atheroprotective by Secreting Natural IgM That Increases IgM Deposits and Reduces Necrotic Cores in Atherosclerotic Lesions
Authors: Kyaw Tin , Tay Christopher , Krishnamurthi Surendran , Kanellakis Peter , Agrotis Alex , Tipping Peter , Bobik Alex , Toh Ban-Hock
Published: August 2011

Rationale:

Aggravated atherosclerosis in B lymphocyte-deficient chimeric mice and reduced atherosclerosis after transfer of unfractionated spleen B lymphocytes into splenectomized mice have led to the widely held notion that B lymphocytes are atheroprotective. However, B lymphocytes can be pathogenic, because their depletion by anti-CD20 antibody ameliorated atherosclerosis, and transfer of B2 lymphocytes aggravated atherosclerosis. These observations raise the question of the identity of the atheroprotective B-lymphocyte population.

Objective:

The purpose of the study was to identify an atheroprotective B-lymphocyte subset and mechanisms by which they confer atheroprotection.

Methods and Results:

Splenectomy of apolipoprotein E–deficient mice selectively reduced peritoneal B1a lymphocytes, plasma IgM, and oxidized low-density lipoprotein IgM levels and lesion IgM deposits. These reductions were accompanied by increased oil red O–stained atherosclerotic lesions and increased necrotic cores, oxidized low-density lipoproteins, and apoptotic cells in lesions. Plasma lipids, body weight, collagen, and smooth muscle content were unaffected. Transfer of B1a lymphocytes into splenectomized mice increased peritoneal B1a lymphocytes; restored plasma IgM, oxidized low-density lipoprotein IgM levels, and lesion IgM deposits; and potently attenuated atherosclerotic lesions, with reduced lesion necrotic cores, oxidized low-density lipoprotein, and apoptotic cells. In contrast, transfer of B1a lymphocytes that cannot secrete IgM failed to protect against atherosclerosis development in splenectomized mice despite reconstitution in the peritoneum.

Conclusions:

B1a lymphocytes are an atheroprotective B-lymphocyte population. Our data suggest that natural IgM secreted by these lymphocytes offers protection by depositing IgM in atherosclerotic lesions, which reduces the necrotic cores of lesions.
Transplantation of Human Pericyte Progenitor Cells Improves the Repair of Infarcted Heart Through Activation of an Angiogenic Program Involving Micro-RNA-132
Authors: Katare Rajesh , Riu Federica , Mitchell Kathryn , Gubernator Miriam , Campagnolo Paola , Cui Yuxin , Fortunato Orazio , Avolio Elisa , Cesselli Daniela , Beltrami Antonio Paolo , Angelini Gianni , Emanueli Costanza , Madeddu Paolo
Published: August 2011

Rationale:

Pericytes are key regulators of vascular maturation, but their value for cardiac repair remains unknown.

Objective:

We investigated the therapeutic activity and mechanistic targets of saphenous vein-derived pericyte progenitor cells (SVPs) in a mouse myocardial infarction (MI) model.

Methods and Results:

SVPs have a low immunogenic profile and are resistant to hypoxia/starvation (H/S). Transplantation of SVPs into the peri-infarct zone of immunodeficient CD1/Foxn-1
nu/nu
or immunocompetent CD1 mice attenuated left ventricular dilatation and improved ejection fraction compared to vehicle. Moreover, SVPs reduced myocardial scar, cardiomyocyte apoptosis and interstitial fibrosis, improved myocardial blood flow and neovascularization, and attenuated vascular permeability. SVPs secrete vascular endothelial growth factor A, angiopoietin-1, and chemokines and induce an endogenous angiocrine response by the host, through recruitment of vascular endothelial growth factor B expressing monocytes. The association of donor- and recipient-derived stimuli activates the proangiogenic and prosurvival Akt/eNOS/Bcl-2 signaling pathway. Moreover, microRNA-132 (miR-132) was constitutively expressed and secreted by SVPs and remarkably upregulated, together with its transcriptional activator cyclic AMP response element-binding protein, on stimulation by H/S or vascular endothelial growth factor B. We next investigated if SVP-secreted miR-132 acts as a paracrine activator of cardiac healing. In vitro studies showed that SVP conditioned medium stimulates endothelial tube formation and reduces myofibroblast differentiation, through inhibition of Ras-GTPase activating protein and methyl-CpG-binding protein 2, which are validated miR-132 targets. Furthermore, miR-132 inhibition by antimiR-132 decreased SVP capacity to improve contractility, reparative angiogenesis, and interstitial fibrosis in infarcted hearts.

Conclusion:

SVP transplantation produces long-term improvement of cardiac function through a novel paracrine mechanism involving the secretion of miR-132 and inhibition of its target genes.
Aptamer Neutralization of Beta1-Adrenoceptor Autoantibodies Isolated From Patients With Cardiomyopathies
Authors: Haberland Annekathrin , Wallukat Gerd , Dahmen Claudia , Kage Andreas , Schimke Ingolf
Published: August 2011

Rationale:

Autoantibodies directed against the beta1-adrenoceptor (beta1-AABs) have been proposed to drive the pathogenesis of idiopathic dilated cardiomyoparthy (DCM), Chagas' cardiomyopathy, and peripartum cardiomyopathy. For disease treatment, aptamers that bind and neutralize beta1-AABs could be significant.

Objective:

We determined whether oligonucleotide-aptamers, selected to target human beta1-AABs directed against the second extracellular loop of the beta1-AAB, can neutralize these AABs and modulate their function in vitro.

Methods and Results:

Using Monolex technology, we identified an ssDNA aptamer that targets human beta1-AABs. The neutralization potential of this aptamer against beta1-AABs isolated from patients with DCM, Chagas' cardiomyopathy, and peripartum cardiomyopathy was analyzed using cultured neonatal rat cardiomyocytes by monitoring beta1-AAB induced cell toxicity and chronotropic cell responses. Aptamer addition reduced beta1-AAB induced cell toxicity and neutralized chonotropic beta1-AAB function in a dose-dependent manner. In the presence of aptamer neutralized beta1-AABs, cells remained fully responsive to agonists and antagonists, such as isoprenaline and bisoprolol. Both aptamer pretreated with a complementary (antisense) aptamer and a control scrambled-sequence aptamer were ineffective at beta1-AAB neutralization. Beta1-AABs directed against the first extracellular loop of the beta1-receptor and AABs directed against other G-protein coupled receptors were not affected by the selected aptamer.

Conclusions:

A specific aptamer that can neutralize cardiomyopathy associated human beta1-AABs in vitro has been identified and characterized, providing a framework for future in vivo testing of this treatment option in animal experiments.
Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage
Authors: Naff Neal , Williams Michael A. , Keyl Penelope M. , Tuhrim Stanley , Bullock M. Ross , Mayer Stephan A. , Coplin William , Narayan Raj , Haines Stephen , Cruz-Flores Salvador , Zuccarello Mario , Brock David , Awad Issam , Ziai Wendy C. , Marmarou Anthony , Rhoney Denise , McBee Nichol , Lane Karen , Hanley Daniel F.
Published: August 2011

Background and Purpose—

Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis.

Methods—

Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups.

Results—

Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance;
P
=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution.

Conclusions—

Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.

Clinical Trial Registration—

Participant enrollment began before July 1, 2005.
Comprehensive Stroke Centers Overcome the Weekend Versus Weekday Gap in Stroke Treatment and Mortality
Authors: McKinney James S. , Deng Yingzi , Kasner Scott E. , Kostis John B. ,   for the Myocardial Infarction Data Acquisition System (MIDAS 15) Study Group
Published: August 2011

Background and Purpose—

Hospital staffing may be reduced on weekends. Prior studies of weekend disparities in stroke care have focused on in-hospital mortality with variable results. We hypothesized that 90-day mortality was higher in patients with stroke hospitalized on weekends versus weekdays, and this difference has been minimized over time by improvements in organization and delivery of stroke care.

Methods—

We used the Myocardial Infarction Data Acquisition System administrative database, which includes data on patients discharged with a primary diagnosis of cerebral infarction from all nonfederal acute care hospitals in New Jersey between 1996 and 2007. Out-of-hospital deaths were assessed by matching MIDAS records with New Jersey death registration files. New Jersey hospitals are designated by the state as comprehensive stroke centers, primary stroke centers, or nonstroke centers. The primary outcome measure was 90-day all-cause mortality after hospital admission.

Results—

A total of 134 441 patients were admitted with a primary diagnosis of cerebral infarction during the study period. A total of 23.4% were admitted to a comprehensive stroke center, 51.5% to a primary stroke center, and 25.1% to a nonstroke center. Ninety-day mortality was greater in patients with stroke admitted on weekends compared with weekdays (17.2% versus 16.5%;
P
=0.002). The adjusted risk of death at 90 days was significantly greater for weekend admission (hazard ratio, 1.05; 95% CI, 1.02 to 1.09). No difference in 90-day mortality was observed for patients admitted to comprehensive stroke centers on weekends versus weekdays (hazard ratio, 1.01; 95% CI, 0.95 to 1.08).

Conclusions—

Patients with stroke admitted on weekends to New Jersey hospitals had a significantly higher risk of death by 90 days. No such difference in mortality was observed at comprehensive stroke centers.
Acute Pediatric Stroke
Authors: Turney Colin M. , Wang Wei , Seiber Eric , Lo Warren
Published: August 2011

Background and Purpose—

Recent studies examined the overall cost of pediatric stroke, but there are little data regarding the sources of these costs. We examined an administrative database that collected charges from 24 US children's hospitals to determine the sources of costs for acute hospital care of stroke.

Methods—

We used International Classification of Diseases, 9th Revision codes to search the Pediatric Health Information System. From 2003 to 2009 there were 1667 patients who had a primary diagnosis of stroke, 703 of which were hemorrhagic and 964 were ischemic. Individual costs, excluding physician charges, were gathered under 7 categories that were ranked to determine which contributed the most to total cost. Individual costs were ranked within their categories. We analyzed costs based on stroke type. Total costs were adjusted using the US Consumer Price Index to compare increases with the rate of inflation.

Results—

Median total cost for any stroke was $19 548 (interquartile range, $10 764–$40 721). The category “other/nursing” contributed the most to hospital costs followed by imaging, laboratory, and pharmacy. Brain MRI and CT contributed the most to imaging costs. Hemorrhagic strokes (median $24 843) were more expensive than ischemic strokes (median $16 954). Total cost increased from 2003 to 2009, but no overall annual trend emerged after controlling for gender, age, race, and hospital.

Conclusions—

This is the first in-depth analysis of cost for pediatric stroke care. The highest cost categories are potential targets for cost containment but are also crucial for effective diagnosis and treatment. Necessary yet prudent use of imaging technologies and inpatient stays may be strategies for cost containment.
High-Intensity Signal on Time-of-Flight Magnetic Resonance Angiography Indicates Carotid Plaques at High Risk for Cerebral Embolism During Stenting
Authors: Yoshimura Shinichi , Yamada Kiyofumi , Kawasaki Masanori , Asano Takahiko , Kanematsu Masayuki , Takamatsu Manabu , Hara Akira , Iwama Toru
Published: August 2011

Background and Purpose—

A major disadvantage of carotid artery stenting (CAS) compared to carotid endarterectomy is the increased risk of cerebral embolism. Thus, establishing a simple method to discriminate fragile plaques on preoperative routine examination is important. The present study examined whether high-intensity signal (HIS) in the plaque on time-of-flight (TOF) MRA, performed for screening, can discriminate plaque at high risk for cerebral embolism during CAS.

Methods—

In the 30 patients treated using carotid endarterectomy, relationships between pathological findings of the plaques and TOF-MRA findings were analyzed. In the 112 patients treated using CAS, postoperative ipsilateral ischemic lesions on diffusion-weighted imaging and periprocedural ischemic symptoms were analyzed.

Results—

The percentage area of intraplaque hemorrhage stained by glycophorin A was significantly larger in HIS-positive plaques (51.8%±9.8%) than in HIS-negative plaques (8.6%±9.4%;
P
<0.001). Postoperative ischemic lesions on diffusion-weighted imaging were more frequent in the HIS-positive plaques (25/38; 65.8%) than in the HIS-negative plaques (26/74; 35.1%;
P
=0.002). Periprocedural ischemic symptoms were more frequently observed in HIS-positive plaques (7/38; 18.4%) than in HIS-negative plaques (1/74; 1.4%;
P
=0.003). Multivariate logistic regression analysis identified HIS on TOF-MRA as an independent predictor of periprocedural ischemic symptoms (odds ratio, 15.08; 95% confidence interval, 1.76–129.0).

Conclusions—

HIS in the plaque on TOF-MRA performed for screening could discriminate plaques at high risk for cerebral embolism during CAS.
Relations of Blood Inflammatory Marker Levels With Cerebral Microbleeds
Authors: Miwa Kaori , Tanaka Makiko , Okazaki Shuhei , Furukado Shigetaka , Sakaguchi Manabu , Kitagawa Kazuo
Published: August 2011

Background and Purpose—

Cerebral microbleeds (CMB) are observed in the elderly and have been regarded as one of the manifestations of small vessel disease. Although inflammatory processes have attracted much attention not only in large-artery disease, but also in small vessel disease, their involvement in CMB remains to be determined. The purpose of this study is to clarify relations between inflammatory marker levels and CMB.

Methods—

Four hundred thirty-one patients without histories of cerebrovascular diseases were prospectively enrolled. The presence and number of CMB were assessed on gradient-echo magnetic resonance imaging. As common inflammatory markers, serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-18 (IL-18) were evaluated.

Results—

CMB were found in 65 patients (15%). In 35 patients, at least one CMB was found in deep locations, but 30 patients had strictly lobar CMB. Levels of hsCRP, IL-6, and IL-18 were higher in patients with CMB than in those without. Logistic regression analyses showed that each 1SD increase in each inflammatory marker level was significantly associated with the presence of CMB after adjustment for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction, and white matter hyperintensity. The OR (95% CI) of hsCRP, IL-6, and IL-18 was 1.81 (1.35–2.46), 1.73 (1.18–2.61), and 2.41 (1.44–4.52), respectively. Furthermore, the inflammatory marker levels were associated with both deep and lobar CMB.

Conclusions—

Higher levels of hsCRP, IL-6, and IL-18 are associated with CMB, in both deep and lobar locations, suggesting the involvement of inflammation in CMB.
Replication Study of Chr17q25 With Cerebral White Matter Lesion Volume
Authors: Verhaaren Benjamin F.J. , de Boer Renske , Vernooij Meike W. , Rivadeneira Fernando , Uitterlinden André G. , Hofman Albert , Krestin Gabriel P. , van der Lugt Aad , Niessen Wiro J. , Breteler Monique M.B. , Ikram M. Arfan
Published: August 2011

Background and Purpose—

Recently, the first genomewide association study on cerebral white matter lesion burden identified chr17q25 to be significantly associated with white matter lesions. We report on the first independent replication study of this genetic association.

Methods—

In a population-based cohort study, we investigated the association between the 6 genomewide significant single nucleotide polymorphisms at that locus and cerebral white matter lesion volume on MRI, measured quantitatively, adjusted for age, sex, and intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk factors were evaluated separately. Finally, we performed a meta-analysis of all published data for the single most significant single nucleotide polymorphism, rs3744028.

Results—

The risk alleles of all the 6 single nucleotide polymorphisms were significantly associated with white matter lesion volume with
P
=1.1*10
−3
for rs3744028, adjusted for age, sex, and intracranial volume. Additional adjustments only had minor influence on these associations. A meta-analysis with all published data for rs3744028 resulted in a probability value of 5.3*10
−17
.

Conclusions—

This study further establishes chr17q25 as a novel genetic locus for WML volume.
Increased Frequency of First-Episode Poststroke Depression After Discontinuation of Escitalopram
Authors: Mikami Katsunaka , Jorge Ricardo E. , Moser David J. , Arndt Stephan , Jang Mijin , Solodkin Ana , Small Steven L. , Fonzetti Pasquale , Hegel Mark T. , Robinson Robert G.
Published: August 2011

Background and Purpose—

The purpose of this study was to compare escitalopram, problem-solving therapy, and placebo to prevent poststroke depression during 6 months after discontinuation of treatment.

Methods—

We examined for depression 33 patients assigned to placebo, 34 to escitalopram, and 41 to problem-solving therapy.

Results—

After controlling for age, gender, prior mood disorder, and severity of stroke, new-onset major depression and Hamilton Depression scores were significantly higher 6 months after escitalopram was discontinued compared with the problem-solving therapy or placebo groups.

Conclusions—

Discontinuation of escitalopram may increase poststroke depressive symptoms.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00071643.
Time Scales of Terrestrial Carbon Response Related to Land-Use Application: Implications for Initializing an Earth System Model
Authors: Sentman Lori T. , Shevliakova Elena , Stouffer Ronald J. , Malyshev Sergey
Published: August 2011

The dynamic vegetation and carbon cycling component, LM3V, of the Geophysical Fluid Dynamics Laboratory (GFDL) prototype Earth system model (ESM2.1), has been designed to simulate the effects of land use on terrestrial carbon pools, including secondary vegetation regrowth. Because of the long time scales associated with the carbon adjustment, special consideration is required when initializing the ESM when historical simulations are conducted. Starting from an equilibrated, preindustrial climate and potential vegetation state in an offline land-only model (LM3V), estimates of historical land use are instantaneously applied in five experiments beginning in the following calendar years: 1500, 1600, 1700, 1750, and 1800. This application results in the land carbon pools experiencing an abrupt change—a carbon shock—and the secondary vegetation needs time to regrow into consistency with the harvesting history. The authors find that it takes approximately 100 years for the vegetation to recover from the carbon shock, whereas soils take at least 150 years to recover. The vegetation carbon response is driven primarily by land-use history, whereas the soil carbon response is affected by both land-use history and the geographic pattern of soil respiration rates. Based on these results, the authors recommend the application of historical land-use scenarios in 1700 to provide sufficient time for the land carbon in ESMs with secondary vegetation to equilibrate to adequately simulate carbon stores at the start of the historical integrations (i.e., 1860) in a computationally efficient manner.
Determining Vertical Water Velocities from Seaglider
Authors: Frajka-Williams Eleanor , Eriksen Charles C. , Rhines Peter B. , Harcourt Ramsey R.
Published: August 2011

Vertical velocities in the world’s oceans are typically small, less than 1 cm s−1, posing a significant challenge for observational techniques. Seaglider, an autonomous profiling instrument, can be used to estimate vertical water velocity in the ocean. Using a Seaglider’s flight model and pressure observations, vertical water velocities are estimated along glider trajectories in the Labrador Sea before, during, and after deep convection. Results indicate that vertical velocities in the stratified ocean agree with the theoretical Wentzel–Kramers–Brillouin (WKB) scaling of w; and in the turbulent mixed layer, scale with buoyancy, and wind forcing. It is estimated that accuracy is to within 0.5 cm s−1. Because of uncertainties in the flight model, velocities are poor near the surface and deep apogees, and during extended roll maneuvers. Some of this may be improved by using a dynamic flight model permitting acceleration and by better constraining flight parameters through pilot choices during the mission.
Exploring Variations in People’s Sources, Uses, and Perceptions of Weather Forecasts
Authors: Demuth Julie L. , Lazo Jeffrey K. , Morss Rebecca E.
Published: August 2011

Past research has shown that individuals vary in their attitudes and behaviors regarding weather forecast information. To deepen knowledge about these variations, this article explores 1) patterns in people’s sources, uses, and perceptions of everyday weather forecasts; and 2) relationships among people’s sources, uses, and perceptions of forecasts, their personal characteristics, and their experiences with weather and weather forecasts. It does so by performing factor and regression analysis on data from a nationwide survey of the U.S. public, combined with other data. Forecast uses factored into planning for leisure activities and for work/school-related activities, while knowing what the weather will be like and planning how to dress remained separate. Forecast parameters factored into importance of precipitation parameters and of temperature-related parameters, suggesting that these represent conceptually different constructs. Regression analysis showed that the primary drivers for how often people obtain forecasts are what they use forecasts for and their perceived importance of and confidence in forecast information. People’s forecast uses are explained in large part by their frequency of obtaining forecasts and their perceived importance of temperature-related and precipitation forecast information. This suggests that that individuals’ frequency of obtaining forecasts, forecast use, and importance of forecast parameters are closely interrelated. Sociodemographic characteristics and, to a lesser extent, weather-related experience also influence some aspects of people’s forecast sources, uses, and perceptions. These findings continue to build understanding of variations among weather forecast users, which can help weather information providers improve communication of forecasts to better meet users’ needs.
An Increase in the Number of Tornado Reports in Brazil
Authors: Silva Dias Maria A. F.
Published: August 2011

This paper presents the development of tornado reports in Brazil since the middle of the twentieth century, both for the country as a whole and for the five regions of Brazil: the south, southeast, central-west, northeast, and north. No official tornado registry exists in Brazil so the reports come from various sources. Most of the tornadoes reported are from the south and southeast regions. The low number of reports for the central-west regions suggests, in view of the literature on intense storms and mesoscale convective complexes, that most tornadoes cases go unreported. The increase in tornado reports is compared to the evolution of population density and communications, with the latter represented by the evolution of local television stations and the popularization of the Internet. One particular event is a new Web site for volunteer tornado reports, which has completely changed the trends of tornado reports. Another possible cause for an increase in the number of tornado reports in the south and southern regions could be a shift in climate variability in this region in the 1970s, which has been reported by several authors. However, the increase in rainfall and extreme events reported by these studies point to an increase of as much as 40%, which is not compatible with the observed tenfold increase in tornado reports.
Modeling the Spatial Distribution of Snow Cover in the Dudhkoshi Region of the Nepal Himalayas
Authors: Shrestha Maheswor , Wang Lei , Koike Toshio , Xue Yongkang , Hirabayashi Yukiko
Published: August 2011

In this study, a distributed biosphere hydrological model with three-layer energy-balance snow physics [an improved version of the Water and Energy Budget–based Distributed Hydrological Model (WEB-DHM-S)] is applied to the Dudhkoshi region of the eastern Nepal Himalayas to estimate the spatial distribution of snow cover. Simulations are performed at hourly time steps and 1-km spatial resolution for the 2002/03 snow season during the Coordinated Enhanced Observing Period (CEOP) third Enhanced Observing Period (EOP-3). Point evaluations (snow depth and upward short- and longwave radiation) at Pyramid (a station of the CEOP Himalayan reference site) confirm the vertical-process representations of WEB-DHM-S in this region. The simulated spatial distribution of snow cover is evaluated with the Moderate Resolution Imaging Spectroradiometer (MODIS) 8-day maximum snow-cover extent (MOD10A2), demonstrating the model’s capability to accurately capture the spatiotemporal variations in snow cover across the study area. The qualitative pixel-to-pixel comparisons for the snow-free and snow-covered grids reveal that the simulations agree well with the MODIS data to an accuracy of 90%. Simulated nighttime land surface temperatures (LST) are comparable to the MODIS LST (MOD11A2) with mean absolute error of 2.42°C and mean relative error of 0.77°C during the study period. The effects of uncertainty in air temperature lapse rate, initial snow depth, and snow albedo on the snow-cover area (SCA) and LST simulations are determined through sensitivity runs. In addition, it is found that ignoring the spatial variability of remotely sensed cloud coverage greatly increases bias in the LST and SCA simulations. To the authors’ knowledge, this work is the first to adopt a distributed hydrological model with a physically based multilayer snow module to estimate the spatial distribution of snow cover in the Himalayan region.
Pediatric Autonomic Testing
Authors: Sukul Devraj , Chelimsky Thomas C. , Chelimsky Gisela
Published: August 2011

Objective. To describe the reasons for referral, autonomic diagnoses, test results, and patient management in a large pediatric population referred for testing for an autonomic disorder. Design. The authors reviewed autonomic testing data and medical records for patients aged 18 years and younger who underwent testing between 1993 and 2007 and who had adequate clinical data. Relevance of test results to clinical symptoms was ranked on a 3-point scale. Treatments were noted and their benefit ranked on a 5-point scale. Results. Among 142 pediatric patients identified, postural tachycardia syndrome was most common (71%) while orthostatic hypotension was rare (5%). Testing provided relevant information regarding the patient’s symptoms in 88% of the cases. Beta-blockers were the most commonly prescribed medication (59%); 73% improved. Conclusions. Postural tachycardia syndrome was common in this large pediatric population, whereas orthostatic hypotension was infrequent. The symptomatic improvement in the majority bears an unclear relationship to treatment. Prospective studies are needed.
Parent Medication Concerns Predict Underutilization of Mental Health Services for Minority Children With ADHD
Authors: Berger-Jenkins Evelyn , McKay Mary , Newcorn Jeffrey , Bannon William , Laraque Danielle
Published: August 2011

Objective. Disparities in attention deficit hyperactivity disorder (ADHD) treatment are recognized with minority children using services less than nonminority children. The authors examine minority parents’ knowledge and perceptions of ADHD as they relate to service utilization. Methods. Using a longitudinal cohort design, parents of children with untreated ADHD were surveyed regarding their knowledge and perceptions of ADHD and then followed for 3 to 6 months to determine whether they used services. Results. Seventy parents of 5- to 18-year-old children with untreated ADHD were enrolled. Of the 70 children, 33 (47.1%) had not attended any mental health appointments and 51 (72.9%) had not used any treatments by 3- to 6-month follow-up. Logistic regression indicated that increasing age and medication concerns were associated with less follow-up at mental health appointments ( P < .05) and less utilization of treatments ( P < .05). Conclusions. The results of this study highlight the importance of addressing medication concerns, when referring minority children to mental health services or offering treatments.
Piloting Group Well Child Visits in Pediatric Resident Continuity Clinic
Authors: Saysana Michele , Downs Stephen M.
Published: August 2011

Introduction. Well child care is taught with individual visits in pediatric residency. Teaching residents how to deliver well child care efficiently is critical. Group well child care brings multiple families together for visits. The authors piloted group visits in pediatric residency clinic. Methods. The authors conducted group visits for 1- to 12-month old children. Seven families completed the group visits and were surveyed. Nine residents (intervention group) conducted group visits. Eighteen months after implementation, the intervention and control groups in the same clinic surveyed. Results. All families recommended group visits. The intervention group residents reported significantly more direct observations ( P < .05). Trends toward improvement of teaching and role modeling for the intervention group were also observed. Discussion. The authors’ continuity clinic had success implementing group visits, and families were recommended the visits. Group visits offer a natural environment to observe residents while exposing them to another way to deliver well child care.
Evaluation of the Precision of Emergency Department Diagnoses in Young Children With Fever
Authors: Colvin Joshua M. , Jaffe David M. , Muenzer Jared T.
Published: August 2011

Objective. To characterize causes of fever in children presenting to a pediatric emergency department (ED). Methods. One-year retrospective review of ED records. Inclusion criteria were 2 to 36 months of age with a documented temperature ≥39°C. Exclusion criteria were elopement, repeat visit, and underlying diagnosis with a predisposition to infection. Medical records were reviewed using a predefined, study-specific, data abstraction tool. Based on diagnosis and pathogen detection, visits were assigned to 3 groups, laboratory confirmed pathogen and focal or nonfocal diagnosis without confirmed pathogen. Results. A total of 1091 visits met inclusion criteria. Fourteen percent had a pathogen detected, 56% had a focal diagnosis without a confirmed pathogen, and 30% had a nonfocal diagnosis without confirmed pathogen. Conclusions. In a cohort of febrile children 2 to 36 months of age, only 14% had a confirmed pathogen. New rapid viral diagnostic techniques may provide an opportunity to improve diagnostic certainty in young children presenting with fever.
Comparison of Reliability Measures Under Factor Analysis and Item Response Theory
Authors: Cheng Ying , Yuan Ke-Hai , Liu Cheng
Published: August 2011

Reliability of test scores is one of the most pervasive psychometric concepts in measurement. Reliability coefficients based on a unifactor model for continuous indicators include maximal reliability ρ and an unweighted sum score–based ω, among many others. With increasing popularity of item response theory, a parallel reliability measure π has been introduced using the information function. This article studies the relationship among the three reliability coefficients. Exploiting the equivalency between item factor analysis and the normal ogive model, π(2) for dichotomous data is shown to be always smaller than ρ. Additional results imply that ω is typically greater than π(2) in practical conditions, though mathematically there is no dominant relationship between π(2) and ω. Furtherresults indicate that, as the number of response categories increases, π can surpass ω. The reasons why π and ω fall short of ρ are also explored from an information gain/loss perspective. Implications of the findings on scale development and analysis are discussed.
Characterizing Sources of Uncertainty in Item Response Theory Scale Scores
Authors: Yang Ji Seung , Hansen Mark , Cai Li
Published: August 2011

Traditional estimators of item response theory scale scores ignore uncertainty carried over from the item calibration process, which can lead to incorrect estimates of the standard errors of measurement (SEMs). Here, the authors review a variety of approaches that have been applied to this problem and compare them on the basis of their statistical methods and goals. They then elaborate on the particular flexibility and usefulness of a multiple imputation–based approach, which can be easily applied to tests with mixed item types and multiple underlying dimensions. This proposed method obtains corrected estimates of individual scale scores, as well as their SEMs. Furthermore, this approach enables a more complete characterization of the impact of parameter uncertainty by generating confidence envelopes (intervals) for item trace lines, test information functions, conditional SEM curves, and the marginal reliability coefficient. The multiple imputation–based approach is illustrated through the analysis of an artificial data set, then applied to data from a large educational assessment. A simulation study was also conducted to examine the relative contribution of item parameter uncertainty to the variability in score estimates under various conditions. The authors found that the impact of item parameter uncertainty is generally quite small, though there are some conditions under which the uncertainty carried over from item calibration contributes substantially to variability in the scores. This may be the case when the calibration sample is small relative to the number of item parameters to be estimated or when the item response theory model fit to the data is multidimensional.
A Robust Outlier Approach to Prevent Type I Error Inflation in Differential Item Functioning
Authors: Magis David , De Boeck Paul
Published: August 2011

The identification of differential item functioning (DIF) is often performed by means of statistical approaches that consider the raw scores as proxies for the ability trait level. One of the most popular approaches, the Mantel–Haenszel (MH) method, belongs to this category. However, replacing the ability level by the simple raw score is a source of potential Type I error inflation, not only in the presence of DIF but also when DIF is absent and in the presence of impact. The purpose of this article is to present an alternative statistical inference approach based on the same measure of DIF but such that the Type I error inflation is prevented. The key notion is that for DIF items, the measure has an outlying value that can be identified as such with inference tools from robust statistics. Although we use the MH log odds ratio as a statistic, the inference is different. A simulation study is performed to compare the robust statistical inference with the classical inference method, both based on the MH statistic. As expected, the Type I error rate inflation is avoided with the robust approach, although the power of the two methods is similar.
Ecumenical Learning in Theological Education: The World Council of Churches Perspective
Authors: Werner Dietrich
Published: August 2011

The article highlights historical and programatic aspects of the Programme on Ecumenical Theological Education of the World Council of Churches. Special importance is gven to new insights and challenges which were identified during the Edinburgh 2010 centenary conference. Key convictions which underline the urgency of more international cooperation in the tasks to promote faculty development and capacity development in theological education of the churches of the South are spelled out as well as some crucial tasks for common solidarity between churches, mission agencies and theological colleges worldwide. A number of new key resources and publications on issues of theological education in World Christianity are identified.
Readings from the Road: Contextual Bible Study with a Group of Homeless and Vulnerably-Housed People
Authors: Cornwall Susannah , Nixon David
Published: August 2011

Readings from the Road, a British Academy-funded small research project, investigated the use of Contextual Bible Study (CBS) with a group of homeless and vulnerably-housed people at a soup kitchen in South-West England. The transient nature of the homeless community presented particular challenges in using this method, but the non-directive and democratic nature of CBS proved valuable. The authors discuss three themes arising from the study sessions: home and place, judgment and stigmatization, and the figure of Jesus. Participants’ linking of biblical themes with their own experiences and broader social events are explored. The authors note that consciously privileging the experience and knowledge of those whose narratives or reading sites are silenced or devalued by mainstream religious traditions is not unequivocally positive, but that the homeless participants’ liminal, insider-outsider relationship to the rest of society is a significant factor in their ability to query and subvert established discourses, providing flashes of imagery which might be deemed prophetic.
Revalorized Black Embodiment
Authors: Hall Joshua M.
Published: August 2011

This article explores Fanon’s thought on dance, beginning with his explicit treatment of it in Black Skin, White Masks and The Wretched of the Earth. It then broadens to consider his theorization of Black embodiment in racist and colonized societies, considering how these analyses can be reformulated as a phenomenology of dance. This will suggest possibilities for fruitful encounters between the two domains in which (a) dance can be valorized while (b) opening up sites of resignification and resistance for Black persons and communities—including a revalorization of Black embodiment as a kind of empowering danced experience.
Memories in Photography and Rebirth
Authors: Ukpokolo Isaac E.
Published: August 2011

The aim of this article is to show that beyond the need for the justification of the belief in reincarnation, beyond the quest for evidences to prove its reality or otherwise, the idea of rebirth has a pragmatic role in the cultures where it is held. Using the theorization of rebirth among the Esan people of southern Nigeria as a pilot, it asserts that the idea of rebirth plays a psychosocial, therapeutic function of comfort and healing for those traumatized by the death of a loved one. This, it shall be seen, is similar to, even more reliable than, the role of photography in preserving cherished memories. The article does not, therefore, mean to join issues in the myth-reality or truth-falsehood debate on rebirth among scholars but attempts to establish the role of reincarnation, like photography, in bringing the past into the present.