text:
These authors contributed equally to this work.
Liver Failure/Cirrhosis/Portal Hypertension
Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis†
Article first published online: 20 NOV 2009
DOI: 10.1002/hep.23440
Copyright © 2010 American Association for the Study of Liver Diseases
Additional Information
How to Cite
Appenrodt, B., Grünhage, F., Gentemann, M. G., Thyssen, L., Sauerbruch, T. and Lammert, F. (2010), Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis. Hepatology, 51: 1327–1333. doi: 10.1002/hep.23440
- †
Potential conflict of interest: Nothing to report.
Publication History
- Issue published online: 26 MAR 2010
- Article first published online: 20 NOV 2009
- Accepted manuscript online: 20 NOV 2009 12:00AM EST
- Manuscript Accepted: 10 NOV 2009
- Manuscript Received: 19 AUG 2009
Funded by
- University of Bonn. Grant Number: BONFOR O-107.0083
- Dr. Robert Pfleger Foundation, Bamberg, Germany
- Deutsche Forschungsgemeinschaft. Grant Number: SFB/TRR 57 TP01 tp F.L.
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
Spontaneous bacterial peritonitis (SBP), a severe complication in patients with advanced liver cirrhosis, has been attributed to bacterial translocation from the intestine. Variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene have been associated with impaired mucosal barrier function in Crohn disease. We hypothesized that the risk of acquiring SBP is increased in patients with cirrhosis carrying NOD2 variants. We recruited 150 nonselected patients with liver cirrhosis and ascites admitted to our unit, monitored survival, and recorded the development of SBP prospectively and retrospectively. SBP was defined as the presence of polymorphonuclear neutrophil (PMN) cells >250 per μL of ascitic fluid. Patients were genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. During a median follow-up of 155 days, 54 patients (36%) died and SBP was diagnosed in 30 patients (20%). The occurrence of SBP was increased significantly (P = 0.008) in carriers of NOD2 variants (odds ratio [OR] = 3.06). Retrospectively, SBP was observed in 22 additional patients, and the combined prospective and retrospective analysis substantiated the association between NOD2 and SBP (P = 0.004; OR = 2.98). Of note, carriers of NOD2 risk alleles showed a significantly (P = 0.007) reduced mean survival time (274 days) in comparison to patients with wildtype genotypes (395 days). Conclusion: Common NOD2 variants linked previously to impaired mucosal barrier function may be genetic risk factors for death and SBP. These findings might serve to identify patients with cirrhotic ascites eligible for preemptive antibiotic treatment. (HEPATOLOGY 2010.)
Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhosis. As a marker of severe hepatic dysfunction, SBP occurs in up to 30% of patients with cirrhosis and ascites.1 The survival of patients with liver cirrhosis who recover from a first episode of SBP is significantly reduced and despite antibiotic treatment, SBP is still associated with in-hospital mortality rates between 15% and 30%.2–4 The term SBP was coined more than 40 years ago by Conn,5, 6 who speculated that the translocation of intestinal bacteria represents a critical event in the development of SBP. However, genetic factors predisposing to bacterial translocation and SBP have not been identified to date. It has long been anticipated that in addition to intestinal bacterial overgrowth and immune dysfunction, patients at risk for SBP demonstrate increased intestinal permeability, a prerequisite for bacterial translocation from the gut,7–9 which is defined as the migration of bacteria from the intestinal lumen to mesenteric lymph nodes or other extraintestinal sites.4
In 2001, variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene (Supporting Fig.) were associated with impaired mucosal barrier function in Crohn disease.10–12 Because NOD2 is involved in the intestinal recognition of bacteria and bacterial products, insufficient activation of NF-κB in carriers of NOD2 risk variants may result in deficient elimination of bacteria and enhancement of their translocation from the intestine.13 It has also been shown that NOD2 variants influence survival in sepsis14 and graft-versus-host disease (GvHD),15 but there is no evidence for a correlation with any liver disease. We hypothesized that the development of SBP in patients with liver cirrhosis is also associated with NOD2 risk variants. The aim of the present study was to assess the potential role of NOD2 as a gene conferring susceptibility to SBP or even death in a large series of patients with cirrhosis and advanced liver cirrhosis and ascites. For the study, we selected those three NOD2 variants (p.R702W, pG908R, and c.3020insC; Supporting Fig.) that are known to confer a deficit in NF-κB activation in response to lipopolysaccharide and peptidoglycan,16 providing evidence for a unifying pathomechanism whereby NOD2 variants confer an increased risk for complications of liver cirrhosis.
Patients and Methods
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
Patient Cohort.
Between May 2006 and October 2007 we prospectively recruited 150 patients with liver cirrhosis and ascites who were admitted for hospitalization to the Department of Internal Medicine I, University Hospital Bonn, Germany. Criteria for inclusion were liver cirrhosis and ascites detected by ultrasound. Cirrhosis was diagnosed by clinical, laboratory, and ultrasound findings, or histology if available (fibrosis stage 4). All patients were of Caucasian ethnicity. The severity of the underlying liver disease was assessed according to the Model of End-stage Liver Disease (MELD) and the Child-Pugh score.
The recruitment of the patients was approved by the human research ethics committee of the Medical Faculty at the University of Bonn, and all patients provided informed consent for inclusion in the study. After informed consent, we obtained EDTA-anticoagulated blood and serum samples for standard hematological, biochemical and coagulation tests, and performed the index paracentesis. Ascites was analyzed for the following parameters: total and differential cell counts, total protein and albumin concentrations, pH, glucose and cholesterol levels as well as lactic acid dehydrogenase activity according to standard operational procedures of the clinical chemical laboratory. Ascitic cytology for differential white blood and polymorphonuclear neutrophil (PMN) cell counts was performed on a stained smear made from the sediment of 10 mL centrifuged ascitic fluid.17
Following the criteria of the International Ascites Club,1 SBP was diagnosed when the ascites PMN cell count was >250/μL. During the current and subsequent hospital stays, we monitored the occurrence of SBP and causes of death. Following the consensus criteria for the systemic inflammatory response syndrome (SIRS),18 SIRS was diagnosed retrospectively when at least two of the following criteria were present: temperature <36°C or >38°C, heart rate >90 bpm, and white blood cell (WBC) count <4,000/mm3 or >12,000/mm3; because patients were admitted on our general wards without monitoring respiratory rates or PaCO2, these SIRS criteria could not be considered. In addition, we recorded treatment with antibiotics at the time of admission to our unit. Furthermore, we analyzed the patients' medical history in our hospital and identified previous SBP episodes as defined above.
Bacterial (bact) DNA in ascitic fluid was identified by a multiplex real-time polymerase chain reaction (PCR)-based assay for rapid detection and simultaneous automated differentiation of bactDNA (LightCycler SeptiFast Mgrade, Roche Diagnostics, Mannheim, Germany) employing a protocol validated at our institution and published recently.30, 31
All patients were followed until death, liver transplantation, or the end of our observation period 3 months after the inclusion of the last patient. The median follow-up time was 114 days (range 1-575). Patients receiving liver transplantation were censored on the day of transplantation.
Genomic DNA was extracted from EDTA-anticoagulated blood using a membrane-based extraction kit (Qiagen, Hilden, Germany). DNA concentration was calibrated to 5-20 ng/μL, using a NanoDrop ND-1000 spectrophotometer (Peqlab, Erlangen, Germany).
The NOD2 gene variants (rs2066844 [p.R702W], rs2066845 [p.G908R], rs2066847 [c.3020insC]; Supporting Fig.) were genotyped using solution-phase hybridization reactions with 5′-nuclease and fluorescence detection (TaqMan assays) on the 7300 Real-Time PCR System (Applera, Norwalk, CT). PCR reactions contained 20 ng genomic DNA, 1× Platinum qPCR SuperMix-UDG master mix (Invitrogen, Karlsruhe, Germany) 900 nM of each primer, and 200 nM of VIC-labeled and FAM-labeled probes, respectively, in 25-μL reactions. Amplification conditions were 95°C for 10 minutes, followed by 45 cycles at 95°C for 15 seconds and 60°C for 60 seconds. Primer and probe sequences were: p.R702W, MGB_F CTGAGTGCCAGACATCTGAGAAG, MGB_R GCTGCGGGCCAGACA, VIC CCTGCTCTGGCGCC, FAM CTGCTCCGGCGCC; p.G908R, MGB_F TGATCACCCAAGGCTTCAGC; MGB_R GAACACATATCAGGTACTCACTGACAC; VIC ACTCTGTTGCG- CCAGA; FAM CTGTTGCCCCAGAAT; c.3020insC, MGB_F CCAGGTTGTCCAATAACTGCATC; MGB_R CCTTACCAGACTTCCAGGATGGT; VIC TGCAGGCCCCTTG; FAM CTGCAGGCCCTTG. Selected results of TaqMan assays were ascertained by direct BigDye termination cycle sequencing on the ABI PRISM 310 Genetic Analyzer (Applera).
Statistical Analysis.
Statistical analysis was performed with SPSS 13.0 (SPSS, Munich, Germany). Data are given as medians and ranges.
Differences of survival between carriers of different genotypes were analyzed by Kaplan-Meier statistics (log-rank test). To test for independence of risk factors on survival, we performed multivariate regression analysis. Candidate variables that entered the univariate analysis were age, gender, serum albumin, serum bilirubin, platelet count, serum creatinine, total protein in serum, MELD score, the presence of any NOD2 risk allele, and SBP. Significant univariate risk factors entered the multivariate regression analysis, which was performed with an incrementally forward stepwise approach. Probabilities were set at 0.05.
An exact test was used to check whether genotype frequencies are consistent with Hardy-Weinberg equilibrium, indicating that alleles are distributed by random mating and remain constant in the given population. Allele and genotype frequencies were compared between cases and controls by Pearson's goodness-of-fit χ2 test and Armitage's trend test, respectively (http://ihg.gsf.de/ihg/snps.html).
Power calculations were performed using PS (http://biostat.mc.vanderbilt.edu/wiki/Main/PowerSampeSize). We calculated that the study was designed to detect a significantly increased odds ratio (OR) of 2 with a power of 80%, based on risk allele frequencies of 0.10 and type I error rates of 0.05. For the survival analysis, the study had a power of 99%, given an expected mortality rate of 30% that we expected on the basis of our previous study with comparable patients.19
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
Patient Characteristics and SBP Frequency.
Table 1 illustrates that the majority of our patients presented with ascites due to alcoholic liver cirrhosis (63%) or chronic viral hepatitis (17%). All other etiologies were less common. Most patients were males (72%), and the median age of all patients was 57 years (range 23–86). As expected, the majority of patients showed advanced liver disease, with 94% of the patients classifying for Child-Pugh scores B or C. The median MELD score at the time of admission was 16 (range 5–40). C-reactive protein levels at the time of paracentesis did not differ between patients with NOD2 risk alleles (29 ± 31 mg/dL) variants and those without (28 ± 30 mg/dL).
Total Number | 150 |
| |
Median age years (range) | 57 (23 – 86) |
Gender (male/female) | 108/42 |
Etiology of cirrhosis n (%) | |
Alcoholic | 94 (62.7) |
Chronic hepatitis B/C virus infection | 26 (17.3) |
Autoimmune hepatitis, chronic cholestatic | 13 (8.7) |
liver diseases and vascular diseases | |
Hemochromatosis | 2 (1.3) |
α1-Antitrypsin deficiency | 2 (1.3) |
Cryptogenic liver cirrhosis | 13 (8.7) |
Median INR (range) | 1.3 (0.9 – 4.7) |
Median total serum bilirubin mg/dL (range) | 2.03 (0.24 – 38.79) |
Median serum creatinine mg/dL (range) | 1.31 (0.38 – 14.93) |
Median MELD score (range) | 16 (5 – 43) |
Child-Pugh score n (%) | |
Antibiotic treatment at time of admission | |
n (% of total) | 46 (30.7) |
– Quinolone | 30 (20.0) |
– Ampicilline | 10 (6.7) |
– Cephalosporin | 4 (2.7) |
– Metronidazole | 2 (1.3) |
Employing PMN cell count >250/μL as a diagnostic criterion, 14 patients (9% of the cohort) were diagnosed with SBP on the first day of admission (index paracentesis), 16 patients (11%) in the follow-up period (median 155 days, range 1–575), and 22 patients (15%) during previous hospital stays.
NOD2 Risk Variants Negatively Affect Survival.
For the survival analysis, patients who were lost to follow-up (n = 2) were excluded and patients who received a liver transplant (n = 7) were right-censored. In total, 54 patients (36%) died. Table 2 summarizes the causes of death for these patients, with acute-on-chronic liver failure and infections representing the most common conditions.
Causes | n (%) |
| |
Acute-on-chronic liver failure | 26 (48.1) |
Infections/SIRS | 9 (16.7) |
Hepatorenal syndrome | 8 (14.8) |
Gastrointestinal hemorrhage | 3 (5.6) |
Not specified | 8 (14.8) |
Total number of deaths | 54 (100.0) |
Table 3 summarizes the minor allele frequencies for the three NOD2 variants in the different groups of patients, all of which were in the range or slightly above previously reported frequencies in Caucasian healthy cohorts.20 No patients carried homozygous NOD2 mutations. The NOD2 genotype distributions in the total cohort were consistent with Hardy-Weinberg equilibrium (all P > 0.05). In our cohort, 19 patients carried the variant p.R702W, 10 carried p.G908R, and eight tested positive for c.3020insC (Supporting Fig.).
Minor Allele Frequencies of NOD2 Variants (%) | |||
p.R702W | p.G908R | c.3020insC | |
| |||
Total cohort | 6.3 | 3.3 | 2.7 |
PMN > 250/uL | 8.7 | 5.8 | 4.8 |
PMN < 250/uL | 5.1 | 2.0 | 1.5 |
Figure 1 demonstrates that patients who tested positive for any of the NOD2 risk alleles showed a significantly (P = 0.007, log-rank test) reduced survival in comparison to patients with wildtype genotypes at all three positions. The mean survival time in patients who carried any NOD2 risk allele was 274 days in comparison to 395 days in patients who carried wildtype genotypes.
By univariate analysis, we demonstrated that carrier status for any NOD2 risk allele, male gender, MELD score, the development of SBP, and serum albumin were risk factors for death (all P < 0.05), whereas age or other risk indicators (platelet count, serum bilirubin, serum creatinine, total protein) were not (Table 4A). Multivariate regression analysis demonstrated that the detection of any NOD2 risk variant was the strongest independent predictor of death with an OR of 4.32 (Table 4B).
(A) Univariate Analysis | ||||
Parameter | OR | 95% CI | P | |
Lower | Upper | |||
| ||||
Age | 0.67 | |||
Albumin | 0.94 | 0.89 | 0.99 | 0.020 |
Male gender | 2.65 | 1.15 | 6.11 | 0.022 |
MELD score | 1.05 | 1.01 | 1.11 | 0.029 |
NOD2 risk allele | 3.88 | 1.78 | 8.46 | 0.001 |
(B) Multivariate Analysisa | ||||
Parameter | OR | 95% CI | P | |
Lower | Upper | |||
MELD score | 1.78 | 1.02 | 1.14 | 0.005 |
NOD2 risk allele | 4.32 | 1.82 | 10.25 | 0.001 |
Overall, eight (5.3%) patients fulfilled the criteria of SIRS at time of admission. Of these, three patients had NOD2 risk variants, and five patients carried no NOD2 variants. During follow-up, nine patients died due to SIRS (Table 2; four patients with and five patients without NOD2 variants).
NOD2 Risk Variants Are Associated with SBP.
Table 5A demonstrates that patients carrying a risk allele of any of the three NOD2 variants developed SBP, defined as PMN cell count >250/μL, more frequently at index paracentesis or during follow-up (OR = 3.06, 95% confidence interval [CI] = 1.31–7.15, P = 0.008). In addition to these 30 patients (Table 5A), SBP was documented in 22 additional patients before inclusion in the study. Table 5B shows that the combined prospective and retrospective analysis of both groups together substantiated the association between NOD2 and SBP and indicated a similarly increased risk of SBP (OR = 2.98; 95% CI = 1.39–6.40, P = 0.004). Although the risk allele frequencies of all NOD2 variants tended to be higher in patients with SBP (Table 3), no statistically significant differences were observed for individual NOD2 SNPs.
(A) Prospective Analysis | |||
SBP (PMN >250/μL) | No SBP (PMN <250/μL) | P (χ2 test) | |
| |||
NOD2 risk allele | 13 | 24 | 0.008 |
No NOD2 risk allele | 17 | 96 | OR = 3.06 (95% CI 1.31–7.15) |
(B) Prospective and Retrospective Analysis | |||
SBP (PMN >250/μL) | No SBP (PMN <250/μL) | P (χ2 test) | |
NOD2 risk allele | 20 | 17 | 0.004 |
No NOD2 risk allele | 32 | 81 | OR = 2.98(95% CI 1.39–6.40) |
In ascites samples from 15 patients (10%), we detected bactDNA, and four of these patients carried NOD2 risk alleles. However, contingency table analysis did not support an association between NOD2 genotypes and the presence of bactDNA.
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
In this study we report a significant association of SBP with common risk variants of the NOD2 gene in patients with advanced liver cirrhosis and ascites. Importantly, the study demonstrates that the NOD2 variants confer a substantially increased risk for death in patients with cirrhosis.
Increased bacterial translocation in cirrhosis has been attributed to structural changes of the intestinal mucosa including dilatation of intercellular space and vascular congestion as well as mucosal oxidative damage.4, 8, 21 Furthermore, innate and adaptive immune responses normally limit the penetration of bacteria across the epithelium, but activation and transmigration of PMN cells cause the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) as well as nitric oxide, all of which modulate bacterial translocation.4, 8, 9, 22 In the present study we identified NOD2 variants as novel inherited risk factors for SBP in liver cirrhosis. In our prospective analysis, the OR for SBP was about 3 (Table 5A), and this high ratio is in the range of other disease risks conferred by the NOD2 variants.10, 23 Although the results were corroborated by the combined prospective and retrospective analysis that took both occurrence of SPB during follow-up and previous history of SBP into account and resulted in a similar OR (Table 5B), our study warrants further evaluation and needs to be replicated in an independent population. Because about a third of the patients received antibiotics on admission (Table 1), it is likely that we underestimated the frequency of SBP and biased the result against genetic effects.
The genetic study indicates that the local immune system in carriers of the NOD2 variants may be incapable of limiting bacterial translocation from the intestine. NOD2 is expressed in intestinal epithelial and mononuclear cells and represents an intracellular "pattern recognition receptor" that senses the muramyl dipeptide component of bacterial cell walls and leads to activation of the proinflammatory NF-κB signaling pathway.13, 24 The NOD2 risk variants associated with Crohn disease reduce the ability of NOD2 to activate NF-κB25, and a decrease in NF-κB-induced inflammatory response and intestinal production of antimicrobial peptides such as α-defensins26 may favor bacterial translocation and systemic inflammation. Consistent with this paradigm, the NOD2 risk variants might also be associated with gastrointestinal GvHD after allogeneic stem cell transplantation, another condition with increased bacterial translocation.15 The presence of bacterial DNA (bactDNA) in blood was reported in 40% of patients with cirrhosis and considered to be evidence of bacterial translocation.27, 28 Recently, the presence of bactDNA in blood and ascitic fluid was shown to define subgroups of patients with poor prognosis, with acute-on-chronic liver failure representing the most common cause of death.22, 29 Using a multiplex real-time PCR-based assay for rapid detection and differentiation of bactDNA validated recently by us and other groups,30, 31 we did not detect an association between NOD2 variants and the presence of bactDNA in ascites.32 However, these data have to be compared to ascites analyses based on other DNA tests,21, 26, 27 and it has yet to be resolved whether bactDNA represents a reliable surrogate marker for local and/or systemic infection in patients with cirrhosis.
In the present study the three NOD2 variants were plainly associated with risk of death in our patients with advanced cirrhosis (OR 4.3), with acute-on-chronic failure again being the most frequent cause of death (Table 2). Accordingly, we note that the NOD2 variants might impair survival not only by impaired mucosal barrier function but by extraintestinal mechanisms, because NOD2 is also expressed in hepatocytes and immune cells in liver, stimulating cellular responses to muramyl dipeptide and hepatic IFN-γ and NF-κB signaling.33 As highlighted above, the NOD2 variants have been linked to mortality in GvHD, partially explained by pulmonary failure,15 and in sepsis,14 a frequent cause of death in patients with advanced cirrhosis.34 SIRS is associated with poor in-hospital outcome in patients with advanced cirrhosis,35 and in the present study the frequency of NOD2 risk alleles tended to be higher in patients with SIRS as compared to the total cohort, but the small number of SIRS patients precluded statistical analysis.
Because survival rates of SBP have improved in recent years, prevention has come into focus, in particular in patients who do not yet meet the conventional criteria for increased SBP risk, such as a previous episode of SBP, gastrointestinal hemorrhage, or low ascites protein levels.1, 9, 36 Recently a randomized study that included patients with low ascites protein concentrations37 and a meta-analysis38 have indicated that antibiotic prophylaxis reduces SBP occurrence and improves short-term survival in high-risk patients with cirrhosis and ascites. Reducing the bacterial load in the gut by selective intestinal decontamination decreases the frequency of SBP, but increases the risks for infections with antibiotic-resistant bacteria39, 40 or posttransplant fungal infections41; thus, prophylaxis is currently restricted to patients at highest risk of SBP, as defined above.9 Now that we might have identified a new subpopulation of patients with cirrhosis at high risk for both SBP and death, this clearly sets the stage for a prospective study of primary prophylaxis of SBP to see whether long-term survival can be further improved in genetically defined at-risk patients.
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
The authors thank all patients for participating in this study and providing blood samples, and Stephanie Schwartz and Hildegard Keppeler for excellent technical assistance. Contributions: B.A. and F.G. contributed equally to data acquisition and analysis. M.G. and L.T. helped in study design, collected data and recruited patients as part of their doctoral theses. T.S. and F.L. were responsible for study concept, design, and supervision. B.A. and F.G. drafted the article, which was edited by T.S. and F.L. This study was presented in part as Presidential Poster of Distinction at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), San Francisco, November 4, 2008, and published in abstract form (HEPATOLOGY 2008;48:A1676).
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
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- 2Survival after a first episode of spontaneous bacterial peritonitis. Prognosis of potential candidates for orthotopic liver transplantation. J Gastroenterol Hepatol 1995; 10: 47–50., , , , , , et al.
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- 10Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001; 411: 599–603., , , , , , et al.
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- 15Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 2004; 104: 889–894., , , , , , et al.
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- 17Total ascitic fluid leukocyte count for reliable exclusion of spontaneous bacterial peritonitis in patients with ascites. Eur J Gastroenterol Hepatol 2006; 18: 181–186., , , , .
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- 24Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem 2003; 278: 5509–5512., , , , , , et al.
- 25New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat Rev Genet 2008; 9: 9–14..
- 26NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 2004; 53: 1658–1664., , , , , , et al.
- 27A sequential study of serum bacterial DNA in patients with advanced cirrhosis and ascites. HEPATOLOGY 2004; 39: 484–491., , , , , , et al.
- 28Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. HEPATOLOGY 2002; 36: 135–141., , , , , , et al.
- 29Identification of bacterial DNA in neutrocytic and non-neutrocytic cirrhotic ascites by means of a multiplex polymerase chain reaction. Liver Int 2009; 29: 1206–1214., , , , , , et al.
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- 31Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia. J Clin Microbiol 2009; 47: 2405–2410., , , , , , et al.
- 32Detection of bacterial DNA in ascites in patients with liver cirrhosis: is it prognostic relevant or an epiphenomenon? [Abstract] HEPATOLOGY 2008; 48(Suppl): A1729., , , , , , et al.
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Supporting Information
- Top of page
- Abstract
- Patients and Methods
- Results
- Discussion
- Acknowledgements
- References
- Supporting Information
Additional Supporting Information may be found in the online version of this article.
Filename | Format | Size | Description |
HEP_23440_sm_SupFig1.tif | 64K | Supporting Figure 1 Schematic diagram of the genomic structure of the NOD2 gene, the location of the variants studied, and the predicted structural domains of the encoded protein. The three variants p.R702W, p.G908R and c.3020insC are all located within or near the leucine-rich repeats (LRRs) of NOD2. The LRR domain is located at the C-terminus and represents the major structural motif that functions as pattern recognition receptor for broad types of bacterial components. Adapted from: Bonen DK, Cho JH. Gastroenterology 2003;124:521-536. Abbreviations: CARD, caspase recruitment domain; NBD, nucleotide binding domain; LRR, leucine-rich repeat; p, protein (amino acid number). | |
SupportingTable1.pdf | 47K | Supporting Table 1. Numbers of carriers of any NOD2 risk allele in cirrhotic patients with and without bactDNA |
Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.


text:
Thanks, Jeff! Do you know if Henry Jacob Spindler was an early immigrant? If so, where? Where did Geo.Friedrich Spindler live? There is a Geo.Friedrich in the family of Geo.Jacob Spindler and wife Maria Eliz. in Baltimore Co.MD. Wonder if there's a connection?
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subset: commoncrawl


text:
Samuel v US 563148 A Abstract available in Claims available in Description (OCR text may contain errors) (No Model.) S. V. ESSIGK. TELEGRAPH ALPHABET. M No. 563,148. Patented June 30,1896. B s- T u v L 4. L e WITNESSES: 5%! Z INVENTOR UNITED STATES PATENT OFFICE. SAMUEL V. ESSICK, OF YONKERS, NEIV YORK. TELEGRAPH-ALPHABET. SPECIFICATION forming part of Letters Patent No. 563,148, dated June 30, 1896. Application filed September 16, 1895. T 0 aZZ whom it may concern.- Be it known that I, SAMUEL V. EssIcK, a citizen of the United States, and a resident of Yonkers, in the State of New York, have invented a new and useful Improvement in Telegraph-Alphabets, of which the following is a specification. My invention relates to telegraph-alphabets, and it has for its object to simplify such alphabets, and more especially to provide a complete telegraph-alphabet in which each and every letter or character may be transmitted by the use of a single impulse; and to these ends my invention consists in a telegraphic alphabet having the characteristics hereinafter more particularly set forth. In the accompanying drawings I have illustrated my invention sufficiently to enable those skilled in the art to understand the same, in which Figure 1 is an enlarged detail view illustrating the principles on which my invention is based; and Fig. 2 shows a continuous line, including the entire alphabet and certain punctuation marks, characters, and signs made in accordance with my invention. Heretofore many attempts have been made to improve and simplify the ordinary code of signals comprising the alphabet or characters necessary to be transmitted in telegraphic operations, and without attempting to recite them and state their distinguishing features in detail, it maybe said that they differ from my improved alphabet, as will more clearly appear hereinafter. One of the special features of my alphabet is its adaptation to the transmission of cablemessages, where the impulses which can be transmitted in a given time are limited to a comparatively small number, owing to the static capacity and other qualities of the cable, and in the use of which it has been demonstrated that it is most advantageous to send into the line successive currents of alternating polarity, and, as will appear hereinafter, as each and every one of the letters or characters of the alphabet can be produced by a single electrical impulse or reversal of polarity, the advantages of the use of my alphabet in this connection will be apparent. I will now proceed to describe the characteristics of my alphabet, and it will be un- Serial No. 562,631. (No specimens.) derstood that it may be used in connection with various forms of electrical devices or machinery, but it is intended more particularly for use in connection with a transmitter such as is shown in my application, Serial No. 563,87 5. Referring more particularly to Fig. 1, which shows an enlarged view of a portion of my alphabet, it will be seen that there is what I have termed a zero line a, and while this is indicated in the drawings as a real line, in practice it will preferably be an imaginary line. Each and every letter or character of my alphabet comprises a lateral line b, which extends on each side of the zero line a and crosses the same, and a longitudinal line 0, which extends parallel with the Zero line and is connected to the lateral line b. In all of the letters or characters the lateral line is of the same length, while the longitudinal line varies in length for the different characters. It will thus be seen that all the letters or characters can follow each and any one of the others, making a continuous line or record, well adapting the alphabet for use with the siphon ordinarily used in cable practice. It will further be seen that the longitudinal portion of each letter or character maybe placed on either side of the imaginary or zero line a, while its lateral line crosses the same, extending preferably from the end of the next preceding letter or character. In practice, as the receiving-strip is travelin g constantly, the lateral line naturally assumes a slight inclination to the longitudinal line, and the degree of this inclination depends upon the speed at which the receiving strip travels, but as this strip is supposed to travel at a uniform rate of speed, all the lateral lines will have the same angle with respect to each other and with respect to their longitudinal extensions. From the above it will be seen that with my improved telegraphic alphabet each and every character is composed of a lateral line, which is uniform in length in all the characters, and a longitudinal line, which varies in length in each and every character, and it is immaterial on which side of the imaginary line these longitudinal lines may appear. It will be observed that the record is a continuous record or line, and that each and every letter or character is made by a single impulse or reversal of current. WVhile I have shown the character representing a space as having the shortest longitudinal line, and the longitudinal lines increasing in regular order of the alphabet, it is evident that I-can change the relations of the letters to the length of the longitudinal lines to suit any particular character of work. For instance, the shortest longitudinal line can represent e, and the next t, or any other letter or character,and the next one a, and so on, according to the relative values or uses of the letters. It will further be observed that it is immaterial from which side of the longitudinal line the lateral line extends, that is, whether it extends from the right or the left of the longitudinal line, but in all instances it extends across the imaginary zero line. This is a very important feature, as it provides for a continuous record, regardless of the relative order of the letters or characters used, and any letter or character may follow immediately after any other letter or character and be entirely distinct and definite, and the longitudinal line of each succeeding character will be parallel with and on the opposite side of the zero line from the longitudinal line of the character which immediately precedes it. So also the lateral line of each character extends from the terminal of the longitudinal line of the next preceding character. lVhile I have thus described and illustrated the preferred form or embodiment of my invention, it is evident that the essential features can be variously carried out and the results of my invention fully attain ed. Thus, for instance, while I have shown the alphabet used to make a continuous record, as is naturally done with the ordinary siphon recorder, it is evident that the so-called lateral lines I need not absolutely appear in the record, as these practlcally serve only in determining the length of the longitudinal line, that is, characteristic is the same whether the im pulse which transmits the letter is of positive or negative polarity. In other words, in my alphabet letters are transmitted by successive alternations of polarity, each impulse representing a letter and the letter being determined solely by a characteristic independent of the polarity of the impulse, that is to say, by the length of the impulse. What I claim is 1. A telegraphic alphabet for transmission of impulses successively alternating in polarlty, in which each letter is represented by a single impulse and determined by a characteristic independent of the polarity of the impulse, substantially as described. 2. A telegraphic alphabet for transmission of impulses successively alternating in polarity, in which each letter is represented by a single impulse and determined by the length of the impulse independent of its polarity, substantially as described. 3. The telegraphic alphabet herein described, in which each of the characters comprises a lateral line and a longitudinal line, the lateral line in each and all of the characters being of the same length, and the longitudinal line in each and all of the characters varying in length. 4:- A telegraphic alphabet substantially as herein described, in which each of the characters comprises a lateral line and a longitudinal line, the lateral line extending across an intermediate zero line, and each succeeding longitudinal line being parallel with and on the opposite side of the zero line from the longitudinal line of the character which immediately precedes it. 5. A telegraphic alphabet substantially as herein described, in which each character comprises a lateral line and a longitudinal line, the lateral lines of all the characters being of the same length and the length of the longitudinal line of each character varying from all the others, and the lateral line of each character being connected to the terminal of the longitudinal line of the character next preceding it. 6. A telegraph-alphabet in which the characters are distinguished by the distance between two indicating-points. 7. A telegraph-alphabet in which two distinguishing-points and the length of a line connecting the same designate the character. 8. In a telegraphic alphabet, characters formed by the combination of a lateral and a longitudinal line, each lateral line crossing, and each alternate or succeeding'longitudinal line of each succeeding character, being parallel with and on the opposite side of a zero line from the longitudinal line of the character which immediately preceded it. 9. A telegraph-alphabet in which the characters are formed by placing designatingpoints a distinguishing distance apart each alternate designatingpoint being to the right or left of a zero line. 10. A telegraph-alphabet in which characters may be formed in groups of two the said two characters being of equal length and distinguished each from the other by the position it occupies to the right or left of a zero line. In testimony that I claim the foregoing as my invention I have signed my name, in presence of two witnesses, this 14th day of September, 1895. 7 SAMUEL V. ESSI'CK. \Vitnesses: E. P. ESSIOK, I. A. DUNDAS. IOQ Referenced by
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SeaGull Lighting Three-Light Fluorescent Chandelier Fixture, Serenity Collection, Brushed Nickel. Excavated Alabaster Glass Shades. Uses three GU24 self-ballasted lamps, each 13W maximum - included.
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StartUpHire is the place to find Marketing jobs in and near Milpitas. Review the list below of Marketing Milpitas jobs. These Marketing jobs represent some of the most rewarding careers available. You can refine your job search for Marketing jobs in Milpitas by adding a job title, company name, or keyword to the search box above … or click the "Advanced Search" link for more options. Don't see the employment opportunity you're looking for? Check back soon for more Marketing jobs in Milpitas, or sign up for an email alert (link in upper left) to receive periodic updates on new Marketing jobs in Milpitas, CA.
Build software. Reach 500 million users. Change lives. That?s what we?re doing at Lithium. And you can do it, too. If you want to put your stamp on the digital customer space and enjoy yourself along the way, come join the team. We?re looking for seriously passionate, fun,
1/30/2015 Emeryville, CA Save This JobWe are looking for an entrepreneurial growth expert to bring their passion in driving growth through online marketing and advertising initiatives. Responsibilities: Develop analytics-driven online advertising programs at scale while maximizing ROI. Leverage very large
1/10/2015 Palo Alto, CA Save This Jobat Houzz Palo Alto Houzz is seeking extraordinary people to transform the home remodeling industry. Located in downtown Palo Alto, we are revolutionizing the way people envision, design and build their homes. We are looking for a talented Branding and Marketing Designer who is
1/10/2015 Palo Alto, CA Save This JobWe?re looking for a Partner Product Marketing Lead to help us shape the future of Stride. We're consumer-focused and user growth is central to the success of our growing startup. As Stride?s lead Partner Product Marketing Lead, you will lead partnership growth and
1/6/2015 San Francisco, CA Save This JobDirector or Sr Manager of Product Marketing Los Altos, CA Product Management Elasticsearch is on a mission to make real-time data exploration easy and available to anyone. We spend our days engineering the world?s most advanced open source search and analytics engine, which is
3/2/2015 Los Altos, CA Save This JobLocation:CA-Pleasanton Job Code:746 Description Ellie Mae (NYSE:ELLI) is a leading provider of enterprise on-demand solutions, including an online network, software and services for the residential mortgage industry. Ellie Mae is leading the mortgage industry into the future,
2/18/2015 Pleasanton, CA Save This JobAbout the job: We are looking for a Product Marketing Manager who is passionate and savvy about introducing products in new geographies. As a PMM focused on localization, you will be responsible for taking Twilio?s global product offering and making it look, feel and sound right
2/15/2015 San Francisco, CA Save This JobJob Type: Full-Time Location: San Mateo, CA Department: Marketing RingCentral provides cloud computing based business phone systems designed for today's mobile and distributed business world. The RingCentral technology platform eliminates the need for expensive and technically
2/13/2015 San Mateo, CA Save This JobWe're looking for an event marketing coordinator who is passionate about building great events and evangelizing an amazing product that will be used by millions of customer facing professionals worldwide. Your job will be to take charge and plan/execute a major user conference
2/11/2015 Mountain View, CA Save This JobLocation: Palo Alto or Portland, CA, United StatesApply Product Marketing Associate Summer Intern ABOUT JIVE SOFTWARE Jive Software is the leading provider of modern communication and collaboration solutions for business. Our products empower people and organizations to work
2/6/2015 Palo Alto, CA Save This JobHearsay Social is looking for an experienced marketer with exceptional PR, writing and communication skills. If you are passionate about making an impact and want to be part of a growing team - this role is for you. As a Marketing Communications Manager, you will own public
2/5/2015 San Francisco, CA Save This JobAbout Ticketfly Ticketfly is making life better for the live events community with innovative technology that improves the fan experience from discovery to attendance and beyond. We are challenging the status quo by centering the experience around the fan and building a powerful
2/4/2015 San Francisco, CA Save This JobPosition Summary The VP of Marketing, Loyalty, develops and manages the loyalty program with the goal of increasing customer retention and acquisition. The ideal candidate would have experience developing retail partnerships and strategic alliances that increase membership and
2/2/2015 Foster City, CA Save This JobJob Number16111 Job TitleMarketing Compliance Attorney CitySan Francisco State/Province/CountyCalifornia CountryUnited States Description Marketing Compliance Attorneys Axiom is hiring outstanding Marketing Compliance Attorneys in San Francisco. Axiom is a recognized leader
1/29/2015 San Francisco, CA Save This JobRequisition ID10001BR Job TitleProduct Marketing Manager LocationCalifornia - LitePoint - Sunnyvale HR-CA100 Employment CategoryRegular Full Time Duties & Responsibilities LitePoint is seeking a highly experienced product marketing manager who can lead the creation of strongly
1/20/2015 Sunnyvale, CA Save This JobFulltime, Palo Alto / Copenhagen issuu is the world's leading digital publishing platform. We're looking for a new member to join our fantastic team. With amazing people, unique ideas and stunning technology, we're changing the future of publishing today. Are you the best at
1/16/2015 Palo Alto, CA Save This JobSR./LEAD PRODUCT MARKETING MANAGER, XAMARIN TEST CLOUD Your Role: You?ll be the lead marketer launching a revolutionary new product for the fastest-growing company in mobile software development. Xamarin is launching a revolutionary new service for mobile testing - Test Cloud -
3/3/2015 San Francisco, CA Save This JobWe are looking for someone who is passionate finding insights in complex data sets that can power our business. The ideal candidate has the ability to leverage disparate, complex data sources to unearth insights. These insights will drive marketing decision-making and shape the
3/2/2015 San Francisco, CA Save This JobHead of Marketing: You are a seasoned consumer product marketing leader who can grow communications, community, and public relations at IFTTT. We have a challenging story to tell, with the potential to change the way people use the internet. Experience building and scaling a
2/11/2015 San Francisco, CA Save This JobThe Senior Web Marketing Specialist is responsible for driving the overall website strategy and search engine optimization. This role will drive innovation and growth through the design and development of website functionality that maximizes customer engagement, site experience,
2/10/2015 Menlo Park, CA Save This Job


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Josh Ritter (born October 21, 1976) is an American singer-songwriter, guitarist and author who performs and records with The Royal City Band. Ritter is known for his distinctive Americana style and narrative lyrics. In 2006 he was named one of the "100 Greatest Living...Wikipedia
Age: 38
Born: 21st October, 1976, Moscow, Idaho
Height: Height Unknown
Golden Age of Radio (2002)
Golden Age of Radio is the second studio album by American singer-songwriter Josh Ritter. It was Ritter's first album to be released nationally after he was signed to Signature Sounds. According to his official website, Golden Age of Radio was originally self-released in 2001 and passed out at shows. This self-pressed version contained a different, solo version of the title track called "Country Song," different mastering, and a different track order. [1]


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- Artist: Remarc
- Links: Remarc interview and myspace
Most of us first heard Remarc when darkside anthem Ricky was released back in '93. He went on to produce some of the most rinsingest jungle imaginable by becoming the ultimate don of the Amen break. His releases on Suburban Base, Kemet, Street Tuff, Dollar and White House are all sought after classics and now that drum'n'bass has turned into 2-step, clownstep or whatever, and all you young'uns think that Squarepusher invented the Amen break mash-up, that's why we've re-released them on the Sound Murderer album. Stop press! We got part 2 - the Unreleased Dubs 94-96 - still rinsing, just not classics. Check the mp3s please...
New Releases
Live Dates
- Mar 27, 2015 - Frog Pocket at The Cube (Bristol)
- May 15, 2015 - Chevron at Bloc (Autumn Street) Unit 3; 39 Autumn St; Hackney Wick; London E3 2TT; (London)


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Modern Superhero Nursery
Modern super-hero nursery - love the fun pops of color in the mobile and storage baskets! {see more nursery ideas at projectnursery.com}
Also on these boards
Related Pins
Walk in the Park-themed Nursery - we love the pop of Bahama Blue from the Devon crib from Stacey Craven Cottages! #nursery
Cool #Superhero theme nursery. Click for more DIY pics. #Baby #Nursery #DIY
Modern Eclectic Safari Nursery Safari Nursery Boy Nursery Giraffe Elephant Lion Modern Nursery


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Tea Company Faces Backlash in Starbucks Acquisition
Description:Loose-leaf tea retailer Teavana is facing backlash as it prepares to be acquired by Starbucks Corp. Analysts say Starbucks could do better, and short-sellers are speculating that the deal would fall through. Annie Gasparro reports on Markets Hub. Photo: Reuters. (3:56)
Source: WSJLive
Tags: Teavana Faces Backlash in Starbucks Acquisition , Loose-leaf tea retailer , Starbucks Acquisition , tea company


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Book your room at Lake City Motel
Classic Double Room, 1 Double Bed, Kitchen
Max Occupancy: 2 guests (up to 1 child, 1 infant)Smoking Classic Double Room, 1 Double Bed, Kitchen
Max Occupancy: 2 guests (up to 1 child, 1 infant)Comfort Double Room, 1 Queen Bed
Max Occupancy: 2 guests (up to 1 child, 1 infant)Smoking Comfort Double Room, 1 Queen Bed
Max Occupancy: 2 guests (up to 1 child, 1 infant)Grand Room, 2 Double Beds, Kitchen
Max Occupancy: 4 guests (up to 3 children, 3 infants)Smoking Grand Room, 2 Double Beds, Kitchen
Max Occupancy: 4 guests (up to 3 children, 3 infants)Dartmouth motel with free self parking
Situated in Dartmouth, this motel is close to Mic Mac Mall, Dartmouth Heritage Museum, and Shubie Park. Also nearby are Dartmouth Crossing and Quaker House.
Property Features
Lake City Motel provides complimentary wireless Internet access, laundry facilities, free self parking, and tour/ticket assistance.
Room Amenities
Televisions come with cable channels. Guestrooms also feature complimentary wireless Internet access, refrigerators, and microwaves.
Information missing or incorrect? Tell us!Hotel Amenities
Hotel Amenities
Lake City Motel features tour/ticket assistance and laundry facilities. Public areas are equipped with complimentary high-speed wireless Internet access. Onsite self parking is complimentary.
- Total number of rooms - 31
- Number of floors - 2
- Tours/ticket assistance
- Free WiFi
- Laundry facilities
- Free self parking
- Number of buildings/towers - 1
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Free self parking
Room Amenities
- Air conditioning
- Ceiling fan
- Phone
- Free local calls
- Refrigerator
- Hair dryer (on request)
- Desk
- Iron/ironing board (on request)
- Microwave
- Cable TV service
- Free WiFi
Hotel Policies
Check-in time starts at 2:00 PM
Check-in time ends at midnight
Special check-in instructions:
Check-out time is 11:00 AM
Payment types
Pets allowed, Maximum number of pets per room 1, Pet maximum weight in lb is 10
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
No rollaway/extra beds available
No cribs (infant beds) available
No elevators
- Pet fee: CAD 10 per pet, per night
We should mention
This property allows pets in smoking rooms only (surcharges apply and can be found in the Fees section). Guests can request one of these rooms by contacting the property directly, using the contact information on the booking confirmation.


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Query Result:
Your query was: Q8NDV3
Q8NDV3 SMC1B_HUMAN ; Structural maintenance of chromosomes protein 1B; SMC protein 1B; SMC-1-beta; SMC-1B; Homo sapiens (Human).
Remodel this Protein
New template structures may have become available very recently, which would allow building a more reliable model. Would you like to submit the target protein sequence to our registered modeling services now?


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StartUpHire is the place to find PRODUCER / PROJECT MANAGER jobs. Review the list of PRODUCER / PROJECT MANAGER career opportunities to the left. These PRODUCER / PROJECT MANAGER jobs represent some of the most rewarding careers available.
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Vertafore PLM is always looking for dynamic and passionate people to join our team! We have recently added a new career opportunity for a Project Manager position to our Professional Services team. A Project Manager provides consulting services, project management, software
2/12/2015 East Lansing, MI Save This JobNew Relic Creative Services Project Manager San Francisco, CA At New Relic, we build software tools that developers use to improve the performance of their apps. We're solving hard problems that most people never think about, whilst waking up the sleepy world of performance
3/3/2015 San Francisco, CA Save This JobJustFab Inc. is seeking an energetic Production Manager to join our fast-fashion production team. This role will assist the Executive Producer with the planning, facilitation, and day-to-day operations pertaining to all JustFab Inc. photo, video, and commercial shoots. This
2/12/2015 El Segundo, CA Save This JobAbout Agility Agility Fuel Systems is the leading designer and producer of alternative fuel storage and delivery systems for heavy duty trucks, buses and specialty vehicles. Our systems can be fueled by compressed and liquid natural gas, as well as hydrogen and other
1/4/2015 Charlotte, NC Save This JobHuman Resources Manager Charlotte, North Carolina About Agility Agility Fuel Systems is the leading designer and producer of alternative fuel storage and delivery systems for heavy duty trucks, buses and specialty vehicles. Our systems can be fueled by compressed and liquid
2/3/2015 Charlotte, NC Save This JobID 2015-2921 Job Locations US-NY-New York Category Marketing More information about this job: What We're Looking For: The Marketing Web Producer role will work with various stakeholders across the marketing department, UI/UX team, and tech team to deliver a first-class
2/3/2015 New York, NY Save This JobLocation : Thousand Oaks CA US 91320 % of Travel Required : None Job Type : Full Time Shift/Hours : First Shift (Day) Career Level : Experienced (Non-Manager) Education : Associate Degree Skill : Information Technology -> Database Administrator Media Services -> Audio Visual,
2/5/2015 Thousand Oaks, CA Save This JobJob Description Caring.com, part of the Bankrate family of companies, is the leading online destination for people struggling with the day-to-day realities of caring for aging parents, spouses or other loved ones. We provide much needed information, emotional support and access
1/21/2015 San Mateo, CA Save This JobCafeMom is seeking a Digital Photo and Video Editor to join the team launching an exciting new mobile property for millennial Latinas. This person will be primarily responsible for working with a team of freelancers and senior editors to ideate and generate great multimedia
3/3/2015 New York, NY Save This JobThe German Localization QA Tester provides language localization testing services for all Trion products in its working language. The Localization QA Tester reports directly to Localization Manager and works closely with internal and external linguistic testing team, translators,
1/9/2015 REDWOOD SHORES, CA Save This JobThe Opportunity The Public Relations & Events Intern will support the Communications department. This role reports directly to the PR Manager but will work alongside all areas of the department including PR, Events and Internal Communications. The intern will become fully
1/30/2015 New York, NY Save This JobGilt Groupe is looking for excited, passionate and hard-working undergraduate students for this year?s Summer Internship Program! This summer, we will host interns across the business to gain experience in our fast-paced luxury e-commerce organization for 10 weeks, from June 8,
1/30/2015 New York, NY Save This JobAbout Spongecell: Spongecell is an award-winning advertising technology company that transforms standard ads into dynamic, interactive ad experiences that run anywhere on the web. Spongecell's data-driven ad solutions help brand advertisers and their creative and media agencies
12/30/2014 New York, NY Save This Job


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Price: | $110.00 + $4.99 shipping |
Item Weight | 8.7 pounds |
Product Dimensions | 27.5 x 22.5 x 21 inches |
Item model number | K2564 |
Minimum weight recommendation | 16 Ounces |
Maximum weight recommendation | 25 Pounds |
Number of items | 1 |
Batteries required | Yes |
Best Sellers Rank |
#12,081 in Baby (See top 100)
Shipping Weight | 8.7 pounds (View shipping rates and policies) |
Shipping | Currently, item can be shipped only within the U.S. |
Shipping Advisory: | This item must be shipped separately from other items in your order. Additional shipping charges will not apply. |
This seat is also safe and secure, thanks to the three-point restraint and a pad that fully supports baby's head, neck, and shoulders.
Two Modes for Parent-and-Baby or Independent Play
The Rainforest Bouncer gives you the option of enjoying playtime with baby, or letting him or her play independently. The parent-activated mode features six longer, continuously playing songs, while the baby-activated mode--which kicks off when baby bats at the hanging toys to activate the light-up waterfall and peek-a-boo action--has six shorter songs plus three sound effects that serve as a reward for baby when he or she plays actively with the toys. You can also turn on calming vibrations and alter the volume, so baby can wind down and prepare for quiet time or a nap.
The Rainforest Bouncer measures 19.3 x 17 x 5.1 inches (WxHxD) and weighs 8.4 pounds.


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We want to ensure that making a return is as easy and hassle-free as possible! If for any reason you decide that your purchase just isn't for you, simply return the item within 30 days of receipt and we'll cover the return shipping when you choose our FREE Pre-Paid Return Shipping Label. Learn more about our return policy.
Shop now and get Free Value Shipping on most orders over $29.95 to contiguous 48 states, DC and to all U.S. Military APO/FPO/DPO addresses.
Champion Traps and Targets .22 Single Spinner Target - 40988 on sale and available from our online store. OpticsPlanet, Inc is an Authorized US Distributor for Champion Traps and Targets Targets.
America's favorite rimfire spinning target is now easier to transport and store. The .22/.17 HMR Single Spinner Compact Target features the same challenge of its big brother but comes in an easy-to-assemble design. For use at any distance greater than 25 yards (for .22 LR) and greater than 100 yards (for .17 HMR or .22 WMR), this spinning metal target has detachable legs and a rugged solid steel design.
Champion is offering a single spinner for use with .22 caliber rimfire rifles and pistols at any distance. Champion rimfire targets can be used with magnum loads like .22 WMR or .17 HMR if you put them at 100 yards or farther. Hear the clang and see it spin when you hit your mark.


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This was not see through for me and I'm wearing neon underwear. Very flattering! A little long on the legs but I'm 5'2" so that happens a lot. Highly recommend :)
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This is a cute jumpsuit--on the hanger. But once you wear it, the material is super sheer--everything is exposed from the waist down. Online, the material doesn't look as thin. Also, you must be very gentle w/ the zipper b/c the material is so thin, it can easily get stuck/snag. The must be returned, which is a bummer b/c its a very unique piece.
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Mass. developer to begin work on Odenton project
$60M complex to include shops, apartments
- Daniel J. Sernovitz
- Staff
The long-awaited Odenton Town Center will start to take shape in early July, 15 years after Anne Arundel County officials came up with the concept for the 1,600-acre community of shops, homes and offices.
Dolben Company Inc. plans to start work on the Village at Odenton Station, a $60 million retail and residential development that is part of the town center complex and will be built near the Odenton MARC train station. The Massachusetts-based developer plans to start utility work at the site in the first week of July.
Dolben is hoping to start work on the project as soon as possible to take advantage of one of the largest economic development opportunities to come to Greater Baltimore in decades — BRAC.
The site is less than two miles from Fort George G. Meade, where the Pentagon is moving several government agencies under its Base Realignment and Closure plan. About 5,800 military jobs and at least twice as many defense contractor workers are expected to relocate to Fort Meade. They will need places to live, eat, work and shop.
The military agencies moving to Fort Meade must be in place by September 2011. But a second wave of defense contractors following their government clients to the area are expected to take longer to relocate. What's more, many of those government and private contract workers are expected to commute initially from Arlington, Va., where the largest of the incoming military agencies is now based.
Dolben, which has a regional office in Odenton, is timing its project to meet that second wave, said Matt Bitar, regional project manager for the company. Construction at the Village at Odenton Station — to include 235 apartments and 56,000 square feet of retail space — is expected to be completed by 2012.
The Village is one of several projects that make up the town center, to include 400,000 square feet of residential and commercial space when it is fully developed. But that could take a while.
Anne Arundel County officials are trying to resolve a handful of issues keeping additional construction from taking place. The biggest of those is a lack of water and sewer capacity to handle the additional development. It also needs to install a Town Center Boulevard that will link the projects together.
The Anne Arundel Economic Development Corp. has tried to negotiate deals that would resolve those issues, said Robert L. Hannon, CEO of the economic development group. One of the major challenges has been working out agreements with developers to pay for parts of those upgrades, expected to cost $33 million and take three years to complete.
Hannon said he hopes to seek Anne Arundel County Council approval for those deals by early fall. His office plans to work with developers — among them AJ Properties, Osprey Property Co. and Halle Cos. — on their development projects so they can start building as soon as those public improvements are completed. Dolben has arranged to draw its water from an adjacent property owner, meaning it is not impacted by those issue, Bitar said.
Dolben has retained Metropolitan Management Co. to market the Village's retail space. That has been a tough sell so far because most retailers and restaurateurs are unwilling to commit to a project that isn't built yet, said Patricia Palumbo, director of leasing and marketing for Metropolitan Management.
Palumbo said there has been interest from several tenants, including an Italian restaurant, in large part because of Fort Meade. The 110,000 people who work at the military base are a strong selling point for merchants scouting new locations.
"Once they see something coming out of the ground, I think we'll see the commitments that we need," Palumbo said. "Nobody is even willing to commit to a letter of intent unless they can see something."
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Welcome, Sign In
Three Parent IVF Coming Soon?
Description:A new method of IVF makes it possible to have 3 parents donate genetic material to create a baby, and possibly avoid genetic defects. But that doesn't mean we should. (19:03)
Source: HuffPost Live Segments
Tags: huffpost live , in vitro fertilization , live video , three parent genes


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From Wikipedia, the free encyclopedia - View original article
Michelle Pierce | |
Born | Michelle Pierce Palo Alto, California, USA |
Occupation | Actress |
Years active | 2004–present |
This biographical article needs additional citations for verification, as it includes attribution to IMDb. (November 2011) |
Michelle Pierce | |
Born | Michelle Pierce Palo Alto, California, USA |
Occupation | Actress |
Years active | 2004–present |
Michelle Pierce is an American actress.
Pierce was born in Palo Alto, California. She also had two sisters and one brother. Her great-grandmother was Helen Bray, star of many silent films during the early 20th century.
Pierce attended UCLA and after graduating landed roles on series like CSI: NY and recurring roles on the soap opera Days of Our Lives. She has also appeared in Desperate Housewives, CSI: Miami, and Rules of Engagement, among others. She also had a small role on the 2007 blockbuster Transformers.
On March 2, 2010, Pierce made her debut as a recurring character on CBS's show NCIS, playing the girlfriend (and later fiancée) of series co-star Brian Dietzen's character Jimmy Palmer.
This article about an American film and television actor is a stub. You can help Wikipedia by expanding it. |


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Ben Gordon
Hornets hold off Magic with help from Mo Williams' double-double
points and nine rebounds. Orlando has lost three straight since a season-high three-game win streak. A jumper by Ben Gordon trimmed what had been a 15-point Hornets advantage to 74-70 in the fourth quarter. But the Hornets quickly responded
Questions out of Left Field: Ben Gordon
Questions out of Left Field: Ben Gordon Description Transcript 0 0 0 0 0 Close More Videos + SHOW COMMENTS + Powered by Livefyre
Questions out of Left Field: Ben Gordon
Michael Kosta of 'Crowd Goes Wild' conducts an unusual Q & A with Ben Gordon .
Magic fire coach Jacque Vaughn after 2-plus seasons
extensive roster makeover since their arrivals. The moves brought in eight new players, including veterans Frye and Ben Gordon , to fortify a roster that already featured a young core of Victor Oladipo and Nik Vucevic. But the team struggled out
Hornets-Magic Postgame Locker Room Interviews | Magic Basketball Online - Orlando Magic Insight - Your Favorite Blog's Favorite Blog
Elfrid Payton , Nikola Vucevic , Victor Oladipo , and Ben Gordon . Elfrid Payton: Nikola Vucevic: Victor Oladipo: Ben Gordon : Adam Papageorgiou is Owner/Editor of MBO and Founder
Magic shoot 59 percent en route to victory over Bulls
Orlando received a considerable boost from its bench, which scored 25 points in that span. TIP-INS Magic: Ex-Bulls G Ben Gordon returned to Chicago, where he spent the first five seasons of his career. ''Played in some big games, hit some big
Charlotte Hornets at Orlando Magic game preview
Maybe if we had a couple of more minutes, the game would have (gone) differently," said former Charlotte guard Ben Gordon , who had 14 points. "We can't dig a hole for ourselves like that." The Magic needed a 41-point fourth quarter
Rookies Elfrid Payton, Devyn Marble add scrappiness as Magic nearly pull off comeback
guarding Joe Johnson in the fourth quarter of a furious comeback attempt. But the two rookies, along with veterans Ben Gordon and Channing Frye plus third-year pro Evan Fournier, wound up making matters interesting Friday night for the fans
Magic can't hold off Cavs
twelve Frito attempts tonight so I hope we try to continue to be aggressive. John what was your rationale for playing Ben Gordon for not majority of the fourth quarter and include your offensive benefited from having Alfred. Orchestrate the office
to continue to be aggressive. John what was your rationale for playing Ben Gordon for not majority of the fourth quarter and include your offensive benefited from having Alfred. Orchestrate the office space and the coach -
Fourth-quarter woes getting tiresome for Magic
in which the Magic led by nine points late in the third quarter and trailed only 84-83 after a pullup 3-pointer by Ben Gordon with 6:04 remaining got away from them in all-too-familiar fashion. "Look at a lot of the games we have lost


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Door switch broken on my frigidair microwave Jennifer W. • Flatwoods, KY • June 16, 2014 My Repair & Advice Replaced switch Was this review helpful to you?
My original probe lasted only a few times Elizabeth R. • Gay, WV • December 26, 2014 My Repair & Advice Ordered a replacement for defective part. Very happy with the shipping. Very quick. And the price was very fair. Was this review helpful to you?


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Open season begins for purchase of desktop, laptop PCs
The Army will open its semiannual consolidated buying program for desktop and laptop PCs on Jan. 11, officials said today.
During the consolidated buying period, which will run thtough March 31, Army Desktop and Mobile Computing-2 vendors furnish consolidated buying discounts on top of pre-negotiated low prices for commercial, off-the-shelf products, Army officials said.
The consolidated buying program offers four desktop and four laptop configurations, with available options and upgrades, from various manufacturers and resellers such as CDW-G, Dell, Emtec, Hewlett-Packard, ITG, NCS Technologies, Telos and Transource. All desktops and laptops are preloaded with the latest standard baseline configurations embodied in the Army Golden Master (AMG) program, the officials said.
This year the program has a new category for a Workstation and a 64-bit operating system that conforms to the AMG guidelines, the officials said.
The consolidated buying program is managed by the Computer Hardware, Enterprise Software and Solutions (CHESS) office, which reports to the Army Program Executive Office, Enterprise Information Systems.
The Army's Information Technology, E-Commerce and Commercial Contracting Center solicits the requirement. Contracting officers can go to the CHESS Web site and view a side-by-side comparison of specifications and prices, evaluate them in accordance with their procedures, and place an order, officials said.
Army customers should coordinate their desktop and notebook acquisitions through their local information management directorate or equivalent for National Guard and Reserve in accordance with Army Regulation 25-1, officials said.
Last month the Army awarded a contract to help it consolidate purchasing of combat training systems.
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President Obama's proposal to boost government coordination with the private sector got a warm welcome in the House Homeland Security Committee.
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FCW investigated efforts by the departments of Defense and Veterans Affairs to improve a joint data repository on military and veteran suicides. Something as impersonal and mundane as incomplete datasets could be exacerbating a national tragedy.
Despite delays, the program is at a critical point for determining the ultimate impact of cloud technology in the government space.
In an interview with FCW, the Department of Veterans Affairs' chief technology officer talks about overhauling the digital experience for VA customers.
The National Information Exchange Model's usefulness extends far beyond its origins in justice and law enforcement.


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Capgemini Senior Manager Interview Questions in United States
Interview Experience
Interview Experience
Getting an Interview
Getting an Interview
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Interviews for Top Jobs at Capgemini
- Consultant (105)
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Senior Manager Interview
I applied through an employee referral. The process took a week – interviewed at Capgemini.
Easy if you are referred by employee
- Will try to get your salary pushed down in negotiations Answer Question
Other Interview Reviews for Capgemini
Senior Manager Interview
Application DetailsI applied online. The process took 3 weeks – interviewed at Capgemini.
Interview DetailsUnfortunately, the interview process was ardrous and unclear? I applied for one postion and was contatcted by a second recruiter who NEVER stated and or confirmed that position he was contacting me for?? After discussing career experience, at great length, he presented my credentials to the hiring manager who requested that we meet. However, as I am currently employed and travel,eighty five percent of the time, I asked if we could meet the following week.
The next step was that I recieved an email message stating that I was no loger being considered for the position.
Against, the recommendations of colleagues who have gone through this process, I pursued it anyway.
In short, if you are a senior sales/business development professional, please do not waste your time with this organization.Interview Questions- There were none from my perspective Answer Question
No OfferNegative ExperienceAverage Interview -
Senior Manager Interview
Application DetailsI applied online. The process took 1+ week – interviewed at Capgemini in May 2013.
Interview DetailsPhone screening interview with recruiter...the basics. Phone interview with hiring manager (Partner, Practice Lead). Phone interview with Sr. Partner (overall Practice Leader). Very professional and to the point. However, the final interview felt like an interview for a completely different job. No further communication following final discussion.
Interview Questions- Final interview had extensive technical questions not related to the specific job role. Answer Question
No OfferNeutral ExperienceAverage Interview -
1 person found this helpful
Senior Manager Interview
Application DetailsI applied through a recruiter. The process took 2 weeks – interviewed at Capgemini in March 2013.
Interview DetailsStrictly phone interviews. Initially spoke with a recruiter, then a HR resource, then a couple of my peers with similar level as me, then the engagement manager, then the group VP. After negotiating my salary, I was hired. Spent one week on boarding with a group of other new employees.
Interview Questions- Explain the technology stack at my last employer Answer Question
Negotiation DetailsYes, I negotiated and they agreed.Accepted OfferPositive ExperienceAverage Interview -
Senior Manager Interview
Application DetailsI applied online. The process took a week – interviewed at Capgemini in January 2013.
Interview DetailsExtraordinarily friendly, engaging, and intelligent recruiter who provided a detailed description of the position. The next discussion was with the practice leader who was very experienced in industry. We agreed that another opportunity would be best. Nonetheless, it was a worthwhile interview experience.
Interview Questions- How did our interview process compare with other companies? View Answers (2)
No OfferPositive ExperienceAverage Interview -
Senior Manager Interview
Application DetailsI applied through an employee referral. The process took 5 weeks – interviewed at Capgemini in January 2011.
Interview Detailsapplied through employee referral, had 3 phone interviews, and one in-person interview, in addition to 2 Human Resources interviews, visited local office in Atlanta, elapse time was about a month, interviews were case study types, not too tough, pretty supportive environment, last interview at corporate vice president level
Interview Questions- What will you do in the first year of your work with us? Answer Question
Negotiation DetailsPretty reasonable processAccepted OfferPositive ExperienceAverage Interview -
Senior Manager Interview
Application DetailsI applied through an employee referral. The process took 4+ weeks – interviewed at Capgemini in January 2009.
Interview DetailsVery loose process that seemed more a gut process than a behavioral/detail review.
Interview Questions- Did not really have anything that was challenging. Probably more concerned as to expectations of the employee Answer Question
Reasons for DecliningSuccess criteria was not clear.
Declined OfferNeutral ExperienceEasy Interview
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Valentino Resort 2012 Collection
Valentino Resort 2012
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Valentino Resort 2012
>> An elegant kind of effortless permeated the 42 looks designers Pier Paolo Piccioli and Maria Grazia Chiuri turned out for Valentino's 2012 Resort collection. "If you're not comfortable, you don't look chic," Piccioli stated. To his point, shirtdresses, suits, shifts and jumpsuits were cut in flattering lines around the body, resulting in loosely cinched waists, a-line skirts, and drapey, fluttery sleeves. Ivory lace and soft floral chiffon played easily amongst the feminine — and sometimes flirty— silhouettes, while silk, cotton, and leather in olive, navy, and ochre provided a playful sleekness. "This is about joyfulness and prettiness," Chiuri explained.
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Loved it!
This was a family trip. My wife and I both brought our mothers and we participated in the Maui Marathon. The unit is well located for most anything you want to do on Maui. The room itself is well appointed and was as advertised. The first day, the air conditioner didn't work, I called the owner and she had a new air conditioner installed within hours. You don't get much better service that that!
The view is quite nice. The property is beautifully landscaped. I've stayed on this property many times but this was my first time in a ground floor unit and we loved it. It was a short walk to the BBQ grills and the seawall for sunsoaking and sunset watching. Should you choose to book this unit, you won't be disappointed.


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288 comments found
I'm having the same issues as teddyhedenquist – the theme options and page builder pages in wp admin aren't working… can you please fix?
Please download the latest theme update.
Best regards!
Hi, it would be great if you could get back to me regarding the slider. At the moment my clients page is down due to this. And I still have not received a login details to your support frum. Please get back to me asap. Regards.
We have responded your questions in other comments here.
Best regards!
Hi … first of all: very nice theme!
I have a problem with the navigation. If the navigation is "center" then it is "jumping" to the left for a very short moment when you click on any menu item. Like "shortcodes" in your live preview.
How can I fix that?
Best regards!
Hi moutheme,
any answear to my question after two weeks?
Sorry for the late response. Please can you show us your site url?
Write at our support forum support.moutheme.com.
Best regards!
I wrote at your support forum. Thanks
We have responded you at the support forum.
Best regard!
First off this theme is AWESOME! I feel so stupid but I'm trying to find the LayerSlider and it's no where in my panels and I just want to upload a slider onto my home page. I can't find it as a plugin either. Nor any of the sliders. Please help?
Thank You! You must install the slider plugin, it's included in them package, then create slider and assign it to the page.
Best regards!
I am working on this theme for one of my client …but in backend the easy theme options and page builder option not working correctly mean it is not left sidebar from where we choose the options to change like header,font,general etc..can you help me to resolve this issue
Please download the latest theme version, this issue caused by WP 4. 0 is fixed.
Best regards!
I purchased this theme the other day but there is no "Services" pages in the the psd folder, do you have these available? Can you send them over please?
Sorry, only the psd files included in theme are available.
Best regards!


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Nonferrous markets have begun 2013 in a moderately upbeat mood. Several scrap metal recyclers say that material is flowing at a decent pace.
Nonferrous markets have begun 2013 in a moderately upbeat mood. Several scrap metal recyclers say that material is flowing at a decent pace. "We are having no problem shipping to end sources," one scrap metal dealer says. This is the case for most grades of nonferrous metal. Another scrap dealer describes markets for nonferrous metals as "steady and stable." Recyclers who handle aluminum have cause for optimism in the form of Alcoa's 2012 fourth quarter report, released Jan. 8, 2013. The company says it expects to see a moderately stronger aluminum market in 2013. However, aluminum markets currently are challenging. Prices continue to be volatile, though several scrap metal recyclers point to healthy orders from consumers. One consumer of aluminum scrap says he is receiving positive feedback from his customers through the first quarter of 2013. However, he says concerns linger among manufacturers about the overall health of the U.S. economy and the effects of a possible downturn. A scrap dealer based in the Midwest also reports that industrial scrap generators are running solid production schedules, ensuring the steady flow of material. The challenge has been the supply of obsolete scrap, he says. Throughout the past several quarters, scrap dealers have said they have had to work much harder to get material they need to meet their orders. Obsolete scrap generation typically declines during the first few months of the year, particularly in regions that experience frigid temperatures and snow. While several sources say generation is slightly higher this year than it was at the same time in 2012, scrap recyclers still are scrambling to meet orders. Several sources have been speculating recently that most obsolete material already has entered the recycling stream and that less material is available. With the U.S. economy still sluggish, scrap dealers say they are concerned the overall supply of obsolete material will continue to be lower. Consumers also are replacing their automobiles and white goods less frequently. As does aluminum, copper remains volatile. After a fairly healthy upswing in late 2012 and early 2013, copper prices have softened. In the middle of January, prices fell to two-week lows, influenced by macroeconomic factors, including a strengthening U.S. dollar. A report in the Wall Street Journal notes that Federal Reserve Chairman Ben Bernanke has been a supporter of an "easy money" policy, which works to weaken the U.S. dollar, while strengthening base metals such as copper. The copper scrap market also is being influenced by concerns about the health of the Chinese economy. China, the largest consumer of copper scrap, has seen its economy slow, though it is still growing far faster than the economies of most every other country. While the Chinese economy may continue to soften in the short term, analysts say they expect that a large fiscal stimulus package being introduced by the Chinese government could help strengthen the country's economy, which could result in better prices for copper. In the meantime, several suppliers say copper scrap shipments to China have eased back in advance of Chinese New Year in early February. The stainless steel scrap market continues to show signs of duress. One broker says markets remain weak, with few signs of improvement in the near term. European producers are still saddled with overcapacity and are not active in the market to any degree, sources say.
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When it comes to easy lighting options, all signs point to floor lamps. Not only is it the best way to spice up any of your spookiest corners, our floor lamps are easy to move around so you can maximize light and minimize clutter. Whether you're looking for something colorful and durable for the kids or modern and artistic, our floor lamps collection has exactly what your carpet or hardwood floor is looking for.
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