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Publications (113)690.24 Total impact
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ABSTRACT: Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case--control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG + GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG + GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism.BMC Pulmonary Medicine 11/2013; 13(1):64. · 2.76 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = -0.068 g/L per minor allele (P = 1.20*10(-12)). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population.PLoS Genetics 08/2013; 9(8):e1003585. · 8.52 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD) via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and cystatin C (CST3). We hypothesized that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with COPD phenotypes.Quantitative PCR and enzyme-linked immunosorbent assays/gelatin zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed.The results showed that basal expression level of MMP12 mRNA was inversely related to DL,CO/VA and to FEV1/FVC after correction for multiple comparisons. The expression level of MMP12 protein stimulated with LPS was also inversely related to DL,CO/VA and was positively related to the extent of emphysema. The basal expression of MMP1 mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with FEV1% predicted.We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.European Respiratory Journal 07/2013; · 6.36 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Respiratory diseases are the most frequent chronic illnesses in babies and children. Although a vigorous innate immune system is critical for maintaining lung health, a balanced response is essential to minimize damaging inflammation. We investigated the functional and clinical impact of human genetic variants in the promoter of NFKBIA, which encodes IκBα, the major negative regulator of NF-κB. In this study, we quantified the functional impact of NFKBIA promoter polymorphisms (rs3138053, rs2233406, and rs2233409) on promoter-driven protein expression, allele-specific and total NFKBIA mRNA expression, IκBα protein expression, and TLR responsiveness; mapped innate immune regulatory networks active during respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia; and genotyped and analyzed independent cohorts of children with respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Genetic variants in the promoter of NFKBIA influenced NFKBIA gene expression, IκBα protein expression, and TLR-mediated inflammatory responses. Using a systems biology approach, we demonstrated that NFKBIA/IκBα is a central hub in transcriptional responses of prevalent childhood lung diseases, including respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Finally, by examining independent pediatric lung disease cohorts, we established that this immunologically relevant genetic variation in the promoter of NFKBIA is associated with differential susceptibility to severe bronchiolitis following infection with respiratory syncytial virus, airway hyperresponsiveness, and severe bronchopulmonary dysplasia. These data highlight the importance of negative innate immune regulators, such as NFKBIA, in pediatric lung disease and begin to unravel common aspects in the genetic predisposition to bronchopulmonary dysplasia, bronchiolitis, and childhood asthma.The Journal of Immunology 03/2013; · 5.52 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Peanut allergy (PA) is a common and serious food allergy and its prevalence has increased in the past decade. Although there is strong evidence of inheritance, the genetic causes of this disease are not well understood. Previously, a large-scale genome-wide association study described an association between human leukocyte antigen (HLA)-DQB1 and asthma; the aim of this study was to evaluate the association between HLA-DQB1 and PA. Genotypic and allelic profiles were established for 311 Caucasian members of a well-described Canadian group of children with PA and 226 Caucasian controls. Firth's logistic regression analyses showed associations between HLA-DQB1 alleles and PA for DQB1*02 (P=1.1 × 10(-8), odds ratio (OR)=0.09 (CI=0.03-0.23)) and DQB1*06:03P alleles (P=2.1 × 10(-2), OR=2.82 (CI=1.48-5.45)). This study of HLA in PA demonstrates specific association between two allelic groups of the HLA-DQB1 gene (DQB1*02 and DQB1*06:03P) and PA, highlighting its possible role in the development of this disease.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.13.European journal of human genetics: EJHG 02/2013; · 3.56 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Human beings come in all shapes and sizes. Heterogeneity makes life interesting, but leads to inter-individual variation in disease susceptibility and response to therapy. One major health challenge is to develop "personalised medicine"; therapeutic interventions tailored to an individual to ensure optimal treatment of disease. Asthma is a heterogeneous disease with several different phenotypes triggered by multiple gene-environment interactions. Inhaled corticosteroids and β2-agonists have been the mainstay asthma therapies for 30 years, but they are not effective in all patients, while high costs and side-effects also drive the need for better targeted treatment of asthma. Pharmacogenetics is the study of variations in the genetic code for proteins in signaling pathways targeted by pharmacological therapies. Biomarkers are biological markers obtained from patients that can aid in asthma diagnosis, prediction of treatment response, and monitoring of disease control. This review presents a broad discussion of the use of genetic profiling and biomarkers to better diagnose, monitor, and tailor the treatment of asthmatics. We also discuss possible future developments in personalised medicine, including the construction of artificially engineered airway tissues containing a patient's own cells for use as personalised drug-testing tools.Current Allergy and Asthma Reports 12/2012; · 2.75 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Genome-wide association studies (GWAS) have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL) in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55×10(-151)). The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases.PLoS Genetics 11/2012; 8(11):e1003029. · 8.52 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: BACKGROUND: The innate immune system is essential for host survival because of its ability to recognize invading pathogens and mount defensive responses. OBJECTIVES: We sought to identify genetic associations of innate immunity genes with atopy and asthma and interactions with early viral infections (first 12 months of life) in a high-risk birth cohort. METHODS: Three Canadian family-based studies and 1 Australian population-based case-control study (n = 5565) were used to investigate associations of 321 single nucleotide polymorphisms (SNPs) in 26 innate immunity genes with atopy, asthma, atopic asthma, and airway hyperresponsiveness. Interactions between innate immunity genes and early viral exposure to 3 common viruses (parainfluenza, respiratory syncytial virus, and picornavirus) were examined in the Canadian Asthma Primary Prevention Study by using both an affected-only family-based transmission disequilibrium test and case-control methods. RESULTS: In a joint analysis of all 4 cohorts, IL-1 receptor 2 (IL1R2) and Toll-like receptor 1 (TLR1) SNPs were associated with atopy after correction for multiple comparisons. In addition, an NFKBIA SNP was associated with atopic asthma. Six SNPs (rs1519309 [TLR3], rs740044 [ILIR2], rs4543123 [TLR1], rs5741812 [LBP], rs917998 [IL18RAP], and rs3136641 [NFKBIB]) were significant (P < .05, confirmed with 30,000 permutations) in both the combined analysis of main genetic effects and SNP-virus interaction analyses in both case-control and family-based methods. The TLR1 variant (rs4543123) was associated with both multiple viruses (respiratory syncytial virus and parainfluenza virus) and multiple phenotypes. CONCLUSION: We have identified novel susceptibility genes for asthma and related traits and interactions between these genes and early-life viral infections.The Journal of allergy and clinical immunology 10/2012; · 9.17 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Prior studies have demonstrated that the distal 1.5 kb of the MMP-1 promoter is fundamental in directing the induction of the MMP-1 gene by cigarette smoke. METHODS: To characterize the genetic variants in the MMP-1 cigarette smoke-responsive element, deep re-sequencing of this element was performed on DNA samples from participants in the Lung Health Study. Furthermore, evidence of Sp1 binding to the MMP-1 promoter was assessed using chromatin immunoprecipitation assays and the influence of cigarette smoke exposure on this interaction was evaluated in cultured human small airway epithelial cells. RESULTS: Ten polymorphisms (four novel) were detected in the cigarette smoke-responsive element. Chromatin immunoprecipitation assays to assess the protein-DNA interactions at Sp1 sites in the MMP-1 promoter showed increased binding to the Sp1 sites in the cigarette smoke-responsive element in small airway epithelial cells treated with cigarette smoke extract. In contrast, a Sp1 site outside of the element exhibited the opposite effect. None of the polymorphisms were more prevalent in the fast decliners versus the slow decliners (fast decliners = mean -4.14% decline in FEV1 % predicted per year vs. slow decliners = mean +1.07%/year). CONCLUSIONS: Sequencing analyses identified four novel polymorphisms within the cigarette smoke-responsive element of the MMP-1 promoter. This study identifies functional activity within the cigarette smoke-responsive element that is influenced by cigarette smoke exposure and examines this region of the promoter within a small patient population.Respiratory research 09/2012; 13(1):79. · 3.64 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Accelerated lung function decline is a key COPD phenotype; however, its genetic control remains largely unknown. We performed a genome-wide association study using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation equations were used to assess genetic contributions to lung function decline over a 5-year period in 4,048 European American Lung Health Study participants with largely mild COPD. Genotype imputation was performed using reference HapMap II data. To validate regions meeting genome-wide significance, replication of top SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1) within the regions of interest were selected for tissue expression studies using immunohistochemistry. Two intergenic SNPs (rs10761570, rs7911302) on chromosome 10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after Bonferroni. Further support for the chromosome 10 region was obtained by imputation, the most significantly associated imputed SNPs (rs10761571, rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results were not replicated in four general population cohorts or a smaller cohort of subjects with moderate to severe COPD; however, we show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels of expression were associated with lung function and COPD status. We identified two novel regions associated with lung function decline in mild COPD. Genes within these regions were expressed in relevant lung cells and their expression related to airflow limitation suggesting they may represent novel candidate genes for COPD susceptibility.Human Genetics 09/2012; · 4.63 Impact Factor -
Article: NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.
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ABSTRACT: An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.Physiological Genomics 06/2012; 44(15):754-63. · 2.81 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Cigarette smoking is the leading risk factor for lung cancer. To identify genes deregulated by smoking and to distinguish gene expression changes that are reversible and persistent following smoking cessation, we carried out genome-wide gene expression profiling on nontumor lung tissue from 853 patients with lung cancer. Gene expression levels were compared between never and current smokers, and time-dependent changes in gene expression were studied in former smokers. A total of 3,223 transcripts were differentially expressed between smoking groups in the discovery set (n = 344, P < 1.29 × 10(-6)). A substantial number of smoking-induced genes also were validated in two replication sets (n = 285 and 224), and a gene expression signature of 599 transcripts consistently segregated never from current smokers across all three sets. The expression of the majority of these genes reverted to never-smoker levels following smoking cessation, although the time course of normalization differed widely among transcripts. Moreover, some genes showed very slow or no reversibility in expression, including SERPIND1, which was found to be the most consistent gene permanently altered by smoking in the three sets. Our findings therefore indicate that smoking deregulates many genes, many of which reverse to normal following smoking cessation. However, a subset of genes remains altered even decades following smoking cessation and may account, at least in part, for the residual risk of lung cancer among former smokers. Cancer Res; 72(15); 3753-63. ©2012 AACR.Cancer Research 06/2012; 72(15):3753-63. · 8.65 Impact Factor - Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2012; 19(1):44-5. · 1.29 Impact Factor
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ABSTRACT: Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV(1) and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy "mid-life" volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy "mid-life" volunteers (p<.001). Compared to individuals in the 4(th) quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD.PLoS ONE 01/2012; 7(4):e35567. · 3.73 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: No optimal housekeeping genes (HKGs) have been identified for CD4(+) T cells from non-depressive asthmatic and depressive asthmatic adults for normalizing quantitative real-time PCR (qPCR) assays. The aim of present study was to select appropriate HKGs for gene expression analysis in purified CD4(+) T cells from these asthmatics. Three groups of subjects (Non-depressive asthmatic, NDA, n = 10, Depressive asthmatic, DA, n = 11, and Healthy control, HC, n = 10 respectively) were studied. qPCR for 9 potential HKGs, namely RNA, 28S ribosomal 1 (RN28S1), ribosomal protein, large, P0 (RPLP0), actin, beta (ACTB), cyclophilin A (PPIA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase 1 (PGK1), beta-2-microglobulin (B2M), glucuronidase, beta (GUSB) and ribosomal protein L13a (RPL13A), was performed. Then the data were analyzed with three different applications namely BestKeeper, geNorm, and NormFinder. The analysis of gene expression data identified B2M and RPLP0 as the most stable reference genes and showed that the level of PPIA was significantly different among subjects of three groups when the two best HKGs identified were applied. Post-hoc analysis by Student-Newman-Keuls correction shows that depressive asthmatics and non-depressive asthmatics exhibited lower expression level of PPIA than healthy controls (p<0.05). B2M and RPLP0 were identified as the most optimal HKGs in gene expression studies involving human blood CD4(+) T cells derived from normal, depressive asthmatics and non-depressive asthmatics. The suitability of using the PPIA gene as the HKG for such studies was questioned due to its low expression in asthmatics.PLoS ONE 01/2012; 7(10):e48367. · 3.73 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.Human Genetics 12/2011; 131(7):1105-14. · 4.63 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Oxidative stress induced by smoking is considered to be important in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Heme oxygenase-1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative stress and may play a protective role as an antioxidant in the lung. We determined whether HMOX1 polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects. We genotyped five single nucleotide polymorphisms (SNPs) in the HMOX1 gene in Caucasians who had the fastest (n = 278) and the slowest (n = 304) decline of FEV1 % predicted, selected from smokers in the NHLBI Lung Health Study. These SNPs were also studied in Caucasians with the lowest (n = 535) or the highest (n = 533) baseline lung function. Reporter genes were constructed containing three HMOX1 promoter polymorphisms and the effect of these polymorphisms on H2O2 and hemin-stimulated gene expression was determined. The effect of the HMOX1 rs2071749 SNP on gene expression in alveolar macrophages was investigated. We found a nominal association (p = 0.015) between one intronic HMOX1 SNP (rs2071749) and lung function decline but this did not survive correction for multiple comparisons. This SNP was in perfect linkage disequilibrium with rs3761439, located in the promoter of HMOX1. We tested rs3761439 and two other putatively functional polymorphisms (rs2071746 and the (GT)n polymorphism) in reporter gene assays but no significant effects on gene expression were found. There was also no effect of rs2071749 on HMOX1 gene expression in alveolar macrophages. We found no association of the five HMOX1 tag SNPs with lung function decline and no evidence that the three promoter polymorphisms affected the regulation of the HMOX1 gene.BMC Medical Genetics 09/2011; 12:117. · 2.54 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.Nature Genetics 06/2011; 43(6):539-46. · 35.21 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Genetic studies of lung disease in cystic fibrosis (CF) are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2,061 patients representing the Canadian CF population, 1,137 extreme phenotype patients in the UNC/Case Western study, and 1,323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality-adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power, and avoiding possible distortions. This approach will facilitate large-scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF.Pediatric Pulmonology 04/2011; 46(9):857-69. · 2.38 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Recent research suggests that chronic obstructive pulmonary disease (COPD) may be a disease of accelerated aging. The senescence hypothesis of COPD pathogenesis is supported by in-vitro, in-vivo and clinical studies. The purpose of this review is to provide a comprehensive overview of the senescence hypothesis of COPD and summarize methods that are used to assess cellular aging. Accelerated aging due to exposure to cigarette smoke is hypothesized to induce rapid progression of COPD. Recent studies have shown that COPD patients have enhanced expression of senescence-associated proteins in the lung and in the peripheral circulation compared to healthy controls. Murine models of accelerated aging demonstrate spontaneous emphysematous changes in the lungs, while lungs of COPD patients demonstrate enhanced markers of senescence in fibroblasts and alveolar cells. More recently, studies of telomeres, which shorten with cellular aging, have shown that COPD patients may experience accelerated telomere attrition compared with healthy controls. However, studies to date have been relatively small and have produced heterogeneous results. The evidence for the role of accelerated aging in COPD progression is growing and senescence is one possible molecular pathway by which COPD occurs.Current opinion in pulmonary medicine 03/2011; 17(2):90-7. · 3.12 Impact Factor
Publication Stats
2k | Citations | |
690.24 | Total Impact Points | |
Top Journals
University of Québec in Chicoutimi
- Department of Sciences Fondamentales
Saguenay, Quebec, Canada
St. Paul's Hospital
Saskatoon, Saskatchewan, Canada
University of British Columbia - Vancouver
- • Department of Medicine
- • Department of Pediatrics
- • Division of Respiratory Medicine
Vancouver, British Columbia, Canada
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec, Canada
Laval University
Québec, Quebec, Canada
Universität Basel
Bâle, Basel-City, Switzerland
Vancouver General Hospital
Vancouver, British Columbia, Canada


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Has metal ID tag holders (labels not included) and safety straps for anchoring to the wall. Bronzetone hardware. Composite wood; white painted finish. Assembly required. 16" w x 72 1/4" h x 12" d.
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Make the most of your space with tall cabinets offering plenty of room to hide away canned goods and a host of other items. Four compartments behind eight doors. Composite wood with wood frame. Assembly required. 23 1/4" w x 72" h x 12" d.
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Center fixed shelf and 4 coat hooks (2 on top, 2 on the bottom). Comes with metal ID tag holder (labels not included) and safety straps for anchoring to the wall. Bronzetone hardware. Composite wood; white painted finish. Assembly required. 16" w x 72 1/4" h x 11 3/4" d.
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Design features include crown molding, routed edges, cane door inserts on the Bailey Space Saver and Cabinet (each sold separately). Bailey Cabinet: Cabinet has upper and lower compartments; upper door has a cane insert, the lower one has an adjustable shelf. Composite wood; white painted finish. Assembly…
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…7 3/4" sq. x 25 1/2" h. Space Saver: One adjustable shelf behind cabinet doors. Composite wood; white painted finish. Assembly required. 24" w x 62 3/4" h x 8" d. Floor Cabinet: One fixed shelf and open space behind the cabinet door. Composite wood; white painted finish. Assembly required. 15 3/4" w…
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Beautify your room with meticulous hand-carved elegance. This solid wood cabinet's graceful design and spacious storage make it a wonderful addition to the dining room, living room or hall. Easy to assemble. Rich brown stained finish. 43" w x 35 1/2" h x 16" d.
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Chic metal cabinet with chicken wire front and sides has 2 fixed shelves and a hinged door. Antique black painted finish. 13 1/2" w x 34 1/2" h x 5 1/2" d. Available only in Antique Black.
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…put all of their rich colors on display. 16" w x 24" h x 10" d. Space Saver: Exterior shelf and cabinet with on fixed shelf. 25" w x 64 1/4" h x 9" d. Bathroom Tissue Holder: Wooden dowel holder and stores 3 extra rolls at hand behind its door. 7" w x 24" h x 6" d. Who says you can't live like nobility…
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Prettier than a pile of shoes on your closet floor—and so much less frustrating! This attractive cabinet has six shelves inside to keep your shoes neat and findable, and a mirror on the door ensures that you look your best. Mirror panel is 15" w x 59" h. Holds up to 12 pairs of shoes. Composite wood…
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…decorative door panels on this impressive TV stand lend a sense of grandeur to your media room. Its length is ideal for a wide, flat-screen TV, and its two cabinets provide plenty of storage and display space. Composite wood with wood veneer. Assembly required. Has one single and one double cabinet; 1 adjustable…
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Ronald McNair grew up in Lake City, SC. He grew up to become an astronaut. Tragically, he was on the Challenger mission, which exploded seconds after takeoff...
He Walked Into A Segregated Library. He Wanted To Be An Astronaut. Mission Accomplished.
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He Lost The Vote But Won History With A Few Simple Words That Helped Others Pave The Way To Change
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Use E/M coding audits to train your physicians
Learn how to improve coding in your practice in Part II of this two-part series
As discussed in the April MCCRA, a coding audit is an excellent tool for physician practices to determine what, if any, problems exist in their claims submissions, particularly for E/M codes. Part II of this coding spotlight illustrates how to use the findings of your audits to help your physicians improve their coding practices.
E/M codes affect not just outpatient or office consultations but home, skilled and unskilled nursing facilities, and ED visits, says Jennifer Swindle, RHIT, CCS-P, CPC-EM-FP, CCP, senior coding consultant at PivotHealth in Lafayette, IN. "Many practices audit their office visits. It's harder to get to the hospital records, but those visits also need to meet the documentation guidelines."
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Publications (112)550.91 Total impact
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ABSTRACT: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). Seventy participants were randomized to standard (n = 37, 52.9%) or intensive (n = 33, 47.1%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88.0%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (25.7%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.BMC Infectious Diseases 02/2014; 14(1):89. · 3.03 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Mother to child transmission (MTCT) of HIV-1 remains an important problem in sub-Saharan Africa where most new pediatric HIV-1 infections occur. Early infant diagnosis of HIV-1 using dried blood spot (DBS) PCR among exposed infants provides an opportunity to assess current MTCT rates. We conducted a retrospective data analysis on mother-infant pairs from all PMTCT programs in three regions of northern Tanzania to determine MTCT rates from 2008-2010. Records of 3,016 mother-infant pairs were assessed to determine early transmission among HIV-exposed infants in the first 75 days of life. Of 2,266 evaluable infants in our cohort, 143 had a positive DBS PCR result at ≤75 days of life, for an overall transmission rate of 6.3%. Transmission decreased substantially over the period of study as more effective regimens became available. Transmission rates were tightly correlated to maternal regimen: 14.9% (9.5, 20.3) of infants became infected when women received no therapy; 8.8% (6.9, 10.7) and 3.6% (2.4, 4.8) became infected when women received single-dose nevirapine (sdNVP) or combination prophylaxis, respectively; the lowest MTCT rates occurred when women were on HAART, with 2.1% transmission (0.3, 3.9). Treatment regimens changed dramatically over the study period, with an increase in combination prophylaxis and a decrease in the use of sdNVP. Uptake of DBS PCR more than tripled over the period of study for the three regions surveyed. Our study demonstrates significant reductions in MTCT of HIV-1 in three regions of Tanzania coincident with increased use of more effective PMTCT interventions. The changes we demonstrate for the period of 2008-2010 occurred prior to major changes in WHO PMTCT guidelines.PLoS ONE 01/2014; 9(2):e88679. · 3.73 Impact Factor -
Article: Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.
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ABSTRACT: The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.PLoS Neglected Tropical Diseases 07/2013; 7(7):e2324. · 4.57 Impact Factor -
Article: Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania.
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ABSTRACT: To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of fever. Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adolescents and adults, the remainder were infants and children. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adolescents and adults, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing an aetiologic diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections.Clinical radiology 06/2013; · 1.65 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Introduction Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. Materials and methods We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. Results After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14–3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00–2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90–2.53, and OR 1.44, 95 % CI 0.90–2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. Conclusions While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.Clinical and Translational Oncology 06/2013; DOI 10.1007/s12094-013-1067-4. · 1.28 Impact Factor - JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2013; 62(2):e55-e57. · 4.65 Impact Factor
Article: Cancer registration needs assessment at a tertiary medical centre in Kilimanjaro, Tanzania.
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ABSTRACT: Cancer burden is increasing in Africa more than in any other continent, but population-based tracking of cancer incidence is incomplete. Cancer registries can improve understanding of cancer incidence. To assess organizational readiness to sustain registry development, we conducted a survey assessing change efficacy, resource availability and change commitment at the Kilimanjaro Christian Medical Centre (KCMC), an academic hospital in Moshi, Tanzania. Fifty-two surveys were returned (80% response rate). There was strong reliability among change efficacy and commitment survey items, with Cronbach's alphas of 0.93 and 0.77, respectively. Clinicians, nurses and administrators conveyed similar responses regarding change efficacy. Clinicians had similar responses for change commitment. Echoing opinion in many low- and middle-income countries, approximately one-third of respondents indicated there were no funds to maintain the registry, and funds were not obtainable. For most resources, respondents felt that resources were sufficient or attainable. Respondents were generally confident and committed to registry implementation. Lessons learned at KCMC may be more broadly relevant.World health & population 01/2013; 14(2):12-23. - [show abstract] [hide abstract]
ABSTRACT: Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. IMPACT STATEMENT: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress.PLoS ONE 01/2013; 8(2):e56325. · 3.73 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a ≥ 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ≥ 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with ≥ 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio [OR] 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania.The American journal of tropical medicine and hygiene 10/2012; · 2.53 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Disseminated tuberculosis is a major health problem in countries where generalized human immunodeficiency virus (HIV) infection epidemics coincide with high tuberculosis incidence rates; data are limited on patient outcomes beyond the inpatient period. We enrolled consecutive eligible febrile inpatients in Moshi, Tanzania, from 10 March 2006 through 28 August 2010; those with Mycobacterium tuberculosis bacteremia were followed up monthly for 12 months. Survival, predictors of bacteremic disseminated tuberculosis, and predictors of death were assessed. Antiretroviral therapy (ART) and tuberculosis treatment were provided. A total of 508 participants were enrolled; 29 (5.7%) had M. tuberculosis isolated by blood culture. The median age of all study participants was 37.4 years (range, 13.6-104.8 years). Cough lasting >1 month (odds ratio [OR], 13.5; P< .001), fever lasting >1 month (OR, 7.8; P = .001), weight loss of >10% (OR, 10.0; P = .001), lymphadenopathy (OR 6.8; P = .002), HIV infection (OR, undefined; P < .001), and lower CD4 cell count and total lymphocyte count were associated with bacteremic disseminated tuberculosis. Fifty percent of participants with M. tuberculosis bacteremia died within 36 days of enrollment. Lower CD4 cell count (OR, 0.88; P = .049) and lower total lymphocyte count (OR, 0.76; P = .050) were associated with death. Magnitude of mycobacteremia tended to be higher among those with lower CD4 cell counts, but did not predict death. In the era of free ART and access to tuberculosis treatment, almost one half of patients with M. tuberculosis bacteremia may die within a month of hospitalization. Simple clinical assessments can help to identify those with the condition. Advanced immunosuppression predicts death. Efforts should focus on early diagnosis and treatment of HIV infection, tuberculosis, and disseminated disease.Clinical Infectious Diseases 04/2012; 55(2):242-50. · 9.37 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs). An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000 copies/ml. Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100 mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r. Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400 copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40 copies/ml and 30 had levels 40-200 copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400 copies/ml. In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.AIDS (London, England) 03/2012; 26(11):1345-54. · 4.91 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating.The American journal of tropical medicine and hygiene 01/2012; 86(1):171-7. · 2.53 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.Infectious Agents and Cancer 11/2011; 6(1):20. - [show abstract] [hide abstract]
ABSTRACT: The importance of Q fever, spotted fever group rickettsiosis (SFGR), and typhus group rickettsiosis (TGR) as causes of febrile illness in sub-Saharan Africa is unknown; the putative role of Q fever as a human immunodeficiency virus (HIV) coinfection is unclear. We identified febrile inpatients in Moshi, Tanzania, from September 2007 through August 2008 and collected acute- and convalescent-phase serum samples. A ≥4-fold increase in immunoglobulin (Ig) G immunfluorescence assay (IFA) titer to Coxiella burnetii phase II antigen defined acute Q fever. A ≥4-fold increase in IgG IFA titer to Rickettsia conorii or Rickettsia typhi antigen defined SFGR and TGR, respectively. Among 870 patients, 483 (55.5%) were tested for acute Q fever, and 450 (51.7%) were tested for acute SFGR and TGR. Results suggested acute Q fever in 24 (5.0%) patients and SFGR and TGR in 36 (8.0%) and 2 (0.5%) patients, respectively. Acute Q fever was associated with hepato- or splenomegaly (odds ratio [OR], 3.1; P = .028), anemia (OR, 3.0; P = .009), leukopenia (OR, 3.9; P = .013), jaundice (OR, 7.1; P = .007), and onset during the dry season (OR, 2.7; P = .021). HIV infection was not associated with acute Q fever (OR, 1.7; P = .231). Acute SFGR was associated with leukopenia (OR, 4.1; P = .003) and with evidence of other zoonoses (OR, 2.2; P = .045). Despite being common causes of febrile illness in northern Tanzania, Q fever and SFGR are not diagnosed or managed with targeted antimicrobials. C. burnetii does not appear to be an HIV-associated co-infection.Clinical Infectious Diseases 08/2011; 53(4):e8-15. · 9.37 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: We enrolled consecutive febrile admissions to two hospitals in Moshi, Tanzania. Confirmed leptospirosis was defined as a ≥ 4-fold increase in microscopic agglutination test (MAT) titer; probable leptospirosis as reciprocal MAT titer ≥ 800; and exposure to pathogenic leptospires as titer ≥ 100. Among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. Of 832 patients with ≥ 1 serum sample available, 30 (3.6%) had probable leptospirosis and an additional 277 (33.3%) had evidence of exposure to pathogenic leptospires. Among those with leptospirosis the most common clinical diagnoses were malaria in 31 (44.3%) and pneumonia in 18 (25.7%). Leptospirosis was associated with living in a rural area (odds ratio [OR] 3.4, P < 0.001). Among those with confirmed leptospirosis, the predominant reactive serogroups were Mini and Australis. Leptospirosis is a major yet underdiagnosed cause of febrile illness in northern Tanzania, where it appears to be endemic.The American journal of tropical medicine and hygiene 08/2011; 85(2):275-81. · 2.53 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined. A total of 467 patients were enrolled whose median age was 2 years (range 2 months-13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.Tropical Medicine & International Health 04/2011; 16(7):830-7. · 2.94 Impact Factor -
Article: A cost-effectiveness analysis of alternative HIV retesting strategies in sub-saharan Africa.
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ABSTRACT: Guidelines in sub-Saharan Africa on when HIV-seronegative persons should retest range from never to annually for lower-risk populations and from annually to every 3 months for high-risk populations. We designed a mathematical model to compare the cost-effectiveness of alternative HIV retesting frequencies. Cost of HIV counseling and testing, linkage to care, treatment costs, disease progression, and mortality, and HIV transmission are modeled for three hypothetical cohorts with posited annual HIV incidence of 0.8%, 1.3%, and 4.0%, respectively. The model compared costs, quality-adjusted life-years gained, and secondary infections averted from testing intervals ranging from 3 months to 30 years. Input parameters from sub-Saharan Africa were used and explored in sensitivity analyses. Accounting for secondary infections averted, the most cost-effective testing frequency was every 7.5 years for 0.8% incidence, every 5 years for 1.3% incidence, and every 2 years for 4.0% incidence. Optimal testing strategies and their relative cost-effectiveness were most sensitive to assumptions about HIV counseling and testing and treatment costs, rates of CD4 decline, rates of HIV transmission, and whether tertiary infections averted were taken into account. While higher risk populations merit more frequent HIV testing than low risk populations, regular retesting is beneficial even in low-risk populations. Our data demonstrate benefits of tailoring testing intervals to resource constraints and local HIV incidence rates.JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2011; 56(5):443-52. · 4.65 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. we enrolled consecutive admitted patients aged ≥ 13 years with oral temperature of ≥ 38.0°C during 1 year in Moshi, Tanzania. A standardized clinical history and physical examination was done and hospital outcome recorded. HIV antibody testing, aerobic and mycobacterial blood cultures, and malaria film were performed. HIV-infected patients also received serum cryptococcal antigen testing and CD4(+) T lymphocyte count (CD4 cell count). of 403 patients enrolled, the median age was 38 years (range, 14-96 years), 217 (53.8%) were female, and 157 (39.0%) were HIV-infected. Of HIV-infected patients, the median CD4 cell count was 98 cells/μL (range, 1-1,105 cells/ μL), 20 (12.7%) were receiving ART, and 29 (18.5%) were receiving trimethoprim-sulfamethoxazole prophylaxis. There were 112 (27.7%) patients who had evidence of invasive disease, including 26 (23.2%) with Salmonella serotype Typhi infection, 24 (21.4%) with Streptococcus pneumoniae infection, 17 (15.2%) with Cryptococcus neoformans infection, 12 (10.7%) with Mycobacterium tuberculosis complex infection, 8 (7.1%) with Plasmodium falciparum infection, and 7 (6.3%) with Escherichia coli infection. HIV infection was associated with M. tuberculosis and C. neoformans bloodstream infection but not with E. coli, S. pneumoniae, or P. falciparum infection. HIV infection appeared to be protective against Salmonella. Typhi bloodstream infection (odds ratio, .12; P = .001). while Salmonella Typhi and S. pneumoniae were the most common causes of invasive infection overall, M. tuberculosis and C. neoformans were the leading causes of bloodstream infection among HIV-infected inpatients in Tanzania in the ART era. We demonstrate a protective effect of HIV against Salmonella. Typhi bloodstream infection in this setting. HIV co-infections continue to account for a large proportion of febrile admissions in Tanzania.Clinical Infectious Diseases 02/2011; 52(3):341-8. · 9.37 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations.PLoS ONE 01/2011; 6(1):e16488. · 3.73 Impact Factor - [show abstract] [hide abstract]
ABSTRACT: This study examines the association between microalbuminuria and the development of proteinuria among HIV-infected persons. A total of 948 subjects provided urine samples for albumin, protein and creatinine measurements semiannually. Microalbuminuria was defined as an albumin-to-creatinine ratio of >30 mg/g. Proteinuria was defined as a protein-to-creatinine ratio of > or =0.350 mg/mg. The progression from microalbuminuria to proteinuria was described. At baseline, 69.4% of the subjects had no detectable proteinuria, 20.2% had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria and proteinuria were more likely to be black (P=0.02), have lower CD4 cell counts (P=0.02 comparing subjects without abnormal urine protein excretion to subjects with microalbuminuria; P=0.0001 comparing subjects with microalbuminuria to subjects with proteinuria), and have a higher HIV RNA level (P=0.08 and 0.04, respectively). Among 658 subjects with normal urine protein, 82.7% continued to have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed proteinuria. Subjects without baseline proteinuria (i.e. either normal protein excretion or microalbuminuria) who developed proteinuria were more likely to have microalbuminuria (P=0.001), a lower CD4 cell count (P=0.06), and a higher plasma HIV RNA (P=0.03) than those who did not progress to proteinuria. In multivariate analysis, only microalbuminuria remained associated with the development of proteinuria (odds ratio 2.9; 95% confidence interval 1.5, 5.5; P=0.001). Microalbuminuria predicts the development of proteinuria among HIV-infected persons. Because proteinuria has been linked to poorer outcomes, strategies to affect microalbuminuria should be tested.HIV Medicine 08/2010; 11(7):419-26. · 3.16 Impact Factor
Publication Stats
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Duke University Medical Center
- • Department of Medicine
- • Division of Infectious Diseases
- • Department of Pediatrics
- • Department of Surgery
Durham, NC, United States
Duke University
Durham, North Carolina, United States
Kilimanjaro Christian Medical Centre
Moschi, Kilimanjaro, Tanzania
Massachusetts General Hospital
Boston, Massachusetts, United States
Tumaini University (TU)
Aruscha, Arusha, Tanzania -
University of Pittsburgh
- School of Medicine
Pittsburgh, PA, United States


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oh my god i am so excited. also it is my literal life dream to get my song on the soundtrack for the movie. *prays rlly hard* *also hints that...
Just searched the "kidwithachalkboard" tag and you all so freaking cute I can't stand it. I even made some tumblr crushes lists?! What is life.
Oh that's a thought! I think Luke is probably the better cook, but I'm the better baker :)


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Check out these great photos of the ribbon cutting ceremony at Sandvoort […]
by Amby Burfoot , Bart Yasso , Jennifer Van Allen
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7 books to get you ready for spring break
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Yeah, yeah, we've all been there, done that. This year, let's put that embarrassment behind us and own our monthly supply trip. OK, maybe not, but we can at least find a better way to get the job done, right? Here are our three favorite strategies for snagging period products on the sly.
Strategy #1: Text Mom, stat
You know you need them, you just don't want to say it out loud, right? Solution: Do it by text. As soon as you make it to your locker in the a.m. (and no pesky boys are looking over your shoulder), send Mom a quick text (and be sure you're actually sending it to Mom before ya hit "send"!) to let her know you need them, like, now. Or, you know, after school. Done!
Strategy #2: Order 'em online
A handy new web start-up called Le Parcel has come up with an ingenious service: For $15 a month, they will send you your favorite product (choose from Playtex, Tampax or Kotex, and tampons, pads and panty liners), plus chocolate and a prezzie to perk ya up during your period. You can even sync the shipping so ya get your goodies when your period is due.
Strategy #3: Be bold as brass
POSTED IN period 101, be period prepared, tampons, pads
Acid reflux is only a problem for adults.
It Takes Two: Win, read and review!
Win, read and review an exclusive, advanced reading copy of It Takes Two: A Whole New Ball Game by Belle Payton...and you might be featured by GL! CLICK HERE to enter


text:
Comment: When greed breaks stuff (Score 2) 164
All the people who warned them that they will cause permanent micro- and macro- disasters all over the world have been ignored. Due to greed. Let them be proud of their achievement.
All the people who warned them that they will cause permanent micro- and macro- disasters all over the world have been ignored. Due to greed. Let them be proud of their achievement.
Are you sure it's really a honest acquisition and not a lame attempt to use a portion of your huge pile of money just to monopolize a market you're afraid of slowly losing?
I fail to see how Bitcoin is private and confidential. All the transactions are public (inherently by design). And if you buy bitcoins somewhere with your CC or paypal or bank, it is possible to link the bitcoins to your name.
If you buy them with cash, you could as well buy one of those cash coupons that porn sites might accept too. Then, you gain TRUE anonymity and, as a bonus, you and the seller avoid the massive volatility of the currency (100x decrease/increase in value over a day).
Maybe in the US where you can settle even criminal offenses out of court if you have the cash.
But in the EU, if you kill someone with a car, you HAVE TO be sued by the government because criminal offenses cannot be settled out of court here.
RTFA: The former US National Security Agency worker would testify by interactive video link from Russia, where he has been granted temporary asylum.
Heh. Would be funny if the packets were routed via the US and patriotically "deep-inspected" by the NSA.
Using facebook in any way + caring about your privacy
= mutually exclusive.
Just, please, this time, try to be more careful about who joins your working groups. And especially what their true intentions are.
Sometimes when someone tries to "simplify deployment" or "offers insight to prevent user confusion", etc., you may want to think twice. History repeats itself, you know.
Only an idiot would run a browser on an OS with unpatched vulnerabilities. Windows XP will not get any security issues fixed after April 2014. If you ignore those simple facts, you deserve becoming a part of a botnet, sending your passwords and credit card numbers to the botmaster.
Problem: Paranoia
Solution: None
A very interesting piece of info is at the bottom of TFA:
since readers were allowed to make comments without registering their names, the identity of the authors would have been extremely difficult to establish. Making Delfi legally responsible for the comments was therefore practical, said the court. It was also reasonable, because the news portal received commercial benefit from comments being made.
I don't see how that is immune to the chicken-and-egg problem. In other words, unless you write your own C compiler in raw CPU instructions (machine code), you cannot trust ANY compiler binaries.
The guy calls himself cryptographer, but he doesn't know what he's talking about.
Hashes, and also any ideal random oracles, have only (n/2) security due to so called birthday paradox limit.
That's why SHA-512 has only 256-bit security. This is not weakening of the hash in any form. It is a property of any hash or RNG.
What the slides show is that they want to reduce clutter in reducing dozen options into two options. One high-security (256-bit security) and another fast, medium-security.
Your personal *dream* favorites. You wouldn't survive there more than a few weeks, bud. Because, as you said, "you will not be of interest" there (for instance, when you break a bone and need help, or food, or protection from bandits...)
If you have anything above Top Secret to hide, good luck to you, you'll need it (either this, or maybe you're a little delusional).
Until they are served with a secret order telling them (i) to install key escrow backdoor and/or (ii) until NSA starts implanting torjans onto the suspects' computers (like FBI did with some of the Tor users recently, exploiting an unpatched vulnerability in the TorBrowser - http://yro.slashdot.org/story/13/08/04/2054208/half-of-tor-sites-compromised-including-tormail ).
Doubt is a pain too lonely to know that faith is his twin brother. - Kahlil Gibran


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CARACAS, Venezuela —
Venezuelan opposition leader Henrique Capriles announced Sunday night that he will run in elections to replace Hugo Chavez, launching what many consider a doomed candidacy with a no-holds-barred attack against a government he said had coldly betrayed Venezuelans' trust.
Capriles slammed the government in his announcement for using Chavez's death to push the candidacy of Nicolas Maduro, who was sworn in as acting leader Friday. He also called top military brass an "embarrassment" for publicly supporting Maduro, although the constitution forbids the military from taking political sides.
"Don't fool yourselves that you're the good and we're the bad," the 40-year-old candidate said to the government. "No, you're no better than us. I don't play with death. I don't play with pain."
With a picture of Chavez behind him, Maduro appeared on TV after the speech to respond to what he said was "the losing, miserable candidate" who had dishonored the late president. He called Capriles a "fascist" trying to provoke violence and a coup against the state.
"We reject an infamy that you plan to hurl and the words you've said about the crystalline, pure image of Commander Chavez," Maduro said. "Enough of the offenses, sir!"
Capriles, who is governor of Venezuela's biggest state, acknowledged that he faces tough odds against an official candidate in control of vast public resources who he said has the backing of the country's electoral commission.
"As one person said today, 'Capriles, they are taking you to a slaughterhouse. Are you going to be lowered into its meat grinder?"' he said.
Capriles said, however, that he had to fight for the whole country.
"How am I not going to fight?" he said. "How are we not going to fight? This is not Capriles' fight. This is everybody's fight."
In some districts of the capital, people launched fireworks, shouted and honked horns as Capriles announced he would run.
Capriles also laid out what could be main themes of his campaign, bemoaning high crime and poverty as well as the government's decision to devalue the currency by more than 30 percent.
Venezuela's election commission has set the vote for April 14, with formal campaigning to start just 12 days earlier.
Maduro has already announced his intention to run as the candidate of Chavez's socialist party. On Sunday he also picked up the support of Venezuela's small communist party. He's expected to file election papers on Monday.
In his response, Maduro matched Capriles in the heated rhetoric, calling his opponents "oligarchs" while praising Chavez as "the chief redeemer." He also said he reserved the right to use legal means to defend the honor of Chavez and his family.
At the same time, he repeatedly asked Venezuelans to stay peaceful.
"We have to continue to rise above every provocation with peace, peace, peace and peace," Maduro said. "Respect, respect, respect."
Opposition critics have called Maduro's ascension unconstitutional, noting the charter designates the National Assembly president as acting leader if a president-elect cannot be sworn in.
Capriles faced a stark choice in deciding whether to compete in the vote, which most analysts say he is sure to lose amid a frenzy of sympathy and mourning for the dead president.
Some say a second defeat for Capriles just six months after he lost last year's presidential vote to Chavez could derail his political career. But staying on the sidelines would have put in jeopardy his leadership of the opposition.
Analysts predict the next five weeks will see a spike in the nasty, heated rhetoric that began even before Chavez's death Tuesday after a nearly two-year fight with cancer.
Political consultant Oswaldo Ramirez, who is advising the Capriles campaign, said the candidate must strike a balance between criticizing the failures of Chavez's government and Maduro's role in it, without being seen as attacking the late president.
"He can't speak badly of Chavez, because this feeling on the street is still in full bloom," Ramirez said.
Public opinion was as divided as always Sunday in a country that became dramatically more polarized during Chavez's 14-year rule.
"It's not fair," said Jose Mendez, a 54-year-old businessman of the choice the opposition leader faces. "(Maduro) has an advantage, because of everything they have done since Chavez's death, all the sentiment they've created ... But the guy has nothing. He can't hold a candle to Chavez."
But Ramon Romero said the opposition was just making excuses, and had no chance of victory in any case.
"Now their odds are even worse," said the 64-year-old waiter and staunch Chavez supporter. "They don't care about anyone, and we (the voters) have been lifted out of darkness."
Associated Press writers Jack Chang, Frank Bajak, Paul Haven and E. Eduardo Castillo contributed to this report.
State, national, world
Venezuelan opposition leader to run for president
- State, national, world
4 dead in New Jersey fire; mix-up delayed response
The fire swept through part of a block of row houses. Authorities recovered two bodies by late morning, and brought out two other bodies later in the day.
Casting Jesus: Did he really look like Brad Pitt?
"We not only found Jesus, we found 'Hot Jesus,'" Oprah Winfrey told actor Diogo Morgado in a TV interview, referring to a Twitter hashtag about the actor.
Wake up and smell the bacon ... with a bacon app
Oscar Mayer says it has created a bacon-scented app for the iPhone, developed by the Madison-based company's Institute for the Advancement of Bacon.
Oklahoma House approves triggered tax cuts plan
The House voted 57-34 for the bill that includes triggers for both cuts that would first require revenue collections to grow by enough to offset the lost revenue to the state. Because of that provision, the earliest that either tax cut would take effect is Jan. 1, 2016.
Okla. House passes measure to expand CNG stations
Rep. Josh Cockroft, R-Tecumseh, says Oklahoma Department of Transportation saved about $32,690 a month after converting 174 vehicles to compressed natural gas.
Oklahoma Senate kills pickup passenger bill
The Senate voted 26-10 against the measure Thursday. Its author, Democratic Sen. Earl Garrison of Muskogee, kept the measure alive by announcing plans to reconsider the vote next week to apply only to children.
Oklahoma kids get helmets for tornado protection
Moore Helmets for Schools, a group of volunteers headed by the mother of a Briarwood Elementary School student who survived the deadly May 20 tornado, has raised $250,000 to pay for skating helmets and storage bins.
Michigan charges Chesapeake with bid-rigging
In a statement, the attorney general's office said it suspects collusion was responsible for a steep drop in the price of drilling rights auctions in Michigan.
3.9-magnitude earthquake recorded in Edmond
Police say there are no reports of damage or injury but that there were several calls from people who felt the quake.
Pro-Common Core Okla. group delivers petition
The Expect More OK! Coalition delivered the online petition to lawmakers Wednesday.
- More State, national, world Headlines
4 dead in New Jersey fire; mix-up delayed response


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COMMERCIAL DESCRIPTION Strong-style India Pale Ale, deep copper in color witha a big, malty, hoppy palate and dry hopped with Centennial & Antanum for a spicy, citrus aroma. What better name for a big, strong beer than one of the biggest, strongest weapons of the Revolutionary War - the cannonball.
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Fragrance Hotel - Sunflower
Distance from hotel to: Kallang MRT Station - 0.68km, Singapore Flyer - 2.9km, Raffles City Shopping Area - 3.3km, Esplanade Theatres On Bay - 3.4km, Orchard Road Shopping Belt - 3.9km, Central Business District - 4.4km, Airport - 13.8km.
This Hotel is uniquely located in Geylang which is surrounded by many local famous eateries, fresh fruit stalls (Sims Avenue), temples and prewar houses. The other attraction is the 'Red Light District' which enhances the interesting side of Geylang.