James E Keen

Louisiana State University, Baton Rouge, Louisiana, United States

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Publications (77)238.82 Total impact

  • John D Keen · James Keen
    No preview · Article · Mar 2012 · Archives of internal medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Cattle are a major reservoir for Shiga toxin-producing Escherichia coli O157 (STEC O157) and harbor multiple genetic subtypes that do not all associate with human disease. STEC O157 evolved from an E. coli O55:H7 progenitor; however, a lack of genome sequence has hindered investigations on the divergence of human- and/or cattle-associated subtypes. Our goals were to 1) identify nucleotide polymorphisms for STEC O157 genetic subtype detection, 2) determine the phylogeny of STEC O157 genetic subtypes using polymorphism-derived genotypes and a phage insertion typing system, and 3) compare polymorphism-derived genotypes identified in this study with pulsed field gel electrophoresis (PFGE), the current gold standard for evaluating STEC O157 diversity. Using 762 nucleotide polymorphisms that were originally identified through whole-genome sequencing of 189 STEC O157 human- and cattle-isolated strains, we genotyped a collection of 426 STEC O157 strains. Concatenated polymorphism alleles defined 175 genotypes that were tagged by a minimal set of 138 polymorphisms. Eight major lineages of STEC O157 were identified, of which cattle are a reservoir for seven. Two lineages regularly harbored by cattle accounted for the majority of human disease in this study, whereas another was rarely represented in humans and may have evolved toward reduced human virulence. Notably, cattle are not a known reservoir for E. coli O55:H7 or STEC O157:H¯ (the first lineage to diverge within the STEC O157 serogroup), which both cause human disease. This result calls into question how cattle may have originally acquired STEC O157. The polymorphism-derived genotypes identified in this study did not surpass PFGE diversity assessed by BlnI and XbaI digestions in a subset of 93 strains. However, our results show that they are highly effective in assessing the evolutionary relatedness of epidemiologically unrelated STEC O157 genetic subtypes, including those associated with the cattle reservoir and human disease. Supplementary tables 1–5 are attached (below) as .xlsx files
    Full-text · Article · Feb 2012 · Molecular Biology and Evolution
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    Dataset: Table S1
    [Show abstract] [Hide abstract] ABSTRACT: Distribution of TMEM154 risk factors and diplotypes in matched cases-control pairs of ewes. (XLSX)
    Preview · Dataset · Jan 2012
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    Dataset: Table S4
    [Show abstract] [Hide abstract] ABSTRACT: Oligonucleotides for ovine TMEM154 PCR, RT–PCR, and DNA sequencing. (XLSX)
    Preview · Dataset · Jan 2012
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    [Show abstract] [Hide abstract] ABSTRACT: Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10(-9)). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5-1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36-3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection.
    Full-text · Article · Jan 2012 · PLoS Genetics
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    Dataset: Table S2
    [Show abstract] [Hide abstract] ABSTRACT: TMEM154 haplotype risk factor analyses in cohort studies. (XLSX)
    Preview · Dataset · Jan 2012
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    Dataset: Table S3
    [Show abstract] [Hide abstract] ABSTRACT: TMEM154 genotypes by serological status in matched case-control sheep (n = 260) and sheep in cohort studies (n = 2,705). (XLSX)
    Preview · Dataset · Jan 2012
  • John D. Keen · James E. Keen
    [Show abstract] [Hide abstract] ABSTRACT: PURPOSE Digital mammography has experienced rapid growth despite lack of cost-effectiveness (Tosteson 2008). Furthermore, the linkage to CAD risks decreased specificity from CAD induced recall exams (Fenton 2007). Economic analysis of the conversion to digital from film requires knowing the market penetration of CAD in United States (U.S.) mammography facilities and the price differentials for digital vs. film screening. METHOD AND MATERIALS Using a random sample, we conducted a telephone survey of 400, or 4.6%, of the 8651 Mammography Quality Standard Act of 1992 (MQSA) certified mammography facilities excluding U.S. territories as of August 2007. Between January and March of 2008, we called the phone number as listed in the FDA database and asked if the facility provided digital or film screening mammograms as well as technical, professional, or global cash prices. We also asked if the facility used “computer-aided detection.” We made additional calls as needed. RESULTS 367/400 or 92% of facilities provided basic responses. Overall, 238/367 or 64.8% used CAD, while 140/367 or 38.1% claimed digital technology. For digital facilities, 128 of 140 (91.4%, 85.5 to 95.5 95% CI) used CAD, while only 110 of 227 (48.5%, 41.8 to 55.2 95% CI) film-only facilities used CAD. CAD usage by digital differed significantly from film facilities (odds ratio 11.4, 5.9 to 25.0 95% CI). Only one facility had optional CAD, or 0.3%. We obtained global prices from 252/400 or 63% of facilities. For the n=98 digital, the median/mean prices were $250/$263, and for the n=154 film $176/$192, (median difference $74, p<0.0001). For the n=83 Film/CAD, the median price was $198 vs. $153 for the n=71 Film/noCAD (difference $45, p<0.004). For the 91 Dig/CAD facilities, the median price was $260 (difference with Film/noCAD $107, p <0.0001). 38 facilities provided separate CAD prices: median $43, no difference digital vs. film. Average insurance reimbursements compiled by radiology benefits manager National Imaging Associates for 2008 for Dig/CAD ($209) and Film/noCAD ($118) show a new technology premium of 77% vs. 70% for cash. CONCLUSION In 2008 over 90% of digital facilities used CAD. Dig/CAD price differentials versus film without CAD are substantial. CLINICAL RELEVANCE/APPLICATION Widespread use of CAD is likely compromising any presumed accuracy benefit from digital technology, and their combined adoption has significantly increased screening resource costs versus film.
    No preview · Conference Paper · Nov 2011
  • John D. Keen · James E. Keen
    [Show abstract] [Hide abstract] ABSTRACT: PURPOSE Between the ages of 30 and 50, about 1000 single-phase CT scans of the abdomen and pelvis will induce one future cancer over a lifetime. Surveillance Epidemiology and End Results (SEER) data show half of all cancers are lethal, so the absolute death risk is 0.5/1000, the same as the absolute benefit from 10 years of routine screening mammography. Given widespread innumeracy, we wanted to provide another perspective to promote insight into the radiation harm from the typical CT scan. METHOD AND MATERIALS We obtained the projected number of future cancers related to overall CT scan use in the United States in 2007 by age at exposure from a recent analysis. Since the cancer types were not broken down by race or sex, we calculated combined life expectancy estimates by using the gamma-mixed exponential (GAME) method, which required the United States Life Table for 2005 and SEER 10 year survival statistics for each cancer diagnosed in 1996. We assumed CT exposure at age 30 and age 50, with worst-case cancer induction at 5 years as well as at 20 years for age 50. We calculated years lost in life expectancy along with a utility loss assuming a chronic cancer state of 88% of normal health. RESULTS At age 50, the normal life expectancy is 30 years. The top five lethal cancers for life expectancy are pancreas 1.2, liver 1.8, lung 2.9, esophagus 3.5, and stomach 4.9 years. With equal cancer induction, the years lost are 13.9 and utility loss is 1.4 years. With CT weighted cancer induction, the total life loss is 16.7 years. Lung cancer contributes 30%, followed by stomach at 13%, leukemia and colon at 10%, liver at 7%, oral at 6%, bladder and brain at 5%, pancreas at 4%, and breast at 3%. For cancer induction at 5 years, the loss averages 3.6 days for every CT scan. At 20 years induction, the loss averages 8.9 years per cancer and 1.9 days per scan. At age 30 and life expectancy of 49 years, the loss averages 30 years per cancer and 7.4 days per scan. We did not discount the results. CONCLUSION For a CT scan at age 50, the percentage total life loss from a CT induced cancer at worse is 16.7/30.5 years or 54%. Every CT patient between the ages of 30 and 50 loses on average between 2 days and 1 week of life expectancy. CLINICAL RELEVANCE/APPLICATION Since the average life gain per mammogram for 40-year-old women routinely screened for 10 years is about 1 day (undiscounted), should radiologists inform their patients that CT scans take lives?
    No preview · Conference Paper · Dec 2010
  • [Show abstract] [Hide abstract] ABSTRACT: To compare methods for identification of bulls that were carriers for Tritrichomonas foetus during an outbreak on a large beef ranch and determine whether the percentage of nonpregnant cows was associated with the percentage of bulls infected with T foetus. Epidemiological study. 121 Angus and Hereford bulls (1.5 to 6 years old) and 2,960 Angus-cross cows (2.5 to 14 years old) managed as 5 herds on a Nebraska beef ranch. 3 sequential preputial scrapings collected from the bulls at 12- to 27-day intervals were cultured, and cultures were examined for live T foetus daily for 5 days. On day 5, aliquots of the culture fluid were tested by means of T foetus-specific gel and real-time PCR assays. Cows were tested for pregnancy by means of rectal palpation. For 361 preputial scrapings obtained from 121 bulls, results of culture and gel PCR assay were in close agreement. The real-time PCR assay had similar sensitivity to culture and the gel PCR assay but generated more false-positive results. Twenty-four of the 121 (19.8%) bulls were identified as infected with T foetus. For the 5 ranch herds, there was a positive linear correlation between percentage of infected bulls (range, 0% to 40%) and percentage of nonpregnant cows (range, 8.3% to 19.2%). Results suggested that a combination of culture and the gel PCR assay performed on 3 sequential preputial scrapings was the best method for identifying bulls that were carriers for T foetus during this herd outbreak.
    No preview · Article · Nov 2010 · Journal of the American Veterinary Medical Association
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    [Show abstract] [Hide abstract] ABSTRACT: Shiga-toxigenic Escherichia coli (STEC) O157 occurrence was determined along the entire gastrointestinal tract (GIT) of each of four naturally shedding cattle and at three sites in 61 slaughter cattle. STEC O157 was distributed along the entire GIT, though interanimal distribution was variable. Neither feces nor rectoanal-junction samples accurately predicted the STEC O157-negative status of any particular animal.
    Full-text · Article · Aug 2010 · Applied and Environmental Microbiology
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    [Show abstract] [Hide abstract] ABSTRACT: The intestinal microbiota of beef cattle are important for animal health, food safety, and methane emissions. This full-length sequencing survey of 11,171 16S rRNA genes reveals animal-to-animal variation in communities that cannot be attributed to breed, gender, diet, age, or weather. Beef communities differ from those of dairy. Core bovine taxa are identified.
    Full-text · Article · Jul 2010 · Applied and Environmental Microbiology
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    [Show abstract] [Hide abstract] ABSTRACT: The objectives of the study described here were (i) to investigate the dynamics of Escherichia coli O157:H7 fecal and hide prevalence over a 9-month period in a feedlot setting and (ii) to determine how animals shedding E. coli O157:H7 at high levels affect the prevalence and levels of E. coli O157:H7 on the hides of other animals in the same pen. Cattle (n = 319) were distributed in 10 adjacent pens, and fecal and hide levels of E. coli O157:H7 were monitored. When the fecal pen prevalence exceeded 20%, the hide pen prevalence was usually (25 of 27 pens) greater than 80%. Sixteen of 19 (84.2%) supershedder (>104 CFU/g) pens had a fecal prevalence greater than 20%. Significant associations with hide and high-level hide (≥40 CFU/100 cm2) contamination were identified for (i) a fecal prevalence greater than 20%, (ii) the presence of one or more high-density shedders (≥200 CFU/g) in a pen, and (iii) the presence of one or more supershedders in a pen. The results presented here suggest that the E. coli O157:H7 fecal prevalence should be reduced below 20% and the levels of shedding should be kept below 200 CFU/g to minimize the contamination of cattle hides. Also, large and unpredictable fluctuations within and between pens in both fecal and hide prevalence of E. coli O157:H7 were detected and should be used as a guide when preharvest studies, particularly preharvest intervention studies, are designed.
    Full-text · Article · Sep 2009 · Applied and Environmental Microbiology
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    [Show abstract] [Hide abstract] ABSTRACT: Cattle are a reservoir of Shiga toxin-producing Escherichia coli O157:H7 (STEC O157), and are known to harbor subtypes not typically found in clinically ill humans. Consequently, nucleotide polymorphisms previously discovered via strains originating from human outbreaks may be restricted in their ability to distinguish STEC O157 genetic subtypes present in cattle. The objectives of this study were firstly to identify nucleotide polymorphisms in a diverse sampling of human and bovine STEC O157 strains, secondly to classify strains of either bovine or human origin by polymorphism-derived genotypes, and finally to compare the genotype diversity with pulsed-field gel electrophoresis (PFGE), a method currently used for assessing STEC O157 diversity. High-throughput 454 sequencing of pooled STEC O157 strain DNAs from human clinical cases (n = 91) and cattle (n = 102) identified 16,218 putative polymorphisms. From those, 178 were selected primarily within genomic regions conserved across E. coli serotypes and genotyped in 261 STEC O157 strains. Forty-two unique genotypes were observed that are tagged by a minimal set of 32 polymorphisms. Phylogenetic trees of the genotypes are divided into clades that represent strains of cattle origin, or cattle and human origin. Although PFGE diversity surpassed genotype diversity overall, ten PFGE patterns each occurred with multiple strains having different genotypes. Deep sequencing of pooled STEC O157 DNAs proved highly effective in polymorphism discovery. A polymorphism set has been identified that characterizes genetic diversity within STEC O157 strains of bovine origin, and a subset observed in human strains. The set may complement current techniques used to classify strains implicated in disease outbreaks.
    Full-text · Article · Jun 2009 · Genome biology
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    [Show abstract] [Hide abstract] ABSTRACT: STEC O157 genotypes defined by 178 nucleotide polymorphisms.
    Preview · Dataset · May 2009
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    [Show abstract] [Hide abstract] ABSTRACT: STEC O157 genotypes defined by a minimal set of 32 nucleotide polymorphisms.
    Preview · Dataset · May 2009
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    [Show abstract] [Hide abstract] ABSTRACT: The triplicate sets of numbers on the tree represent bootstrap values from neighbor-joining, parsimony, and maximum-likelihood algorithms, respectively. Asterisks represent bootstrap values below 50%. The outer taxonomic unit genotype numbers correspond with genotype sequences recorded in Additional data file 4. The outer taxonomic units are color coded by genotype for the tir 255 T>A polymorphism and host origin. The scale bar represents substitutions per site.
    Preview · Dataset · May 2009
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    [Show abstract] [Hide abstract] ABSTRACT: Nucleotide polymorphism allele frequencies in STEC O157 strains of bovine and human origin.
    Preview · Dataset · May 2009
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    [Show abstract] [Hide abstract] ABSTRACT: STEC O157 strains used in this study with their corresponding PFGE patterns and polymorphism-derived genotypes.
    Preview · Dataset · May 2009
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    John D Keen · James E Keen
    [Show abstract] [Hide abstract] ABSTRACT: We analyzed the claim "mammography saves lives" by calculating the life-saving absolute benefit of screening mammography in reducing breast cancer mortality in women ages 40 to 65. To calculate the absolute benefit, we first estimated the screen-free absolute death risk from breast cancer by adjusting the Surveillance, Epidemiology and End Results Program 15-year cumulative breast cancer mortality to account for the separate effects of screening mammography and improved therapy. We calculated the absolute risk reduction (reduction in absolute death risk), the number needed to screen assuming repeated screening, and the survival percentages without and with screening. We varied the relative risk reduction from 10%-30% based on the randomized trials of screening mammography. We developed additional variations of the absolute risk reduction for a screening intervention, including the average benefit of a single screen, as well as the life-saving proportion among patients with earlier cancer detection. Because the screen-free absolute death risk is approximately 1% overall but rises with age, the relative risk reduction from repeated screening mammography is about 100 times the absolute risk reduction between the starting ages of 50 and 60. Assuming a base case 20% relative risk reduction, repeated screening starting at age 50 saves about 1.8 (overall range, 0.9-2.7) lives over 15 years for every 1000 women screened. The number needed to screen repeatedly is 1000/1.8, or 570. The survival percentage is 99.12% without and 99.29% with screening. The average benefit of a single screening mammogram is 0.034%, or 2970 women must be screened once to save one life. Mammography saves 4.3% of screen-detectable cancer patients' lives starting at age 50. This means 23 cancers must be found starting at age 50, or 27 cancers at age 40 and 21 cancers at age 65, to save one life. The life-saving absolute benefit of screening mammography increases with age as the absolute death risk increases. The number of events needed to save one life varies depending on the prospective screening subset or reference class. Less than 5% of women with screen-detectable cancers have their lives saved.
    Full-text · Article · May 2009 · BMC Medical Informatics and Decision Making

Publication Stats

3k Citations
238.82 Total Impact Points

Institutions

  • 2006
    • Louisiana State University
      Baton Rouge, Louisiana, United States
  • 2004-2005
    • United States Department of Agriculture
      • Agricultural Research Service (ARS)
      Washington, D. C., DC, United States
  • 2002
    • The Ohio State University
      • Department of Veterinary Preventive Medicine
      Columbus, OH, United States
  • 1995
    • Università degli Studi di Torino
      • Dipartimento di Scienze Veterinarie
      Torino, Piedmont, Italy