There was no association between troponin T levels as measured with the highly sensitive assay and the incidence of myocardial infarction (adjusted hazard ratio, 1.16; 95% CI, 0.97 to 1.40; P = 0.11).

CONCLUSIONS

After adjustment for other independent prognostic indicators, cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated Selleckchem Copanlisib with the incidence of cardiovascular death and heart failure but not with

myocardial infarction in patients with stable coronary artery disease.”
“A 56-year-old obese man with long-standing gastroesophageal reflux who recently received a diagnosis of Barrett’s esophagus presents for a follow-up visit. He has been taking omeprazole at a dose of 20 mg twice daily and currently has no symptoms of reflux. He has no dysphagia or weight loss. Endoscopic and histopathological examinations show a 4-cm segment of Barrett’s esophagus without

dysplasia. How should Barrett’s esophagus be managed?”
“Background Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes.

Methods We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural Vistusertib solubility dmso haematoma for burr-hole drainage were assessed for eligibility 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial

was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294).

Findings Doxacurium chloride Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups.

Interpretation Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months.

Funding Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).”
“Background A previous randomised controlled trial reported greater efficacy of surgery than of splinting for patients with carpal tunnel syndrome. Our aim was to compare surgical versus multi-modality, non-surgical treatment for patients with carpal tunnel syndrome without denervation.

Blood levels of BDE-47 in the dosed dams were within the range reported in humans. BDE-47 tissue levels in the dams decreased between parturition

and weaning, possibly reflecting mobilization during lactation. Brain BDE-47 levels in the offspring at PND 1 approached those of the dams at parturition. Perinatal exposure to BDE-47 resulted in significant dose dependent growth retardation, slower motor performance in several Repotrectinib behavioral tests, and mice exposed to 1 mg/kg/day BDE-47 showed altered performance in the Morris water maze. There were no differences between groups in the numbers of pyramidal neurons in hippocampus CM. These results document accumulation of BDE-47 in several organ systems following exposure to low-levels of BDE-47, and provide evidence that such exposure is associated with early behavioral deficits in exposed neonates. (C) 2011 Elsevier Inc. All rights reserved.”
“Estrogens have been shown to have a strong influence on such cognitive domains as spatial memory, response learning, and several tasks of executive function, including both working memory and attention. However, the effects of estrogens on inhibitory

control and timing behavior, both important aspects of executive function, have received relatively little attention. We examined the effects of estradiol on AR-13324 inhibitory control and timing behavior using a differential reinforcement of low rates

of responding (DRL) task Ovariectomized young (3 month), middle-aged (12 month), and old (18 month) Long-Evans rats were implanted with Silastic implants containing 0.5 or 10% 17 beta-estradiol in cholesterol vehicle and were tested on a DRL task requiring them to wait 15 s between lever presses to receive a food reinforcer. The ratio of reinforced to non-reinforced lever presses did not differ across age in the cholesterol vehicle group. Conversely, 17 beta-estradiol impaired learning of the DRL task in young and 3-oxoacyl-(acyl-carrier-protein) reductase middle-aged rats, but the learning of old rats was not impaired relative to vehicle controls following either 5% or 10% 17 beta-estradiol treatment. Overall, old rats also made fewer lever presses than both the young and middle-aged rats. These results provide new evidence that estrogens impair inhibitory control, an important aspect of self regulation, and add to existing evidence that estrogens differentially affect cognition at different ages. (C) 2011 Elsevier Inc. All rights reserved.”
“Paraquat (PQ) is an herbicide used extensively in agriculture. This agent is also suspected to be a risk factor for Parkinson’s disease (PD) by harming nigro-striatal dopamine neurons. There is likely, genetic-based, individual variability in susceptibility to PQ neurotoxicity related PD.

When adding the additional short-term GDC-0068 ic50 memory task, a larger and more bilateral frontoparietal network was recruited. We found enhanced activity during multitasking in components of the network that were already

involved in dual-tasking, suggesting increased working memory demands, as well as recruitment of multitask-specific components including areas that are likely to be involved in online holding of visual stimuli in short-term memory such as occipito-temporal cortex. These results confirm concurrent neural processing of a visual short-term memory task during dual-tasking and provide evidence for an effective fMRI multitasking paradigm. (C) 2013 Elsevier Ltd. All rights reserved.”
“Aim: Dysregulation of

the immune system may play a role in tic disorders. We screened for immune disturbances by investigating serum levels of cytokines and soluble adhesion molecules in patients with a tic disorder.

Methods: Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, soluble IL-2 receptor (sIL2R), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, soluble vascular cell adhesion molecule-1 (sVCAM-1), and intercellular adhesion molecule-1 (sICAM-1) of 66 children and adolescents with a tic disorder and 71 healthy volunteers were compared. We also addressed possible relations between concentrations of the immune markers and severity of tics and comorbid obsessive-compulsive Dehydrogenase inhibitor symptoms.

Results: Median serum concentrations did not differ significantly between patients and healthy subjects. Serum IL-2 concentrations were positively associated with tic severity ratings; serum IL-12 concentrations negatively with severity ratings of obsessive-compulsive symptoms.

Conclusions: These preliminary findings do not reveal major immune activation in children with a tic disorder but may suggest more subtle disturbances related to disease expression. (C) 2010 Elsevier Inc. All rights reserved.”
“Objective: In addition to increased risks for aneurysm-related death, previous

studies have determined that all-cause mortality in abdominal aortic aneurysm (AAA) patients is excessive and equivalent to that associated with coronary heart disease. These studies largely preceded the current era of coronary heart disease risk factor management, however, and no recent Sclareol study has examined contemporary mortality associated with early AAA disease (aneurysm diameter between 3 and 5 cm). As part of an ongoing natural history study of AAA, we report the mortality risk associated with presence of early disease.

Methods: Participants were recruited from three distinct health care systems in Northern California between 2006 and 2011. Aneurysm diameter, demographic information, comorbidities, medication history, and plasma for biomarker analysis were collected at study entry. Survival status was determined at follow-up.

These results suggest novel deficits in Fyn function, manifested as the downregulation selleckchem of Fyn protein or the altered transcription of the fyn gene, in patients with schizophrenia. (C) 2008 Elsevier Ireland Ltd. All fights reserved.”
“Intracerebral hemorrhage (ICH), accounting for 15-20% of strokes, can cause significant brain injury and life

long neurological deficits. We investigated whether treadmill exercise rehabilitation could improve brain repair after ICH and whether involvement of NFG-TrkA and BDNF-TrkB signaling could be observed during repair period in an experimental mouse ICH model reproduced by heparinized-collagenase infusion into the left caudate putamen. 5-Bromo-2-deoxyuridine (BrdU) labeled new dividing cell can be observed clearly around the injured cortex and striatum region on day 7 (D7) after operation, and both TrkA and TrkB neurotropic receptors were activated. A subgroup of these ICH mice began the treadmill exercise from D4 after operation. Then we found that the overall immunofluorescent signals of p-Y490-TrkA and p-Y705-TrkB were both decreased in all groups at 014 after

operation. However, compared to the non-exercise ICH group mouse, the immunofluorescent intensity of BDNF and p-Y705-TrkB were significantly AZD6094 higher in the exercise group. In addition, there was no difference in p-Y490-TrkA. Our results suggest that BDNF-TrkB but not NGF-TrkA signaling is involved in the brain repair after ICH, and early proper treadmill exercise might promote this repair process. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Failure to elicit broadly neutralizing (bNt) antibodies (Abs) against the membrane-proximal external region of HIV-1

gp41 (MPER) reflects the difficulty of mimicking its neutralization-competent structure (NCS). Here, we analyzed MPER antigenicity in the context of the plasma Levetiracetam membrane and identified a role for the gp41 transmembrane domain (TM) in exposing the epitopes of three bNt monoclonal Abs (MAbs) (2F5, 4E10, and Z13e1). We transiently expressed DNA constructs encoding gp41 ectodomain fragments fused to either the TM of the platelet-derived growth factor receptor (PDGFR) or the gp41 TM and cytoplasmic tail domain (CT). Constructs encoding the MPER tethered to the gp41 TM followed by a 27-residue CT fragment (MPER-TM1) produced optimal MAb binding. Critical binding residues for the three Nt MAbs were identified using a panel of 24 MPER-TM1 mutants bearing single amino acid substitutions in the MPER; many were previously shown to affect MAb-mediated viral neutralization. Moreover, non-Nt mutants of MAbs 2F5 and 4E10 exhibited a reduction in binding to MPER-TM1 and yet maintained binding to synthetic MPER peptides, indicating that MPER-TM1 better approximates the MPER NCS than peptides.

“
“The E1A gene of species C human adenovirus is an intensely investigated model viral oncogene that immortalizes primary cells and mediates oncogenic cell transformation in cooperation with other viral or cellular oncogenes. Investigations using E1A proteins have illuminated important paradigms in selleck chemical cell proliferation and about the functions of cellular proteins such as the retinoblastoma protein. Studies with E1A have led to the unexpected discovery that E1A also suppresses cell transformation and

oncogenesis. Here, I review our current understanding of the transforming and tumor-suppressive functions of E1A, and how E1A studies led to the discovery of a related tumor-suppressive function in benign human papillomaviruses. The potential role of these opposing functions in viral replication in epithelial cells is also discussed.”
“The tetrameric green fluorescent protein AsGFP(499) from the sea anemone Anemonia sulcata was converted into a dimeric and monomeric protein by site-directed Afatinib mutagenesis. The

protein was engineered without prior knowledge of its crystal structure based on a sequence alignment of multiple proteins belonging to the GFP-family. Crucial residues for oligomerisation of AsGFP(499) were predicted and selected for mutation. By introduction of a single site mutation (S103K) the A/B subunit was disrupted whereas two substitutions were necessary to separate the A/C subunit (T159K/F173E). This method can be applied as a general predictive method for designing monomeric proteins from multimeric fluorescent proteins. The maturation temperature was optimised to 37 degrees C by a combination of Site-directed

and random mutagenesis. In cell-based assays, the NFATc1A (nuclear factor of activated T-cells, subtype 1, isoform A)-AsGFP(499) chimera formed massive cytoplasmic aggregates in HeLa cells, which prevented the shuttling of NFATc1A into the nucleus and consequentially its transcriptional activity. In contrast, the cells expressing the NFATc1A in fusion with our engineered dimeric and monomeric fluorescent mutants were homogeneously distributed throughout the cytoplasm, making these stable cell lines functional in both translocation and transcriptonal assays. This new dual cellular assay will allow Oxalosuccinic acid the screening and discovery of new drugs that target NFAT cellular processes.”
“The pathophysiologic basis of hemifacial spasm is abnormal cross-transmission between facial nerve fibers. The author hypothesized that the demyelinated facial nerve fibers were connected with the sympathetic nerve fibers on the offending artery wall, and thus the latter function as a bridge in the cross-transmission circuit. This hypothesis was tested using a rat model of hemifacial spasm. A facial muscle response was recorded while the offending artery wall was electrically stimulated.

The illness left him severely weakened and unable to mount an aggressive campaign

to persuade the U. S. Senate of the importance of ratifying the Treaty of Versailles. His personal physician, Admiral Cary T. Grayson, stated that the President was mentally never the same after the sepsis.

Conclusions: Wilson’s voiding dysfunction contributed to his inability to win approval for the selleck screening library Treaty of Versailles and the League of Nations. As a result, the United States returned to a policy of isolationism and Europe plunged into 2 decades of upheaval, leading to World War II.”
“How does the brain carry out working memory storage, categorization, and voluntary performance of event sequences? The LIST PARSE neural model proposes an answer that unifies the explanation

of cognitive, neurophysiological, and anatomical data. It quantitatively simulates human cognitive data about immediate serial recall and free recall, and monkey neurophysiological data from the prefrontal cortex obtained during sequential sensory-motor imitation and planned performance. The model clarifies why spatial and non-spatial working memories share the same type of circuit design. It proposes how laminar circuits of lateral prefrontal cortex carry out working memory storage of event sequences within layers 6 and 4, how these event sequences are click here unitized through learning into list chunks within layer 2/3, and how these stored sequences can be recalled at variable rates that are under volitional control by the basal ganglia. These laminar prefrontal

circuits are variations of visual cortical circuits that explained data about how the brain sees. These examples from visual and prefrontal cortex illustrate how laminar neocortex can represent both spatial and temporal information, and open the way towards understanding how other behaviors derive from shared laminar neocortical designs.”
“In gray matter, cerebral endothelium is known to provide Molecular motor trophic support for neighboring cells such as neurons. However, signaling from cerebral endothelium to white matter cells remains to be elucidated. Here, we show that vascular endothelial growth factor (VEGF-A) secreted from cerebral endothelial cells promotes the migration but not the proliferation of oligodendrocyte precursor cells (OPCs). Cultured OPCs were obtained from newborn rat cortex, and treatment with conditioned culture media of cerebral endothelial cells increased the OPC proliferation and migration. Importantly, co-treatment with anti-neutralizing antibody for Flk-1 (VEGF-receptor2) inhibited OPC movement but did not affect OPC propagation. Western blot and flow cytometry analyses confirmed that our cultured cerebral endothelial cells produced VEGF-A and our cultured OPCs expressed Flk-1. Taken together, our current data suggest that cerebral endothelium is supportive for oligodendrocyte lineage cells and VEGF-A may participate in the endothelium-OPC cell-cell signaling.

(C) 2011 Elsevier Ltd. All rights reserved.”
“Objectives: Our objectives were (1) to determine whether elevated Mg(2+) in controlled hyperkalemic reperfusate without intervention during ischemia protects the juvenile heart against reperfusion injury; and (2) to identify the mechanism(s) underlying any protective effect of Mg(2+).

Methods: Langendorff-perfused

hearts from juvenile (11- to 14-day-old) guinea pigs were subjected to mild (30-minute) or severe (45-minute) learn more normothermic global ischemia and 35-minute reperfusion. Hearts were subjected to controlled hyperkalemic reperfusion without or with various concentrations of Mg(2+) (5, 10, 16, 23 mM). The mechanisms underlying the effect of Mg(2+) on intracellular Ca(2+) ([Ca(2+)] i) were also studied in isolated cardiomyocytes exposed to metabolic inhibition followed by washout using hyperkalemic solutions (reperfusion).

Results: Sixteen mM Mg(2+) conferred maximal cardioprotection as assessed by improved functional recovery and reduced cardiac injury; this was associated with a significant recovery of cardiac energetics and metabolism following both mild and severe ischemia. The Mg(2+)-induced protection was additive to that of hyperkalemia following mild ischemia and conferred protection following severe

ischemia when hyperkalemia alone had no significant effect. Elevated Mg(2+) in the hyperkalemic reperfusate of cardiomyocytes acutely prevented [Ca(2+)] i loading following mild metabolic inhibition and augmented the fall in [Ca(2+)] i following severe metabolic inhibition.

Conclusions: This work demonstrates for selleck compound the first time in juvenile hearts that elevated Mg(2+) during controlled hyperkalemic reperfusion rescues the heart following ischemia, and that this is likely to be facilitated

by reducing [Ca(2+)] i which, in turn, would aid metabolic recovery. (J Thorac Cardiovasc /www.selleck.co.jp/products/MG132.html Surg 2011;141:1529-37)”
“The present report describes a case of a 33-year old male patient with homozygous sickle cell disease (SCD) with comorbid psychotic symptoms. The systematical evaluation revealed an intimate association between acute SCD complications, associated with hematological abnormalities, and psychotic symptoms worsening. Clozapine was effective in controlling psychotic symptoms refractory to previous antipsychotic trials. (c) 2007 Elsevier Inc. All rights reserved.”
“Melatonin, a ubiquitous methoxyindole, is produced by and metabolized in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cells. Melatonin has both receptor-dependent and receptor-independent effects that protect against oxidative stress and can attenuate ultraviolet radiation-induced damage. The widespread expression and pleiotropic activity of the cutaneous melatoninergic system provides for a high level of cell-specific selectivity.

(C) 2009 Elsevier Ltd. All rights reserved.”
“Kaposi’s sarcoma-associated herpesvirus (KSHV) utilizes clathrin-mediated endocytosis for selleck its infectious entry into human foreskin fibroblast (HFF) cells (S. M. Akula, P. P. Naranatt, N.-S. Walia, F.-Z. Wang, B. Fegley, and B. Chandran, J. Virol. 77: 7978-7990, 2003). Here,

we characterized KSHV entry into primary human microvascular dermal endothelial (HMVEC-d) and human umbilical vein endothelial (HUVEC) cells. Similar to the results for HMVEC-d cells, KSHV infection of HUVEC cells also resulted in an initial high level and subsequent decline in the expression of the lytic switch gene, ORF50, while latent gene expression persisted. Internalized virus particles enclosed in irregular vesicles were observed by electron microscopy of infected HMVEC-d cells. At an early time of infection, colocalization of KSHV capsid with envelope was observed by immunofluorescence analysis, thus demonstrating endocytosis of intact enveloped virus

particles. Chlorpromazine, an inhibitor of clathrin-mediated endocytosis, and filipin (C(35)H(58)O(11)), a caveolar endocytosis inhibitor, did not have any effect on KSHV binding, entry (DNA internalization), or gene expression in HMVEC-d and HUVEC cells. In contrast to the results for HFF cells, virus entry and gene expression in both types of endothelial cells were significantly

blocked by macropinocytosis inhibitors (EIPA [5-N-ethyl-N-isoproamiloride] mTOR inhibitor and rottlerin [C(30)H(28)O(8)]) and by cytochalasin D, which affects actin polymerization. Inhibition of selleck compound lipid raft blocked viral gene expression in HMVEC-d cells but not in HUVEC or HFF cells. In HMVEC-d and HUVEC cells, KSHV induced the actin polymerization and formation of lamellipodial extensions that are essential for macropinocytosis. Inhibition of macropinocytosis resulted in the distribution of viral capsids at the HMVEC-d cell periphery, and capsids did not associate with microtubules involved in the nuclear delivery of viral DNA. Internalized KSHV in HMVEC-d and HUVEC cells colocalized with the macropinocytosis marker dextran and not with the clathrin pathway marker transferrin or with caveolin. Dynasore, an inhibitor of dynamin, did not block viral entry into endothelial cells but did inhibit entry into HFF cells. KSHV was not associated with the early endosome marker EEA-1 in HMVEC-d cells, but rather with the late endosome marker LAMP1, as well as with Rab34 GTPase that is known to regulate macropinocytosis. Silencing Rab34 with small interfering RNA dramatically inhibited KSHV gene expression. Bafilomycin-mediated disruption of endosomal acidification inhibited viral gene expression.

Urologists can use this nomogram to better inform patients of the potential need for epididymovasostomy and whether specialist referral is needed.”
“The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (H-1-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on

expression of ERBB4 in the hippocampus and dorsolateral this website prefrontal cortex in human post mortem tissue. Our aim was to examine the association of rs7598440 with cerebrospinal fluid (CSF) GABA levels in healthy volunteers (n = 155). We detected a significant selleck chemical dose-dependent association of the rs7598440 genotype with CSF GABA levels (G-allele standardized beta = -0.23; 95% CIs: -0.39 to -0.07; P=0.0066). GABA concentrations were highest in A homozygous, intermediate in heterozygous, and lowest in G homozygous subjects. When excluding subjects on psychotropic medication (three subjects using antidepressants), the results did not change (G-allele standardized beta=-0.23; 95% CIs: -0.40

to -0.07; P=0.0051). The explained variance in CSF GABA by rs7598440 in our model is 5.2% (P=0.004). The directionality of our findings agrees with the aforementioned H-1-MRS and gene expression studies. Our observation therefore strengthens the evidence that the A-allele of rs7598440 in ERBB4 is associated with increased GABA concentrations in the human central nervous Unoprostone system (CNS). To our knowledge, our finding constitutes the first confirmation that CSF can be used to study genotype-phenotype correlations of GABA levels in the CNS. Such quantitative genetic analyses may be extrapolated to other CSF constituents relevant to SCZ in future studies. Neuropsychopharmacology (2012) 37, 2088-2092; doi:10.1038/npp.2012.57; published online

2 May 2012″
“Nanomedicine, or medicine using nanometric devices, has emerged in the past decade as an exhilarating domain that can help to solve a number of problems linked to unsatisfactory therapeutic responses of so-called ‘old drugs’. This dissatisfaction stems from inadequate biodistribution after a drug’s application, which leads to a limited therapeutic response but also to numerous side effects to healthy organs. The biodistribution of drugs encapsulated in a nanoobject that will act as a vector can be modified to tune its therapeutic efficacy. This review provides a general overview of existing colloidal nanovectors: liposomes, polymeric micelles, polymeric vesicles, polymeric nanoparticles (NPs), and dendrimers. We describe their characteristics, advantages and drawbacks, and discuss their use in the treatment of various diseases.

Our results revealed densely packed DCX-positive cells in the entire extent of the subventricular zone from where cells migrated along the rostral migratory stream to the olfactory bulb. In the olfactory bulb, DCX-expressing cells were primarily present in the granular Compound C mw cell layer with radially orientated dendrites and in

the glomerular layer representing periglomerular cells. In the hippocampus, DCX-positive cells were identified in the subgranular and granular layers of the dentate gyrus and strongly labelled DCX-positive processes, presumably dendrites and axons of the newly generated granular cells, were observed in the CA3 regions. In addition, DCX immunoreactive cells were present in the olfactory tubercle, the piriform cortex and the endopiriform nucleus. While DCX-positive fibres have been previously observed in the anterior commissure of the hedgehog and mole, we were able to demonstrate

the presence Selleckchem GANT61 of DCX-positive cells presumably migrating across the anterior commissure. Taken together, the giant otter shrew reveals patterns of neurogenesis similar to that seen in other mammals; however, the appearance of possible neuronal precursor cells in the anterior commissure is a novel observation. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The HIV pandemic represents a major source of neurological morbidity worldwide. Emerging data from diverse populations indicate that HIV leads to significant neurocognitive impairments that reduce individuals’ ability to contribute to the well being of their families and society. HIV affects vulnerable populations with many comorbidities, but the virus contributes to neurocognitive impairment independent of these conditions. The neuropathological

substrate of HIV neurocognitive disorders is damage to synapses Epothilone B (EPO906, Patupilone) and dendrites, without major neuronal loss. This suggests the potential for substantial reversibility if synaptodendritic function can be restored. In the developed world, combination antiretroviral therapy (CART) leads to improved neurocognitive function as well as morbidity and mortality in HIV. CART is being used in increasing numbers of individuals in resource limited settings. New cases of severe dementia are now rare in populations where effective CART has been deployed. While some degree of neurocognitive improvement with CART is almost universal, many individuals do not achieve full restoration of their premorbid neurocognitive status, and milder degrees of impairment remain quite prevalent. Optimizing neurocognitive recovery is likely to require the development of better CNS penetrating antiretroviral regimens and the use of neuroprotective agents. (C) 2009 Elsevier Ltd. All rights reserved.