bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderately Decreased Cholesterol Absorption Rates Are Associated With a Large Atheroprotective Effect
Authors: Greenberg Michael E. , Smith Jonathan D. , Sehayek Ephraim
Published: August 2009

Objective—

Human treatment with ezetimibe results in a moderate 50% to 54% decrease in cholesterol absorption and a 15% to 20% decrease in plasma LDL-cholesterol levels; nevertheless, the efficacy of ezetimibe therapy has been recently challenged by the ENHANCE trial. We examined the efficacy of a moderate decrease in cholesterol absorption in preventing atherosclerosis formation in the mouse.

Methods and Results—

Congenic 14DKK animals, consisting of a castaneus (CASA/Rk) chromosome 14 interval introgressed onto the C57BL/6J background, displayed a moderate decrease in cholesterol absorption rates. The effect of moderately decreased absorption on atherosclerosis formation was determined in 14DKK apolipoprotein E knockouts (14DKK-apoEKO). When compared to chow diet–fed control apoEKO mice, congenic 14DKK-apoEKO displayed a moderate 41% decrease in cholesterol absorption rates, 30% to 37% decrease in plasma cholesterol levels, and a 70% decrease in atherosclerosis formation. Studies on cholesterol efflux and reverse cholesterol transport (RCT) from 14DKK bone marrow–derived macrophages rejected a 14DKK interval-dependent atheroprotective effects that operate in macrophages. In contrast, 14DKK-apoEKO congenics were characterized by a 60% increase in RCT from peripheral tissue macrophages.

Conclusions—

These studies strongly suggest that moderately decreased cholesterol absorption rates result in a large atheroprotective effect attributable to a decrease in plasma cholesterol levels and an increase in RCT from peripheral tissue macrophages.
VEGF and RANKL Regulation of NFATc1 in Heart Valve Development
Authors: Combs Michelle D. , Yutzey Katherine E.
Published: August 2009

Rationale:

NFATc1 (nuclear factor of activated T-cells cytoplasmic 1) activity in endocardial cushion (ECC) endothelial cells is required for normal ECC growth and extracellular matrix (ECM) remodeling during heart valve development.

Objective:

The mechanisms of NFATc1 activation and downstream effects on cell proliferation and ECM-remodeling enzyme gene expression were examined in
NFATc1
mutant mice and chick ECC explants.

Methods and Results:

NFATc1
−/−

mice display reduced proliferation of ECC endothelial and mesenchymal cells at embryonic day 10.5, whereas myocardial cells are unaffected. Vascular endothelial growth factor A (VEGF) activates NFATc1 and promotes ECC cell proliferation via the regulatory phosphatase, calcineurin, and mitogen-activated protein kinase–extracellular signal-regulated kinase 1–extracellular signal-regulated kinase 1/2 (MEK1-ERK1/2)–dependent signaling. As ECCs mature, RANKL (receptor activator of nuclear factor κB ligand) and the ECM-remodeling enzyme cathepsin K (CtsK) are expressed by ECC endothelial cells. RANKL inhibits VEGF-induced cell proliferation while causing increased expression of
CtsK
via calcineurin/NFATc1 and c-Jun N-terminal kinase (JNK)1/2-dependent signaling.

Conclusion:

These data support a novel mechanism for the transition from ECC growth to remodeling in which NFATc1 promotes a sequential pattern of gene expression via cooperation with ligand-specific cofactors such as MEK1-ERK1/2 or JNK1/2.
Using Lidocaine and Benzocaine to Link Sodium Channel Molecular Conformations to State-Dependent Antiarrhythmic Drug Affinity
Authors: Hanck Dorothy A. , Nikitina Elena , McNulty Megan M. , Fozzard Harry A. , Lipkind Gregory M. , Sheets Michael F.
Published: August 2009

Rationale:Lidocaine and other antiarrhythmic drugs bind in the inner pore of voltage-gated Na channels and affect gating use-dependently. A phenylalanine in domain IV, S6 (Phe1759 in NaV1.5), modeled to face the inner pore just below the selectivity filter, is critical in use-dependent drug block.

Objective:Measurement of gating currents and concentration-dependent availability curves to determine the role of Phe1759 in coupling of drug binding to the gating changes.

Methods and Results:The measurements showed that replacement of Phe1759 with a nonaromatic residue permits clear separation of action of lidocaine and benzocaine into 2 components that can be related to channel conformations. One component represents the drug acting as a voltage-independent, low-affinity blocker of closed channels (designated as lipophilic block), and the second represents high-affinity, voltage-dependent block of open/inactivated channels linked to stabilization of the S4s in domains III and IV (designated as voltage-sensor inhibition) by Phe1759. A homology model for how lidocaine and benzocaine bind in the closed and open/inactivated channel conformation is proposed.

Conclusions:These 2 components, lipophilic block and voltage-sensor inhibition, can explain the differences in estimates between tonic and open-state/inactivated-state affinities, and they identify how differences in affinity for the 2 binding conformations can control use-dependence, the hallmark of successful antiarrhythmic drugs.
Regular Feeding Plays an Important Role in Cholesterol Homeostasis Through the Liver Circadian Clock
Authors: Yamajuku Daisuke , Okubo Shingo , Haruma Tomonori , Inagaki Takahiko , Okuda Yuji , Kojima Tomoko , Noutomi Keiji , Hashimoto Seiichi , Oda Hiroaki
Published: August 2009

Rationale:

Peripheral clock control and the relevance of the circadian rhythm to physiology and disease are major questions in mammalian circadian biology.

Objective:

We examined the physiological functions of the liver clock.

Methods and Results:

We established a suppressed feeding schedule regimen constituting a high-cholesterol diet delivered every 6 hours without changes in energy and cholesterol intake. We found that rats exposed to this regimen developed hypercholesteremia. In the liver, the rhythmicity of expression of several clock genes was disrupted. Furthermore, the nocturnal expression of the CYP7A1 gene, which encodes the rate-limiting enzyme for the conversion of cholesterol to bile acids, was shifted to a diurnal pattern. Indeed, suppression of a regular feeding rhythm increased the secretion rate of very-low-density lipoprotein cholesterol from the liver and decreased the excretion of fecal bile acids.

Conclusions:

Our results demonstrated that not only the amount and quality of food but also the timing of meals has crucial health implications.
Loss of Plakophilin-2 Expression Leads to Decreased Sodium Current and Slower Conduction Velocity in Cultured Cardiac Myocytes
Authors: Sato Priscila Y. , Musa Hassan , Coombs Wanda , Guerrero-Serna Guadalupe , Patiño Gustavo A. , Taffet Steven M. , Isom Lori L. , Delmar Mario
Published: August 2009

Rationale:

Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na
V
1.5) to this region.

Objective:

To establish the association of PKP2 with sodium channels and its role on action potential propagation.

Methods and Results:

Biochemical, patch clamp, and optical mapping experiments demonstrate that PKP2 associates with Na
V
1.5, and that knockdown of PKP2 expression alters the properties of the sodium current, and the velocity of action potential propagation in cultured cardiomyocytes.

Conclusions:

These results emphasize the importance of intermolecular interactions between proteins relevant to mechanical junctions, and those involved in electric synchrony. Possible relevance to the pathogenesis of arrhythmogenic right ventricular cardiomyopathy is discussed.
Nicotinamide Phosphoribosyltransferase Regulates Cell Survival Through NAD
+
Synthesis in Cardiac Myocytes
Authors: Hsu Chiao-Po , Oka Shinichi , Shao Dan , Hariharan Nirmala , Sadoshima Junichi
Published: August 2009

Rationale
:

NAD
+
acts not only as a cofactor for cellular respiration but also as a substrate for NAD
+
-dependent enzymes, such as Sirt1. The cellular NAD
+
synthesis is regulated by both the de novo and the salvage pathways. Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the salvage pathway.

Objective
:

Here we investigated the role of Nampt in mediating NAD
+
synthesis in cardiac myocytes and the function of Nampt in the heart in vivo.

Methods and Results
:

Expression of Nampt in the heart was significantly decreased by ischemia, ischemia/reperfusion and pressure overload. Upregulation of Nampt significantly increased NAD
+
and ATP concentrations, whereas downregulation of Nampt significantly decreased them. Downregulation of Nampt increased caspase 3 cleavage, cytochrome
c
release, and TUNEL-positive cells, which were inhibited in the presence of Bcl-xL, but did not increase hairpin 2–positive cells, suggesting that endogenous Nampt negatively regulates apoptosis but not necrosis. Downregulation of Nampt also impaired autophagic flux, suggesting that endogenous Nampt positively regulates autophagy. Cardiac-specific overexpression of Nampt in transgenic mice increased NAD
+
content in the heart, prevented downregulation of Nampt, and reduced the size of myocardial infarction and apoptosis in response to prolonged ischemia and ischemia/reperfusion.

Conclusions
:

Nampt critically regulates NAD
+
and ATP contents, thereby playing an essential role in mediating cell survival by inhibiting apoptosis and stimulating autophagic flux in cardiac myocytes. Preventing downregulation of Nampt inhibits myocardial injury in response to myocardial ischemia and reperfusion. These results suggest that Nampt is an essential gatekeeper of energy status and survival in cardiac myocytes.
Chronic Endoplasmic Reticulum Stress Activates Unfolded Protein Response in Arterial Endothelium in Regions of Susceptibility to Atherosclerosis
Authors: Civelek Mete , Manduchi Elisabetta , Riley Rebecca J. , Stoeckert Christian J. , Davies Peter F.
Published: August 2009

Rationale
:

Endothelial function and dysfunction are central to the focal origin and regional development of atherosclerosis; however, an in vivo endothelial phenotypic footprint of susceptibility to atherosclerosis preceding pathological change remains elusive.

Objective
:

To conduct a comparative multi-site genomics study of arterial endothelial phenotype in atherosusceptible and atheroprotected regions.

Methods and Results
:

Transcript profiles of freshly isolated endothelial cells from 7 discrete arterial regions in normal swine were analyzed to determine the steady state in vivo endothelial phenotypes in regions of varying susceptibilities to atherosclerosis. The most abundant common feature of the endothelium of all atherosusceptible regions was the upregulation of genes associated with endoplasmic reticulum (ER) stress. The unfolded protein response pathway, induced by ER stress, was therefore investigated in detail in endothelium of the atherosusceptible aortic arch and was found to be partially activated. ER transmembrane signal transducers IRE1α and ATF6α and their downstream effectors, but not PERK, were activated concomitant with a higher transcript expression of protein folding enzymes and chaperones, indicative of ER stress in vivo.

Conclusions
:

The findings demonstrate the prevalence of chronic endothelial ER stress and activated unfolded protein response in vivo at atherosusceptible arterial sites. We propose that chronic localized biological stress is linked to spatial susceptibility of the endothelium to the initiation of atherosclerosis.
Basal Ganglionic Infarction Before Mechanical Thrombectomy Predicts Poor Outcome
Authors: Loh Yince , Towfighi Amytis , Liebeskind David S. , MacArthur David L. , Vespa Paul , Gonzalez Nestor R. , Tateshima Satoshi , Starkman Sidney , Saver Jeffrey L. , Shi Zhong-Song , Jahan Reza , Viñuela Fernando , Duckwiler Gary R.
Published: August 2009

Background and Purpose—

Use of mechanical thrombectomy for acute cerebrovascular occlusions is increasing. Preintervention MRI patterns may be helpful in predicting prognosis.

Methods—

We reviewed all Merci thrombectomy cases of either terminal ICA or M1 occlusions and classified them according to diffusion MRI patterns of (1) completed basal ganglia infarct (pure M1a), (2) near-completed basal ganglia infarct (incomplete M1a), and (3) relative sparing of deep MCA field (M1b). We compared the M1a and M1b patients with respect to neurological deficit on presentation, recanalization rates, hospital length of stay, and disability on discharge. We also determined whether deep MCA compromise predicted hematomal hemorrhagic transformation (HT) and whether this correlated with worse clinical outcome at discharge.

Results—

The M1a group had worse pre-Merci NIHSS (21 versus 14,
P
=0.004), worse discharge NIHSS (12 versus 4,
P
<0.001), longer hospital length of stay (11.5 versus 6.4 days,
P
=0.003), and higher rates of discharge mRS ≥3 (OR 8.4, 95% CI 2.1 to 44.7) despite equivalent recanalization rates when compared to the M1b group. The M1a group had a higher rate of parenchymal hematomal HT (OR 6.7, 95% CI 1.02 to 183.3). Patients with such hematomal HT had higher rates of death or dependency discharge (100% versus 60%, OR=infinite).

Conclusions—

Among patients with ICA and M1 occlusions, preintervention diffusion MRI evidence of advanced injury in the basal ganglia bodes worse dysfunction and disability at discharge, longer hospital stays, and higher rates of hemorrhage after intervention when compared to other diffusion patterns.
Risk of Hip/Femur Fracture After Stroke
Authors: Pouwels Sander , Lalmohamed Arief , Leufkens Bert , de Boer Anthonius , Cooper Cyrus , van Staa Tjeerd , de Vries Frank
Published: August 2009

Background and Purpose—

Stroke increases the risk of hip/femur fracture, as seen in several studies, although the time course of this increased risk remains unclear. Therefore, our purpose is to evaluate this risk and investigate the time course of any elevated risk.

Methods—

We conducted a case-control study using the Dutch PHARMO Record Linkage System database. Cases (n=6763) were patients with a first hip/femur fracture; controls were matched by age, sex, and region. Odds ratio (OR) for the risk of hip/femur fracture was derived using conditional logistic regression analysis, adjusted for disease and drug history.

Results—

An increased risk of hip/femur fracture was observed in patients who experienced a stroke at any time before the index date (adjusted OR, 1.96; 95% CI, 1.65–2.33). The fracture risk was highest among patients who sustained a stroke within 3 months before the index date (adjusted OR, 3.35; 95% CI, 1.87–5.97) and among female patients (adjusted OR, 2.12; 95% CI, 1.73–2.59). The risk further increased among patients younger than 71 years (adjusted OR, 5.12; 95% CI, 3.00–8.75). Patients who had experienced a hemorrhagic stroke tended to be at a higher hip/femur fracture risk compared with those who had experienced an ischemic stroke.

Conclusions—

Stroke is associated with a 2.0-fold increase in the risk of hip/femur fracture. The risk was highest among patients younger than 71 years, females, and those whose stroke was more recent. Fall prevention programs, bone mineral density measurements, and use of bisphosphonates may be necessary to reduce the occurrence of hip/femur fractures during and after stroke rehabilitation.
Self- and Proxy-Report Agreement on the Stroke Impact Scale
Authors: Carod-Artal Francisco Javier , Coral Luciane Ferreira , Trizotto Daniele Stieven , Moreira Clarissa Menezes
Published: August 2009

Background and Purpose—

The purpose of this study was to examine proxy-patient agreement on the domains of the Stroke Impact Scale (SIS), as per the proxy-proxy perspective.

Methods—

Stroke patients were prospectively assessed by means of the NIH Stroke Scale, Barthel index, and modified Rankin scale. Proxies and patients answered the Hospital Anxiety and Depression Scale and the SIS 3.0. Comparisons of patient-proxy mean scores (paired
t
test), effect size, and intraclass correlation coefficients (ICC) were calculated for each of the SIS domains, and weighted kappa for individual items.

Results—

180 proxy-patient pairs were assessed. Proxies were younger (mean age: 43.1 versus 57.9 years) and had a higher education level (
P
<0.0001). The bias between patient-proxy mean differences was low (from 5.3, Strength, to 0.1, Communication). Proxies significantly scored patients as more severally affected in Strength (41.7 versus 36.6;
P
<0.0001) and ADL (46.2 versus 43.1;
P
=0.01) domains, and Composite Physical Domain (CPD; 39.7 versus 34.9;
P
<0.0001). The magnitude of difference was small (size effect: 0.21). ICC values for the SIS domains ranged from 0.17 (Emotion) to 0.79 (Hand function). The ICC value for the CPD was 0.83. Memory, Communication, Emotion, and Social Participation domains had ICC lower values. The weighted kappa values for the SIS items ranged from 0.09 (item 4e) to 0.80 (item 7d). Highest values (moderate/high agreement) were observed for the SIS-16 and CPD (kappa values: 0.31 to 0.80).

Conclusions—

Agreement between stroke patients and proxies was acceptable for most SIS domains and SIS-16. Proxy’s assessment of SIS subjective domains should be taken with caution.
Brain Microbleeds Relate to Higher Ambulatory Blood Pressure Levels in First-Ever Lacunar Stroke Patients
Authors: Staals Julie , van Oostenbrugge Robert J. , Knottnerus Iris L.H. , Rouhl Rob P.W. , Henskens Léon H.G. , Lodder Jan
Published: August 2009

Background and Purpose—

Hypertension is an important risk factor for brain microbleeds (BMBs) in lacunar stroke patients. However, beyond the qualitative label “hypertension,” little is known about the association with ambulatory blood pressure (BP) levels.

Methods—

In 123 first-ever lacunar stroke patients we performed 24-hour ambulatory BP monitoring after the acute stroke-phase. We counted BMBs on T2*-weighted gradient-echo MR images. Because a different etiology for BMBs according to location has been suggested, we distinguished between BMBs in deep and lobar location.

Results—

BMBs were seen in 36 (29.3%) patients. After adjusting for age, sex, number of antihypertensive drugs, asymptomatic lacunar infarcts, and white matter lesions, we found 24-hour, day, and night systolic and diastolic BP levels to be significantly associated with the presence and number of BMBs (odds ratios 1.6 to 2.3 per standard deviation increase in BP). Distinguishing between different locations, various BP characteristics were significantly associated with the presence of deep (or combined deep and lobar) BMBs, but not with purely lobar BMBs.

Conclusions—

Our results underline the role of a high 24-hour BP load as an important risk factor for BMBs. The association of BP levels with deep but not purely lobar BMBs is in line with the idea that different vasculopathies might be involved. Deep BMBs may be a particular marker of BP-related small vessel disease, but longitudinal and larger studies are now warranted to substantiate these findings.
Systematic Review of the Operative Risks of Carotid Endarterectomy for Recently Symptomatic Stenosis in Relation to the Timing of Surgery
Authors: Rerkasem Kittipan , Rothwell Peter M.
Published: August 2009

Background and Purpose—

Reliable data on the risk of carotid endarterectomy (CEA) in relation to timing of surgery are necessary to plan CEA most effectively, to adjust risks for case-mix, and to understand the mechanisms of operative stroke.

Methods—

We performed a systematic review of all studies published from 1980 to 2008 inclusive that reported the risk of stroke and death due to CEA in relation to the time between presenting symptom and surgery. Pooled estimates of risk by the time since the last event were obtained by Mantel–Haenszel meta-analysis.

Results—

Of 494 published operative series, only 47 stratified risk by timing of surgery. The pooled absolute risks of stroke and death after urgent CEA were high in patients with stroke-in-evolution (20.2%, 95% CI 12.0 to 28.4) and in patients with crescendo TIA (11.4%, 6.1 to 16.7), with no trends toward reduced risks in more recent studies. However, there was no significant difference between early and later CEA in neurologically stable patients with recent TIA or nondisabling stroke (<1 week versus ≥1 week, OR=1.2, 0.9 to 1.7,
P
=0.17; <2 weeks versus ≥2 weeks, OR=1.2, 0.9 to 1.6,
P
=0.13).

Conclusions—

Emergency endarterectomy for stroke-in-evolution has a high operative risk, but the risk may be somewhat lower in patients with crescendo TIA. Surgery in the first week in neurologically stable patients with TIA or minor stroke is not associated with a substantially higher operative risk than delayed surgery. More data are required on the risk and benefit of more urgent surgery for TIA and minor stroke and for early versus delayed surgery in patients with major nondisabling stroke.
Dually Supplied T-Junctions in Arteriolo-Arteriolar Anastomosis in Mice
Authors: Toriumi Haruki , Tatarishvili Jemal , Tomita Minoru , Tomita Yutaka , Unekawa Miyuki , Suzuki Norihiro
Published: August 2009

Background and Purpose—

The functional role of arteriolo-arteriolar anastomosis (AAA) between the middle cerebral artery (MCA) and anterior cerebral artery in local hemodynamics is unknown, and was investigated here.

Methods—

Blood flow in AAAs was examined using fluorescein isothiocyanate–labeled red blood cells (RBCs) as a flow indicator in 16 anesthetized C57BL/6J mice before and after MCA occlusion up to 7 experimental days.

Results—

We observed paradoxical flow in AAAs; labeled RBCs entered from both the MCA and anterior cerebral artery sides and the opposing flows met at a branching T-junction, where the flows combined and passed into a penetrating arteriole. The dually fed T-junction was not fixed in position, but functionally jumped to adjacent T-junctions in response to changing hemodynamic conditions. On MCA occlusion, RBC flow from the MCA side immediately stopped. After a period of “hesitation,” blood started to move retrogradely in one of the MCA branches toward the MCA stem. The retrograde blood flow was statistically significantly (
P
<0.05), serving to feed blood to other MCA branches after a lag period. In capillaries, MCA occlusion induced immediate RBC disappearance in the ischemic core and to a lesser extent in the marginal zone near AAAs. At day 3 after ischemia, we recognized the beginning of remodeling with angiogenesis centering on AAAs.

Conclusions—

AAAs appear to play a key role in local hemodynamic homeostasis, both in the normal state and in the development of collateral channels and revascularization during ischemia.
Advance Health Care Directives: Towards a Coordinated European Policy?
Authors: Andorno Roberto , Brauer Susanne , Biller-Andorno Nikola
Published: August 2009

The aim of this paper is to compare the different existing approaches to advance health care directives within the European context, and to explore the possibility of reaching a deeper consensus among countries on this subject. To this end, it first discusses the shortcomings of Article 9 of the Council of Europe's Biomedicine Convention. Second, it offers a comparative analysis of the legal status of advance directives in a number of European countries. Finally, it presents the conclusions of an international interdisciplinary workshop focused on this topic that was held in Zurich in June 2008.
Biobank Research: Reporting Results to Individual Participants
Authors: Bovenberg Jasper , Gevers Sjef , Meulenkamp Tineke , Smets Ellen
Published: August 2009

Over the last years we conducted an extensive study on the question whether and, if so, how, any results to be derived from research with large scale biobanks shoud be communicated to individual research participants. More specifically, our research intended (1) to assess the attitudes and information preferences of major stakeholders (participants/researchers), and (2) to examine whether there are any legal obligations of researchers to provide feedback to individuals. Our aim was to elaborate a general normative framework that could provide (further) guidance in this matter and be taken into account in the establishment and operation of biobanks. In this article, we first summarize the results of the empirical study on attitudes and preferences; subsequently, address the legal aspects. The article ends with a section that discusses our main findings and provides the basis for the guiding principles we propose; the principles themselves are located in an Annex.
Stable Boundary Layer Depth from High-Resolution Measurements of the Mean Wind Profile
Authors: Pichugina Yelena L. , Banta Robert M.
Published: August 2009

The depth h of the stable boundary layer (SBL) has long been an elusive measurement. In this diagnostic study the use of high-quality, high-resolution (Δz = 10 m) vertical profile data of the mean wind U(z) and streamwise variance σu2(z) is investigated to see whether mean-profile features alone can be equated with h. Three mean-profile diagnostics are identified: hJ, the height of maximum low-level-jet (LLJ) wind speed U in the SBL; h1, the height of the first zero crossing or minimum absolute value of the magnitude of the shear ∂U/∂z profile above the surface; and h2, the minimum in the curvature ∂2U/∂z2 profile. Boundary layer BL here is defined as the surface-based layer of significant turbulence, so the top of the BL was determined as the first significant minimum in the σu2(z) profile, designated as hσ. The height hσ was taken as a reference against which the three mean-profile diagnostics were tested. Mean-wind profiles smooth enough to calculate second derivatives were obtained by averaging high-resolution Doppler lidar profile data, taken during two nighttime field programs in the Great Plains, over 10-min intervals. Nights are chosen for study when the maximum wind speed in the lowest 200 m exceeded 5 m s−1 (i.e., weak-wind, very stable BLs were excluded). To evaluate the three diagnostics, data from the 14-night sample were divided into three profile shapes: Type I, a traditional LLJ structure with a distinct maximum or “nose,” Type II, a “flat” structure with constant wind speed over a significant depth, and Type III, having a layered structure to the shear and turbulence in the lower levels. For Type I profiles, the height of the jet nose hJ, which coincided with h1 and h2 in this case, agreed with the reference SBL depth to within 5%. The study had two major results: 1) among the mean-profile diagnostics for h, the curvature depth h2 gave the best results; for the entire sample, h2 agreed with hσ to within 12%; 2) considering the profile shapes, the layered Type III profiles gave the most problems. When these profiles could be identified and eliminated from the sample, regression and error statistics improved significantly: mean relative errors of 8% for hJ and h1, and errors of <5% for h2, were found for the sample of only Type I and II profiles.
Application of Object-Based Verification Techniques to Ensemble Precipitation Forecasts
Authors: Gallus William A.
Published: August 2009

Both the Method for Object-based Diagnostic Evaluation (MODE) and contiguous rain area (CRA) object-based verification techniques have been used to analyze precipitation forecasts from two sets of ensembles to determine if spread-skill behavior observed using traditional measures can be seen in the object parameters. One set consisted of two eight-member Weather Research and Forecasting (WRF) model ensembles: one having mixed physics and dynamics with unperturbed initial and lateral boundary conditions (Phys) and another using common physics and a dynamic core but with perturbed initial and lateral boundary conditions (IC/LBC). Traditional measures found that spread grows much faster in IC/LBC than in Phys so that after roughly 24 h, better skill and spread are found in IC/LBC. These measures also reflected a strong diurnal signal of precipitation. The other set of ensembles included five members of a 4-km grid-spacing WRF ensemble (ENS4) and five members of a 20-km WRF ensemble (ENS20). Traditional measures suggested that the diurnal signal was better in ENS4 and spread increased more rapidly than in ENS20.

Standard deviations (SDs) of four object parameters computed for the first set of ensembles using MODE and CRA showed the trend of enhanced spread growth in IC/LBC compared to Phys that had been observed in traditional measures, with the areal coverage of precipitation exhibiting the greatest growth in spread with time. The two techniques did not produce identical results; although, they did show the same general trends. A diurnal signal could be seen in the SDs of all parameters, especially rain rate, volume, and areal coverage. MODE results also found evidence of a diurnal signal and faster growth of spread in object parameters in ENS4 than in ENS20.

Some forecasting approaches based on MODE and CRA output are also demonstrated. Forecasts based on averages of object parameters from each ensemble member were more skillful than forecasts based on MODE or CRA applied to an ensemble mean computed using the probability matching technique for areal coverage and volume, but differences in the two techniques were less pronounced for rain rate and displacement. The use of a probability threshold to define objects was also shown to be a valid forecasting approach with MODE.
Are the" Best" Teachers in the "Neediest" Schools?
Authors: De Luca Barbara M. , Takano Kaori , Hinshaw Steven A. , Raisch C. Daniel
Published: August 2009

The purpose of this research was to determine the relationship between distribution of teacher resources and student need. The effort was to determine if the "best" teachers are teaching the "neediest" students in the elementary schools in the "Big 8" urban school districts in Ohio as equity principles would mandate. Using Pearson correlation analysis, we investigated the relationship between average teacher salary (used to measure teacher quality) and percent of disadvantaged students as well as level of student achievement (both measures of student need) for all public elementary schools in each of the eight districts. In general, the findings show that as the percent of disadvantaged students increased, average teacher salary decreased for the statistically significant relationships. Furthermore, as student achievement increased, average teacher salary increased. Both sets of findings suggest that the "best" teachers are not teaching the "neediest" students.
Retrieval Strategies for Multi-tier Automated Carousel Conveyors with Multiple Robots
Authors: Lin Li  , Bozer Yavuz A.
Published: August 2009

Carousel conveyors (also known simply as “carousels”) are an important and well-known type of material handling system used in warehousing and manufacturing to store/retrieve small-to-medium-sized parts. A traditional multi-tier (or multi-level) carousel, which is powered by a single drive, rotates as a whole unit, and brings the items to the input/output point one at a time, since each level cannot be rotated independently. A special type of carousel (also known as a “rotary rack”) uses a dedicated drive for each level of the carousel. This allows each level of the carousel to rotate independently of and concurrently with the other levels. It also allows a rotary rack to support multiple pickers (or robots) while a traditional carousel can support typically only one picker. Although rotary racks have been available for quite some time, questions about their performance and efficient use remain largely unanswered, especially in comparison with traditional carousels, which have been the subject of numerous studies. Assuming one or more picking robots, in this paper we use a simulation model to develop and analyze four retrieval strategies for a rotary rack. We compare the performance of the four strategies as a function of the input data and the number of robots in the system. We also address the question of the appropriate number of robots. As one would expect, the simulation results indicate that the throughput of the system increases with the number of robots. However, more robots also lead to more idle time per robot. We show the tradeoff between the expected time required to process an order and the expected idle time per robot.
Sliding mode controlled bioreactor using a time-varying sliding surface
Authors: Tokat S.
Published: August 2009

Bioreactor processes based on substrate concentration have both highly non-linear behaviour and parameter uncertainties mostly bounded with physical and biological constraints, which make them a subject area of sliding mode control. This work deals with sliding mode control of a fermentation process in a continuous stirred bioreactor. A new sliding surface is defined using angular information as a function of time that provides adjustable continuous movement of the sliding surface. Computer simulations are presented to show the effectiveness and efficiency of the proposed method and to make a quantitative comparison with the conventional sliding mode controller having a constant sliding surface. The excess amount of substrate concentration in the mixture causes undesired by-product information. Therefore, the substrate concentration should not stay above its desired value for a long time. It is shown in the simulations that the performance of the proposed method, especially in regard to the settling time of the substrate concentration and reaching time, is improved. It is also shown that different system state trajectories could be obtained with the proposed method by adjusting the defined parameters of the angular information.
Formaldehyde exposure risk in air-conditioned offices of Hong Kong
Authors: Mui KW , Wong LT , Hui PS , Chan WY
Published: August 2009

Formaldehyde (HCHO) is a carcinogenic toxicant commonly present in an air-conditioned office environment. This study examines the lifetime exposure risk of HCHO in air-conditioned offices of Hong Kong under various indoor environmental conditions. Using the regional indoor air quality assessment results of 511 Hong Kong offices recorded from 1996 to 2005, together with the mathematical correlations among HCHO exposure concentration, ventilation and thermal environment verified at 43 other local air-conditioned offices, the exposure risk in terms of loss of life expectancy (USEPA standard) was predicted for an office environment preset at certain air temperature and atmospheric carbon dioxide (CO 2) level. It was reported that the average increment of HCHO exposure risk was 2% for every 1°C increment in the air temperature range of 22.5—25.5°C, or 2.5% for every 10 ppm increment in the CO2 concentration range of 800—1000 ppm. This study presents useful information on HCHO exposure risk evaluation for air-conditioned offices associated with various policies on indoor air temperature and ventilation demands.

Practical applications: This study outlines an approach to lifetime exposure risk assessment for HCHO inhaled in air-conditioned offices of Hong Kong under various indoor environmental conditions. In a typical office environment, the findings demonstrated that the average increment of HCHO exposure risk was 2% for every 1°C increment in air temperature or 2.5% for every 10 ppm increment in CO 2 concentration.
Benefit of Corticosteroid Therapy in Angelman Syndrome
Authors: Forrest Katharine M. L. , Young Helen , Dale Russell C. , Gill Deepak S.
Published: August 2009

Angelman syndrome is often associated with an intractable seizure disorder. We describe 4 children who demonstrated an excellent response to corticosteroid therapy. The benefits included not only reduction in clinical seizures but also modification of the ``typical'' Angelman electroencephalogram. In addition, there was improvement in the myoclonic jerks, sleep pattern, and developmental progress. Corticosteroids appeared to have a broad benefit on the epileptic encephalopathy. We believe that these cases pose a challenge to the conventional management of intractable epilepsy in Angelman syndrome.
To Mother or Matter
Authors: Schultheiss Donna E. Palladino
Published: August 2009

Despite a burgeoning interest in the interface between work and relationships, and its origins in feminist thought, crucial aspects of women’s experiences have remained invisible in the face of mainstream discourse in the career field. Many women have and will continue to define motherhood as a career, yet none of our career development theories do so. In this article, an historical, sociocultural, and political framework for the context of the career development of women who mother is offered. Existing career theory is discussed in light of women’s mothering work and a relational cultural paradigm is offered as a theoretical backdrop for the consideration of critical issues relevant to women’s work. Implications for career counseling practice, research, and public policy are offered.
Global Spread of Radical Ideologies
Authors: Gupta Dipak K.
Published: August 2009

One of Professor David Rapoport's contributions to academic inquiries into terrorism is his theory of waves of international terrorism. Rapoport argues that there have been four waves in the history of modern terrorism, where an idea has spurred violence across the world. Although his idea has become mainstream there is no research on how ideas actually spread. This article attempts to bridge this important gap by combining recent advances in the fields of business, advertisement and mass communication with research on terrorism. It is argued that understanding the process by which these ideas spread across the world can provide us with the tool to manage future waves of international terrorism.
Migration Remittances
Authors: Panda Rajaram
Published: August 2009

Remittances are increasingly identified as golden eggs that contribute crucially to the foreign exchange earnings of many developing countries across the world. Governments and international agencies have recognised that remittances to the developing world are substantially greater than aid. Though the global flow of such remittances is in the vicinity of $150–200 billion, remittances to South Asia alone total perhaps $40–50 billion. Much of these remittances are done through unofficial mechanisms and procedures, via informal value transfer systems and are, therefore, unregulated and uncontrolled. Proliferating migrant social networks and the emergence of a vibrant immigration industry, have given a momentum to international migration.

Remittances generate both micro and macro-economic effects. In microeconomic terms, remittances make an important welfare contribution to the receiving household, besides providing a cushion during an economic downturn or following natural disasters. They also generate ripple effects impacting extended family and community beyond the receiving household due to increased consumption. In macroeconomic terms, remittances provide a stable flow of funds that is often counter-cyclical and an important source of foreign exchange for many countries.

The argument in this article concentrates on the economic and financial linkages that the Indian diasporic community has maintained with the mother country and their relevance to the developmental programmes in India.
Modeling and Characterization of a Linear Piezomotor
Authors: Arafa Mustafa , Aldraihem Osama , Baz Amr
Published: August 2009

This article presents the modeling and characterization of a new class of piezoelectric linear motor. The motor relies in its operation on a set of piezoelectric bimorphs which are sequentially activated to linearly move a drive rod along spring loaded rollers. Emphasis in this article is placed on studying the dynamic behavior of this class of piezoelectric motors, both theoretically and experimentally, in an effort to predict the piezomotor response to various loads and excitation schemes. To this end, a numerical model has been developed to simulate the dynamics of the piezoelectric bimorphs comprising the piezomotor. Friction between the bimorph elements and the drive rod are handled using an appropriate friction model. Experimental testing of the motor is carried out to validate the predictions of the theoretical model.
Semiactive Backstepping Control for Vibration Reduction in a Structure with Magnetorheological Damper Subject to Seismic Motions
Authors: Zapateiro Mauricio , Karimi Hamid Reza , Luo Ningsu , Phillips Brian M. , Spencer Billie F.
Published: August 2009

The use of magnetorheological (MR) dampers for mitigating vibrations caused by seismic motions in civil engineering structures has attracted much interest in the scientific community because of the advantages of this class of device. It is known that MR dampers can generate high damping forces with low energy requirements and low cost of production. However, the complex dynamics that characterize MR dampers make difficult the control design for achieving the vibration reduction goals in an efficient manner. In this article, a semiactive controller based on the backstepping technique is proposed. The controller was applied to a three-story building with an MR damper at its first floor subjected to seismic motions. The performance of the controller was evaluated experimentally by means of real time hybrid testing.
Educating Teachers to Transform the Trilogy
Authors: Colley Bernadette
Published: August 2009

This article constitutes the second stage in an ongoing investigation of alternative instrumental ensembles in schools. First, interview data from the previous stage, which documented cases in Massachusetts, Kentucky, Washington, and Nevada, where individual music teachers began and successfully sustained alternative ensembles for the past 5 to 10 years, summarize the genesis, growth, and sustenance of these ensembles. The current article presents data relating to the K-12 policy decisions made by these teachers and then examines these policy decisions with a focus on their implications for music teacher preparation. Implications for music teacher education are considered in light of enhancing music teachers’ understanding of policy choices in the areas of (a) program design, (b) student participation, (c) conceptualizations of musicianship, and (d) cultural and aesthetic appropriateness. Finally, differences in inherent assumptions between alternative ensemble practice and traditional ensemble practice are set forth, ending with recommendations for specific teacher education reforms and action initiatives.
Environmental Fit
Authors: Blakeley-Smith Audrey , Carr Edward G. , Cale Sanja I. , Owen-DeSchryver Jamie S.
Published: August 2009

Theoretical considerations suggest that problem behavior should increase when a child’s competency does not match the curricular demands of the environment (i.e., when there is poor environmental fit). In the present study, environmental fit was examined for six children with autism spectrum disorders. Results indicated that the children exhibited high rates of problem behavior associated with poor motor or academic competency. Curricular modifications resulted in (a) a decrease in the level of problem behavior, (b) an increase in the percentage of task steps completed correctly, and (c) improved affect. Adults who worked with the children reported ease of intervention techniques. The concept of environmental fit and its usefulness in guiding both assessment of and intervention for problem behavior are discussed.
Home Beyond Home
Authors: Michael Mike , Gaver William
Published: August 2009

This article attempts to explore “dwelling” in the contemporary technonatural world through a series of novel interventions in the home. In particular, users' reactions to one of three “threshold devices”—the video window, the local barometer, and the plane tracker—are studied ethnographically. Drawing on Heidegger, the authors interpret the opaque functionality of these technologies as “poetical” insofar as they facilitate users' access to the heterogeneity, ambiguity, and complexity of the technonatural world within which the home is situated. Such access, the authors suggest, can resource a dwelling through which “care” can be enacted. Some of the methodological and political implications of such devices are discussed.
Keeping & Dwelling
Authors: Latimer Joanna , Munro Rolland
Published: August 2009

This article explores the topic of home in terms of the art of dwelling. We set out to show that what people “keep” affects their experience of dwelling. Keeping, in this analysis, grants relational extension (Latimer 2009a, 2009b; Munro, 1996; Strathern, 1991; Latimer and Munro 2006), creating and reproducing worlds that bind. As we illustrate, the meaning of home for Euro-Americans can be understood as gravitating from feelings of belonging being anchored within specific locales to matters of identity being entangled in locutions that address the figure of self. In taking up Heidegger's (1978) argument that dwelling is thinking as much as it is “building,” we go on to trouble how reflection, when conducted in the mode of comparison rather than contemplation, conflates keeping with issues of choice.
Assessing disability progression with the Multiple Sclerosis Functional Composite
Authors: Rudick RA , Polman CH , Cohen JA , Walton MK , Miller AE , Confavreux C , Lublin FD , Hutchinson M , O’Connor PW , Schwid SR , Balcer LJ , Lynn F , Panzara MA , Sandrock AW
Published: August 2009

Background

The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event.

Objective

Evaluate a new method for analyzing disability progression using the MSFC.

Methods

MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for ≥3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects.

Results

Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL.

Conclusion

MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies.
Course of neuromyelitis optica during inadvertent pregnancy in a patient treated with rituximab
Authors: Pellkofer HL , Suessmair C , Schulze A , Hohlfeld R , Kuempfel T
Published: August 2009

In neuromyelitis optica (NMO), the monoclonal B-cell antibody rituximab is a therapeutic option. Little is known about the course of NMO and the safety of rituximab during pregnancy. In this study, we report the clinical course of a patient with NMO after application of rituximab 1 week before inadvertent conception. Mother and child did not experience any adverse event, and the postpartum development of the baby was completely normal up to 15 months. Clinical course of NMO was stable during the entire pregnancy. This case illustrates a favorable outcome in a pregnant NMO patient and her child after therapy with rituximab.