bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods to detect and analyze copy number variations at the genome-wide and locus-specific levels
Authors: Lee J.H. , Jeon J.T.
Published: March 2009

Copy number variations (CNVs) have effects on phenotypes by altering transcription levels of genes and may have major impacts on protein sequence, structure and function. Therefore, CNV screening and analysis focused on the identification of CNV-genetic disease relations are actively progressing. CNVs can be detected and analyzed by various methodologies at the genome-wide and locus-specific levels. The genome-wide analysis of CNVs has been enhanced by bioinformatic tools for long-range sequence analysis, and comparative genome hybridization using microarrays containing either single nucleotide polymorphisms or bacterial artificial chromosome clones that represent the whole genome. RFLP followed by Southern blot analysis, quantitative real-time PCR, pyrosequencing, ligation detection reaction and the invader assay have become the main tools for locus-specific analysis so far. In this review, we present a brief principle, application history, and strengths and weaknesses of the methods used to detect CNVs at the genome-wide and locus-specific levels.
Computational methods for identification of recurrent copy number alteration patterns by array CGH
Authors: Shah S.P.
Published: March 2009

Recurrent DNA copy number alterations (CNA) are widely studied in diagnostic and cytogenetic cancer research. CNAs reveal locations that may alter gene dosage and thus expression of the genes contained within. Array comparative genomic hybridization has emerged as a popular high-throughput, genome-wide technique to interrogate tumor genomes for copy number alterations. When studying a group of tumors derived from a patient cohort, it is of great interest to detect the copy number alterations that are common across the population and thus assumed to be potential diagnostic markers and/or predictors of clinical outcome. In this paper, we review extant and available computational approaches for detecting such recurrent copy number alterations from array comparative genomic hybridization (aCGH) data. This is a challenging computational problem due to various sources of noise in the data that can obscure the recurrent copy number signals or induce false positives in their prediction. In this paper, we qualitatively evaluate methods designed to detect recurrent copy number alterations for aCGH data based on their analytical strengths and limitations, and discuss expected future directions in this important area of cancer research.
Sex Differences in Acclimation of Hypothalamic Arcuate Glucokinase Gene and Protein Expression to Repeated Intermediate Insulin Administration
Authors: Nedungadi T. Prashant , Genabai Naresh K. , Parihar Manish , Briski Karen P.
Published: March 2009

Background: Repeated intermediate-acting insulin administration attenuates genomic reactivity of neurons in key autonomic metabolic structures in the male, but not female rat brain – results that support a central neural component of sex-specific response desensitization. The glucokinase (GK) enzyme functions as a glucose sensor in a body-wide system of metabolic monitoring structures, including the brain, and is expressed at high levels in the hypothalamic arcuate nucleus (ARH). Method: Quantitative real-time RT-PCR was used to investigate the hypothesis that habituation of ARH GK gene expression to neutral protamine Hagedorn insulin (NPH) injection differs among sexes. In lieu of evidence for region-based functional heterogeneity in this structure, effects of NPH on in situ GK protein-staining patterns were evaluated at different rostrocaudal levels of the ARH by immunocytochemistry. Results: Basal ARH GK mRNA levels were equivalent in sham-operated (SHAM) and orchidectomized (ORDX) male rats. SHAM males exhibited augmented GK gene profiles in response to acute NPH injection, as well as elevated numbers of GK-immunoreactive (-ir) neurons in the rostral ARH. ORDX abolished this stimulatory transcriptional response, but did not prevent increased GK labeling throughout this structure. Stimulatory effects of precedent insulin administration on baseline GK mRNA were reversed by ORDX. Serial dosing of SHAM males with NPH elicited no change in ARH GK transcription, but decreased GK-ir in the rostral ARH. Acute NPH injection had no impact on GK gene profiles in estradiol benzoate (EB)- or oil-implanted ovariectomized (OVX) female rats, but diminished GK-ir cell counts in the OVX + EB caudal ARH. Precedent NPH treatment did not modify baseline GK mRNA levels in either group of females, but resulted in decreased or elevated GK gene and protein expression during recurring injection in the presence or absence of EB, respectively. Conclusion: These results provide novel evidence for sex-specific patterns of acclimation of GK mRNA and protein expression within the rat ARH to serial NPH injection, and support the need to elucidate the physiological ramifications of these adaptations regarding behavioral and physiological responses to recurring intermediate insulin administration.
Genipin Cross-Linked Fibrin Hydrogels for in vitro Human Articular Cartilage Tissue-Engineered Regeneration
Authors: Dare Emma V. , Griffith May , Poitras Philippe , Kaupp James A. , Waldman Stephen D. , Carlsson David J. , Dervin Geoffrey , Mayoux Christine , Hincke Maxwell T.
Published: March 2009

Our objective was to examine the potential of a genipin cross-linked human fibrin hydrogel system as a scaffold for articular cartilage tissue engineering. Human articular chondrocytes were incorporated into modified human fibrin gels and evaluated for mechanical properties, cell viability, gene expression, extracellular matrix production and subcutaneous biodegradation. Genipin, a naturally occurring compound used in the treatment of inflammation, was used as a cross-linker. Genipin cross-linking did not significantly affect cell viability, but significantly increased the dynamic compression and shear moduli of the hydrogel. The ratio of the change in collagen II versus collagen I expression increased more than 8-fold over 5 weeks as detected with real-time RT-PCR. Accumulation of collagen II and aggrecan in hydrogel extracellular matrix was observed after 5 weeks in cell culture. Overall, our results indicate that genipin appeared to inhibit the inflammatory reaction observed 3 weeks after subcutaneous implantation of the fibrin into rats. Therefore, genipin cross-linked fibrin hydrogels can be used as cell-compatible tissue engineering scaffolds for articular cartilage regeneration, for utility in autologous treatments that eliminate the risk of tissue rejection and viral infection.
Sphingomyelin Synthase 2 Is One of the Determinants for Plasma and Liver Sphingomyelin Levels in Mice
Authors: Liu Jing , Zhang Hongqi , Li Zhiqiang , Hailemariam Tiruneh K. , Chakraborty Mahua , Jiang Kailiu , Qiu Daniel , Bui Hai H. , Peake David A. , Kuo Ming-Shang , Wadgaonkar Raj , Cao Guoqing , Jiang Xian-Cheng
Published: March 2009

Background—

It has been proposed that plasma sphingomyelin (SM) plays a very important role in plasma lipoprotein metabolism and atherosclerosis. Sphingomyelin synthase (SMS) is the last enzyme for SM de novo biosynthesis. Two SMS genes, SMS1 and SMS2, have been cloned and characterized.

Methods and Results—

To evaluate the in vivo role of SMS2 in SM metabolism, we prepared SMS2 knockout (KO) and SMS2 liver-specific transgenic (LTg) mice and studied their plasma SM and lipoprotein metabolism. On a chow diet, SMS2 KO mice showed a significant decrease in plasma SM levels (25%,
P
<0.05), but no significant changes in total cholesterol, total phospholipids, or triglyceride, compared with wild-type (WT) littermates. On a high-fat diet, SMS2 KO mice showed a decrease in plasma SM levels (28%,
P
<0.01), whereas SMS2LTg mice showed a significant increase in those levels (29%,
P
<0.05), but no significant changes in other lipids, compared with WT littermates. Atherogenic lipoproteins from SMS2LTg mice displayed a significantly stronger tendency toward aggregation after mammalian sphingomyelinase treatment, compared with controls. Moreover, SMS2 deficiency significantly increased plasma apoE levels (2.0-fold,
P
<0.001), whereas liver-specific SMS2 overexpression significantly decreased those levels (1.8-fold,
P
<0.01). Finally, SMS2 KO mouse plasma promoted cholesterol efflux from macrophages, whereas SMS2LTg mouse plasma prevented it.

Conclusions—

We therefore believe that regulation of liver SMS2 activity could become a promising treatment for atherosclerosis.
The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow
Authors: Hahn Cornelia , Orr A. Wayne , Sanders John M. , Jhaveri Krishna A. , Schwartz Martin Alexander
Published: March 2009

Atherosclerosis begins as local inflammation of artery walls at sites of disturbed flow. JNK (c-Jun NH
2
-terminal kinase) is thought to be among the major regulators of flow-dependent inflammatory gene expression in endothelial cells in atherosclerosis. We now show that JNK activation by both onset of laminar flow and long-term oscillatory flow is matrix-specific, with enhanced activation on fibronectin compared to basement membrane protein or collagen. Flow-induced JNK activation on fibronectin requires new integrin ligation and requires both the mitogen-activated protein kinase kinase MKK4 and p21-activated kinase. In vivo, JNK activation at sites of early atherogenesis correlates with the deposition of fibronectin. Inhibiting p21-activated kinase reduces JNK activation in atheroprone regions of the vasculature in vivo. These results identify JNK as a matrix-specific, flow-activated inflammatory event. Together with other studies, these data elucidate a network of matrix-specific pathways that determine inflammatory events in response to fluid shear stress.
Akt-Mediated Transactivation of the S1P
1
Receptor in Caveolin-Enriched Microdomains Regulates Endothelial Barrier Enhancement by Oxidized Phospholipids
Authors: Singleton Patrick A. , Chatchavalvanich Santipongse , Fu Panfeng , Xing Junjie , Birukova Anna A. , Fortune Jennifer A. , Klibanov Alexander M. , Garcia Joe G. N. , Birukov Konstantin G.
Published: March 2009

Endothelial cell (EC) barrier dysfunction results in increased vascular permeability, leading to increased mass transport across the vessel wall and leukocyte extravasation, the key mechanisms in pathogenesis of tissue inflammation and edema. We have previously demonstrated that OxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-
sn
-glycero-3-phosphocholine) significantly enhances vascular endothelial barrier properties in vitro and in vivo and attenuates endothelial hyperpermeability induced by inflammatory and edemagenic agents via Rac and Cdc42 GTPase dependent mechanisms. These findings suggested potential important therapeutic value of barrier-protective oxidized phospholipids. In this study, we examined involvement of signaling complexes associated with caveolin-enriched microdomains (CEMs) in barrier-protective responses of human pulmonary ECs to OxPAPC. Immunoblotting from OxPAPC-treated ECs revealed OxPAPC-mediated rapid recruitment (5 minutes) to CEMs of the sphingosine 1-phosphate receptor (S1P
1
), the serine/threonine kinase Akt, and the Rac1 guanine nucleotide exchange factor Tiam1 and phosphorylation of caveolin-1, indicative of signaling activation in CEMs. Abolishing CEM formation (methyl-β-cyclodextrin) blocked OxPAPC-mediated Rac1 activation, cytoskeletal reorganization, and EC barrier enhancement. Silencing (small interfering RNA) Akt expression blocked OxPAPC-mediated S1P
1
activation (threonine phosphorylation), whereas silencing S1P
1
receptor expression blocked OxPAPC-mediated Tiam1 recruitment to CEMs, Rac1 activation, and EC barrier enhancement. To confirm our in vitro results in an in vivo murine model of acute lung injury with pulmonary vascular hyperpermeability, we observed that selective lung silencing of caveolin-1 or S1P
1
receptor expression blocked OxPAPC-mediated protection from ventilator-induced lung injury. Taken together, these results suggest Akt-dependent transactivation of S1P
1
within CEMs is important for OxPAPC-mediated cortical actin rearrangement and EC barrier protection.
Swallowing Disturbance Pattern Relates to Brain Lesion Location in Acute Stroke Patients
Authors: Steinhagen Volker , Grossmann Annette , Benecke Reiner , Walter Uwe
Published: March 2009

Background and Purpose—

The relationship of brain lesion location and swallowing disturbance pattern has been poorly studied in acute stroke patients.

Methods—

Sixty patients with first-ever acute ischemic stroke at clearly assessed location and clinical signs of dysphagia were studied. Swallowing-related parameters rated clinically and fiberendoscopically were attention deficit, buccofacial apraxia, orofacial paresis, gag reflex, delay of pharyngeal swallow, pharyngeal contraction, larynx elevation, function of upper esophageal sphincter (UES), and aspiration severity.

Results—

Attention deficit was independently predicted only by parietotemporal infarction, buccofacial apraxia by left-sided parietotemporal infarction, orofacial paresis by infarction encompassing upper motor neuron of cranial nerves, and impaired UES opening by lateral medullary infarction. Other swallowing parameters were not related to lesion topology. On posthoc analysis, pneumonia within 21 days after stroke was predicted only by insular lesion.

Conclusions—

Distinct acute brain lesion locations result in characteristic swallowing disturbance patterns. Dysphagic patients with insular stroke appear to have even higher risk of pneumonia suggesting a further associated factor promoting infection in these subjects.
Cerebrovascular Reactivity Measured by Near-Infrared Spectroscopy
Authors: Lee Jennifer K. , Kibler Kathleen K. , Benni Paul B. , Easley R. Blaine , Czosnyka Marek , Smielewski Peter , Koehler Raymond C. , Shaffner Donald H. , Brady Ken M.
Published: March 2009

Background and Purpose—

The pressure reactivity index (PRx) describes cerebral vessel reactivity by correlation of slow waves of intracranial pressure (ICP) and arterial blood pressure. In theory, slow changes in the relative total hemoglobin (rTHb) measured by near-infrared spectroscopy are caused by the same blood volume changes that cause slow waves of ICP. Our objective was to develop a new index of vascular reactivity, the hemoglobin volume index (HVx), which is a low-frequency correlation of arterial blood pressure and rTHb measured with near-infrared spectroscopy.

Methods—

Gradual hypotension was induced in piglets while cortical laser-Doppler flux was monitored. ICP was monitored, and rTHb was measured continuously using reflectance near-infrared spectroscopy. The HVx was recorded as a moving linear correlation between slow waves (20 to 300 seconds) of arterial blood pressure and rTHb. Autoregulation curves were constructed by averaging values of the PRx or HVx in 5-mm Hg bins of cerebral perfusion pressure.

Results—

The laser-Doppler flux-determined lower limit of autoregulation was 29.4±6.7 mm Hg (±SD). Coherence between rTHb and ICP was high at low frequencies. HVx was linearly correlated with PRx. The PRx and HVx both showed higher values below the lower limit of autoregulation and lower values above the lower limit of autoregulation. Areas under the receiver operator characteristic curves were 0.88 and 0.85 for the PRx and HVx, respectively.

Conclusions—

Coherence between the rTHb and ICP waveforms at the frequency of slow waves suggests that slow waves of ICP are related to blood volume changes. The HVx has potential for further development as a noninvasive alternative to the PRx.
Carotid Repair Using Autologous Adipose-Derived Endothelial Cells
Authors: Froehlich Harald , Gulati Rajiv , Boilson Barry , Witt Tyra , Harbuzariu Adriana , Kleppe Laurel , Dietz Allan B. , Lerman Amir , Simari Robert D.
Published: March 2009

Background and Purpose—

Adipose tissue is an abundant source of endothelial cells as well as stem and progenitor cells which can develop an endothelial phenotype. It has been demonstrated that these cells have distinct angiogenic properties in vitro and in vivo. However, whether these cells have the capacity to directly improve large vessel form and function after vascular injury remains unknown. To define whether delivery of adipose-derived endothelial cells (ADECs) would improve healing of injured carotid arteries, a rabbit model of acute arterial injury was used.

Methods—

Autologous rabbit ADECs were generated using defined culture conditions. To test the ability of ADECs to enhance carotid artery repair, cells were delivered intraarterially after acute balloon injury. Additional delivery studies were performed after functional selection of cells before delivery.

Results—

After rabbit omental fat harvest and digestion, a proliferative, homogenous, and distinctly endothelial population of ADECs was identified. Direct delivery of autologous ADECs resulted in marked reendothelialization 48 hours after acute vascular injury as compared to saline controls (82.2±26.9% versus 4.2±3.0%
P
<0.001). Delivery of ADECs that were selected for their ability to take up acetylated LDL significantly improved vasoreactivity and decreased intimal formation after vascular injury.

Conclusions—

Taken together, these data suggest that ADECs represent an autologous source of proliferative endothelial cells, which demonstrate the capacity to rapidly improve reendothelialization, improve vascular reactivity, and decrease intimal formation in a carotid artery injury model.
Placebo-Controlled Trial of High-Dose Atorvastatin in Patients With Severe Cerebral Small Vessel Disease
Authors: Lavallée Philippa C. , Labreuche Julien , Gongora-Rivera Fernando , Jaramillo Arturo , Brenner David , Klein Isabelle F , Touboul Pierre-Jean , Vicaut Eric , Amarenco Pierre
Published: March 2009

Background and Purpose—

Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease.

Methods—

Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations.

Results—

At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5–14.7) and carotid (mean, −0.25%; 95% CI, −1.17–0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39–4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries.

Conclusion—

We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.
Cost-Effectiveness of Patient Selection Using Penumbral-Based MRI for Intravenous Thrombolysis
Authors: Earnshaw Stephanie R. , Jackson Dan , Farkouh Ray , Schwamm Lee
Published: March 2009

Background and Purpose—

Better selection of patients for intravenous recombinant tissue plasminogen activator (IV tPA) treatment may improve clinical outcomes. We examined the cost-effectiveness of adding penumbral-based MRI to usual computed tomography (CT)-based methods to identify patients for IV tPA treatment.

Methods—

A decision-analytic model estimated the lifetime costs and outcomes associated with penumbral-based MRI selection in a patient population similar to that enrolled in the IV tPA clinical trials. Inputs were obtained from published literature, clinical trial data, claims databases, and expert opinion. Outcomes included cost per life-year saved and cost per quality-adjusted life-year (QALY) gained. Costs and outcomes were discounted at 3% annually. Sensitivity analyses were conducted.

Results—

The addition of penumbral-based MRI selection increased total cost by $103 over the patient’s remaining lifetime. Penumbral-based MRI selection resulted in favorable outcomes (modified Rankin Scale ≤1) more often than CT-based selection (36.66% versus 35.06%) with an incremental cost per life year of $1840 and an incremental cost per QALY of $1004. Multivariate sensitivity analysis predicted cost-effectiveness (≤$50 000 per QALY) in 99.7% of simulation runs.

Conclusions—

Selecting ischemic stroke patients for IV tPA treatment using penumbral-based MRI after routine CT may increase overall acute care costs, but the benefit is large enough to make this highly cost-effective. This economic analysis lends further support to the consideration of a paradigm shift in acute stroke evaluation.
Fibrinogen Independently Predicts the Development of Ischemic Stroke in a Taiwanese Population
Authors: Chuang Shao-Yuan , Bai Chyi-Huey , Chen Wei-Hung , Lien Li-Ming , Pan Wen-Harn
Published: March 2009

Background and Purpose—

Of few prospective studies that have focused on the relationship between fibrinogen and ischemic stroke (IS) in Asian populations, the findings were inconsistent with those conducted in Western countries. Therefore, we aimed to investigate the temporal relationship between fibrinogen levels (plus several related parameters) and IS in a community-based study in Taiwan.

Methods—

Baseline data from 3281 adults (≥20 years of age) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental IS status derived from insurance claims and death certificate records. Hazard ratios and 95% CIs of clotting factors (fibrinogen, factor VII, factor VIII, and antithrombin-III) for IS events were estimated using Cox proportional hazard models.

Results—

With 10.4 years (average) follow-up, 128 persons developed IS (3.75 per 1000 person-years). As expected, elevated blood pressure and diabetes were independent predictors of IS events. A dose-response relationship was found in univariate analysis between IS risk and tertiles of fibrinogen (hazard ratio, 3.73; 2.19 to 1.00), factor VII (hazard ratio, 1.86; 1.35 to 1.00), and factor VIII (2.97; 1.70 to 1.00), respectively, but not for antithrombin-III. After adjusting for confounding and known risk factors, fibrinogen independently predicted IS events. A 72% increase (hazard ratio, 1.72; 1.02 to 2.90) in IS risk was observed for individuals with fibrinogen ≥8.79 μmol/L compared with those <7.03 μmol/L.

Conclusions—

In addition to hypertension and diabetes, fibrinogen independently predicted future IS risk. We suggest that fibrinogen may be considered in the risk assessment model for IS in the Taiwanese population.
Inducible Nitric Oxide Synthase Promoter Polymorphism Affords Protection Against Cognitive Dysfunction After Carotid Endarterectomy
Authors: Yocum Gene T. , Gaudet John G. , Lee Susie S. , Stern Yaakov , Teverbaugh Lauren A. , Sciacca Robert R. , Emala Charles W. , Quest Donald O. , McCormick Paul C. , McKinsey James F. , Morrissey Nicholas J. , Solomon Robert A. , Connolly E. Sander , Heyer Eric J.
Published: March 2009

Background and Purpose—

Cognitive dysfunction occurs in 9% to 23% of patients during the first month after carotid endarterectomy (CEA). A 4-basepair (AAAT) tandem repeat polymorphism (either 3 or 4 repeats) has been described in the promoter region of inducible nitric oxide synthase (iNOS), a gene with complex roles in ischemic injury and preconditioning against ischemic injury. We investigated whether the 4-repeat variant (iNOS
+
) affects the incidence of cognitive dysfunction after CEA.

Methods—

One-hundred eighty-five CEA and 60 spine surgery (control) subjects were included in this nested cohort analysis. Subjects underwent a battery of 7 neuropsychometric tests before and 1 day and 1 month after surgery. Multivariate logistic regression analyses were performed to determine if the iNOS promoter variant was independently associated with the incidence of cognitive dysfunction at 1 day and 1 month. Further, all right-hand-dominant CEA subjects were grouped by operative side and performance on each test was compared between iNOS
+
and iNOS
−
groups.

Results—

Forty-four of 185 CEA subjects had at least 1 iNOS promoter allele containing 4 copies of the tandem repeat (iNOS
+
). iNOS
+
status was significantly protective against moderate/severe cognitive dysfunction 1 month after CEA. Right-hand-dominant iNOS
+
CEA subjects undergoing left-side CEA performed significantly better than iNOS
−
subjects on a verbal learning test and those undergoing right-side CEA performed significantly better on a test of visuospatial function.

Conclusion—

We demonstrate an iNOS promoter polymorphism variant provides protection against moderate/severe cognitive dysfunction 1 month after CEA. Further, this protection appears to involve cognitive domains localized ipsilateral to the operative carotid artery.
Postcontrast CT Extravasation Is Associated With Hematoma Expansion in CTA Spot Negative Patients
Authors: Ederies Ashraf , Demchuk Andrew , Chia Tze , Gladstone David J. , Dowlatshahi Dar , BenDavit Gabriel , Wong Kelly , Symons Sean P. , Aviv Richard I.
Published: March 2009

Background and Purpose—

The purpose of this study was to assess the effect of postcontrast CT (PCCT) leakage (PCL) on hematoma growth in CTA spot negative patients.

Methods—

A retrospective study of 61 patients presenting within 6 hours of primary ICH onset imaged with CT angiography (CTA) and PCCT. Presence of CTA spot sign and PCL were documented. PCL was defined as the presence of contrast extravasation on the PCCT study at a location remote from the CTA spot sign if present. Hematoma expansion was defined as >6 mL or 30% hematoma enlargement. Patients were dichotomized by CTA spot sign presence and PCL and compared for baseline demographic data, hematoma size, and growth using the unpaired
t
test and Mann-Whitney test for continuous and categorical data, respectively. A probability value <0.05 was considered significant.

Results—

PCL was present in 11/61 patients (18%), occurring in 5 without a spot sign (45%). Spot negative PCL patients demonstrated larger absolute (
P
=0.02) and percentage hematoma growth (
P
=0.02) compared to those without PCL. The mean volume and percent increase was 6.7 mL and 26%, respectively. Inclusion of PCL together with CTA spot sign as risk factor for hematoma expansion increased sensitivity from 0.78 (95% CI; 0.52 to 0.94) to 0.94 (95% CI; 0.72 to 1.00) and NPV from 0.90 (95% CI; 0.76 to 0.97) to 0.97 (95% CI; 0.85 to 1.00).

Conclusion—

Inclusion of PCCT in the investigation of ICH patients allows detection of PCL which, together with the CTA spot sign, increases sensitivity and negative predictive value for predicting hematoma expansion. This finding should be validated in larger studies.
A Climatology of Nocturnal Low-Level Jets at Cabauw
Authors: Baas P. , Bosveld F. C. , Klein Baltink H. , Holtslag A. A. M.
Published: March 2009

A climatology of nocturnal low-level jets (LLJs) is presented for the topographically flat measurement site at Cabauw, the Netherlands. LLJ characteristics are derived from a 7-yr half-hourly database of wind speed profiles, obtained from the 200-m mast and a wind profiler. Many LLJs at Cabauw originate from an inertial oscillation, which develops after sunset in a layer decoupled from the surface by stable stratification. The data are classified to different types of stable boundary layers by using the geostrophic wind speed and the isothermal net radiative cooling as classification parameters. For each of these classes, LLJ characteristics like frequency of occurrence, height above ground level, and the turning of the wind vector across the boundary layer are determined. It is found that LLJs occur in about 20% of the nights, are typically situated at 140–260 m above ground level, and have a speed of 6–10 m s−1. Development of a substantial LLJ is most likely to occur for moderate geostrophic forcing and a high radiative cooling. A comparison with the 40-yr ECMWF Re-Analysis (ERA-40) is added to illustrate how the results can be used to evaluate the performance of atmospheric models.
Urban Flow and Dispersion Simulation Using a CFD Model Coupled to a Mesoscale Model
Authors: Baik Jong-Jin , Park Seung-Bu , Kim Jae-Jin
Published: March 2009

Flow and pollutant dispersion in a densely built-up area of Seoul, Korea, are numerically examined using a computational fluid dynamics (CFD) model coupled to a mesoscale model [fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5)]. The CFD model used is a Reynolds-averaged Navier–Stokes equations model with the renormalization group k − ɛ turbulence model. A one-way nesting method is employed in this study. MM5-simulated data are linearly interpolated in time and space to provide time-dependent boundary conditions for the CFD model integration. In the MM5 simulation, four one-way nested computational domains are considered, and the innermost domain with a horizontal grid size of 1 km covers the Seoul metropolitan area and its adjacent areas, including a part of the Yellow Sea. The NCEP final analysis data are used as initial and boundary conditions for MM5. MM5 is integrated for 48 h starting from 0300 LST 1 June 2004 and the coupled CFD–MM5 model is integrated for 24 h starting from 0300 LST 2 June 2004. During the two-day period, a high-pressure system was dominant over the Korean peninsula, with clear conditions and weak synoptic winds. MM5 simulates local circulations characterized by sea breezes and mountain/valley winds. MM5-simulated synoptic weather and near-surface temperatures and winds are well matched with the observed ones. Results from the coupled CFD–MM5 model simulation show that the flow in the presence of real building clusters can change significantly as the ambient wind speed and direction change. Diurnally varying local circulations mainly cause changes in ambient wind speed and direction in the present simulation. Some characteristic flows—such as the double-eddy circulation, channeling flow, and vertical recirculation vortex—are simulated. Pollutant dispersion pattern and the degree of lateral pollutant dispersion are shown to be complicated in the presence of real building clusters and under varying ambient wind speed and direction. This study suggests that because of the sensitive dependency of urban flow and pollutant dispersion on variations in ambient wind, time-dependent boundary conditions should be used to better simulate or predict them when the ambient wind varies over the period of CFD model simulation.
Optical and Physical Properties of Atmospheric Aerosols over the Bay of Bengal during ICARB
Authors: Nair Vijayakumar S. , Moorthy K. Krishna , Babu S. Suresh , Satheesh S. K.
Published: March 2009

Simultaneous and collocated measurements of total and hemispherical backscattering coefficients (σ and β, respectively) at three wavelengths, mass size distributions, and columnar spectral aerosol optical depth (AOD) were made onboard an extensive cruise experiment covering, for the first time, the entire Bay of Bengal (BoB) and northern Indian Ocean. The results are synthesized to understand the optical properties of aerosols in the marine atmospheric boundary layer and their dependence on the size distribution. The observations revealed distinct spatial and spectral variations of all the aerosol parameters over the BoB and the presence of strong latitudinal gradients. The size distributions varied spatially, with the majority of accumulation modes decreasing from north to south. The scattering coefficient decreased from very high values (resembling those reported for continental/urban locations) in the northern BoB to very low values seen over near-pristine environments in the southeastern BoB. The average mass scattering efficiency of BoB aerosols was found to be 2.66 ± 0.1 m2 g−1 at 550 nm. The spectral dependence of columnar AOD deviated significantly from that of the scattering coefficients in the northern BoB, implying vertical heterogeneity in the aerosol type in that region. However, a more homogeneous scenario was observed in the southern BoB. Simultaneous lidar and in situ measurements onboard an aircraft over the ocean revealed the presence of elevated aerosol layers of enhanced extinction at altitudes of 1 to 3 km with an offshore extent of a few hundred kilometers. Back-trajectory analyses showed these layers to be associated with advection from west Asia and western India. The large spatial variations and vertical heterogeneity in aerosol properties, revealed by the present study, need to be included in the regional radiative forcing over the Bay of Bengal.
The South American Land Data Assimilation System (SALDAS) 5-Yr Retrospective Atmospheric Forcing Datasets
Authors: de Goncalves Luis Gustavo G. , Shuttleworth William J. , Vila Daniel , Larroza Eliane , Bottino Marcus J. , Herdies Dirceu L. , Aravequia Jose A. , De Mattos Joao G. Z. , Toll David L. , Rodell Matthew , Houser Paul
Published: March 2009

The definition and derivation of a 5-yr, 0.125°, 3-hourly atmospheric forcing dataset that is appropriate for use in a Land Data Assimilation System operating across South America is described. Because surface observations are limited in this region, many of the variables were taken from the South American Regional Reanalysis; however, remotely sensed data were merged with surface observations to calculate the precipitation and downward shortwave radiation fields. The quality of this dataset was evaluated against the surface observations available. There are regional differences in the biases for all variables in the dataset, with volumetric biases in precipitation of the order 0–1 mm day−1 and RMSE of 5–15 mm day−1, biases in surface solar radiation of the order 10 W m−2 and RMSE of 20 W m−2, positive biases in temperature typically between 0 and 4 K depending on the region, and positive biases in specific humidity around 2–3 g kg−1 in tropical regions and negative biases around 1–2 g kg−1 farther south.
Particle Filtering in Geophysical Systems
Authors: van Leeuwen Peter Jan
Published: March 2009

The application of particle filters in geophysical systems is reviewed. Some background on Bayesian filtering is provided, and the existing methods are discussed. The emphasis is on the methodology, and not so much on the applications themselves. It is shown that direct application of the basic particle filter (i.e., importance sampling using the prior as the importance density) does not work in high-dimensional systems, but several variants are shown to have potential. Approximations to the full problem that try to keep some aspects of the particle filter beyond the Gaussian approximation are also presented and discussed.
Another Duel in the Sun: Weighing the Balances Between Sun Protection, Tanning Beds, and Malignant Melanoma
Authors: Roberts Daniel J. , Hornung Carlton A. , Polk Hiram C.
Published: March 2009

Objective. The purpose of this report is to put the dueling factors of risk and prevention for melanoma in perspective for the thoughtful pediatric specialist to facilitate preteen preventive health counseling. Study Design. We examined the rate of malignant melanoma among Kentucky residents and compared this rate with indicators of tanning bed prevalence in a large metropolitan area and sunscreen sales from a major distributor. We obtained malignant melanoma annual incidence data from the Kentucky Cancer Registry, which recorded Kentucky population incidence rates over the years 1995 to 2004. The rates reflected 2 malignant melanoma classifications: pre-invasive cancer only, or both invasive and noninvasive cancers combined. Results. The age-adjusted incidence rate per hundred thousand for combined invasive and pre-invasive malignant melanoma swelled from 21.9 in 1995 to 31.3 in 2004. The respective invasive-only malignant melanoma incidence rates increased less dramatically, from 17.3 to 20.7, during this same 10-year time period. Since 1983, the number of separate tanning bed businesses increased from 1 in 1983 to 119 by the mid-1990s, and then declined to about 74 separate businesses by 2003. Sunscreen sales data is uneven between states and is currently inconclusive. Conclusions. Although current data cannot draw a precise link between melanoma and the use of tanning beds, the associated risk is implicit, as the ultraviolet A (UVA) and ultraviolet B (UVB) radiation in tanning bed usage is a well-established melanoma risk factor. In advising patients, the pediatric specialist should consider that melanoma rates are poised as a balance of some known risk factors and a few potential preventive factors.
Interracial Roommate Relationships: Negotiating Daily Interactions
Authors: Trail Thomas E. , Shelton J. Nicole , West Tessa V.
Published: March 2009

Jobs, social group memberships, or living arrangements lead many people to interact every day with another person from a different racial background. Given that research has shown that interracial interactions are often stressful, it is important to know how these daily interactions unfold across time and what factors contribute to the success or failure of these interactions. Both members of same-race and mixed-race college roommate pairs completed daily questionnaires measuring their emotional experiences and their perceptions of their roommate. Results revealed that roommates in mixed-race dyads experienced less positive emotions and intimacy toward their roommates than did roommates in same-race dyads and that the experience of positive emotions declined over time for ethnic minority students with White roommates. Mediation analyses showed that the negative effects of roommate race were mediated by the level of intimacy-building behaviors performed by the roommate. Implications for future research and university policies are discussed.
Old-Age Wealth in Mexico
Authors: Wong Rebeca , DeGraff Deborah S.
Published: March 2009

The authors examined relationships between the wealth of older adults and their early-life decisions regarding investment in human capital, family formation, and work activities in Mexico, using the 2001 Mexican Health and Aging Study. The authors examined correlates of accumulated financial wealth by gender and across three age cohorts: 50 to 59, 60 to 69, and 70 years or older. The authors outline the changing context these cohorts experienced during their lifetimes; describe patterns of net financial worth by main covariates across groups defined by age, sex, and marital status; and present the results of multivariate models of net worth. Simulations were conducted to illustrate patterns of net worth associated with alternative scenarios depicting differing representative combinations of life-course characteristics by age cohort. The findings suggest that old-age financial wealth in Mexico is more closely associated with family formation and human capital decisions than with employment decisions over the lifetime.
Effects of antipsychotics and vitamin C on the formation of reactive oxygen species
Authors: Heiser P. , Sommer O. , Schmidt AJ , Clement HW , Hoinkes A. , Hopt UT , Schulz E. , Krieg JC , Dobschütz E.
Published: March 2009

There is evidence that reactive oxygen species (ROS) are involved in the pathophysiology of psychiatric disorders such as schizophrenia. Indirect biochemical alterations of ROS formation have been shown for patients treated with antipsychotics as well as for untreated patients. Only one study measured directly the ROS formation after treatment with antipsychotics by using electron spin resonance spectroscopy. The aim of the present examination was to demonstrate the effects of haloperidol, clozapine and olanzapine in concentrations of 18, 90 and 180 μg/mL on the formation of ROS in the whole blood of rats by using electron spin resonance spectroscopy after incubation for 30 min. To test the protective capacity of vitamin C we incubated the highest concentration of each drug with vitamin C (1 mM). Under all treatment conditions, olanzapine led to a significantly higher formation of ROS compared with control conditions, whereas in the cases of haloperidol and clozapine the two higher concentrations induced a significantly enhanced formation of ROS. Vitamin C reduced the ROS production of all drugs tested and for haloperidol and clozapine the level of significance was reached. Our study demonstrated that antipsychotics induce the formation of ROS in the whole blood of rats, which can be reduced by the application of vitamin C.
Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors
Authors: Thanos PK , Bermeo C. , Rubinstein M. , Suchland KL , Wang GJ , Grandy DK , Volkow ND
Published: March 2009

Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.
Effects of adjunctive reboxetine in patients with duloxetine-resistant depression: a 12-week prospective study
Authors: Seguí J. , López-Muñoz F. , Álamo C. , Camarasa X. , García-García P. , Pardo A.
Published: March 2009

The efficacy of the combination therapy with two antidepressants from different pharmacological families in patients with treatment-resistant depression has been reported in multiple studies. In this prospective 12-weeks open-label study, we assessed the effectiveness of the addition of reboxetine to 79 depressive outpatients diagnosed with major depressive disorder (MDD) according to the DSM-IV criteria who had previously not responded, or had done so only in a partial way, over 8 weeks of conventional treatment, in monotherapy, with duloxetine. Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Improvement (CGI-I). Safety was evaluated by recording spontaneously reported adverse events. Data were analysed on an intent-to-treat basis, using the last-observation-carried-forward method. Mean HDRS reduction was 65.5% (P < 0.0001). The percentages of responders (≥50% reduction in HDRS) and patients considered benefiting from complete remission (HDRS ≤ 10 points) at week 12 were 76% and 69.3%, respectively. By the end of the treatment, the score of CGI-I decreased 68.5% (P < 0.0001). Percentage of patient improving (CGI < 4 points) was 95.8%. The most common non-serious adverse events were dry mouth, increased sweating, constipation and difficulty passing urine. The results of this study suggest that the combination strategy with reboxetine may be an effective and well-tolerated tool in duloxetine-resistant patients.
An Applied Local Sustainable Energy Model
Authors: Hughes Kristen
Published: March 2009

Climate change is only one factor driving growing numbers of cities throughout the globe to reconsider conventional approaches to electricity generation and use. In the U.S., this momentum is incorporating a shift away from centralized, supply-side approaches reliant on fossil fuels and nuclear power, toward more distributed, flexible, and cleaner energy systems. In this regard, such systems entail elements of the emerging Sustainable Energy Utility (SEU) model enacted by the U.S. state of Delaware in 2007. The potential value of this model can be explored by examining those locales where elements of energy service compatible with an SEU have currently been adopted and implemented. This paper looks to one such community, Austin, Texas, to assess its utilization of an alternative energy pathway and the outcomes observed to date. Considered here are the technical, economic, and environmental dimensions of change, as well as the social dynamics accompanying new imperatives for energy development.
Relocating Energy in the Social Commons
Authors: Byrne John , Martinez Cecilia , Ruggero Colin
Published: March 2009

Climate change, rising energy costs, and other dilemmas raise the prospect for major change in energy-ecology-society relations. Two prominent proposals for change include: a nuclear power renaissance; and mega-scale renewable energy development. Both suggest that modern society will receive a rising stream of less CO2-rich kilowatt-hours, so that increased energy consumption and economic growth can continue. The article doubts these CO2 claims and finds both options lead to deepening unsustainability and environmental injustice. A third approach is proposed. A new institutional and community strategy called a Sustainability Energy Utility. The SEU looks to reduce energy use and seeks to support remaining energy needs by community-scale renewables. To accomplish deep energy change, the authors show how an SEU can move society from an energy commodity to energy commons regime. Commonwealth economy and community trusts are key means to significant change: a future commons is offered as the more appropriate strategy.