Grace E Kissling

National Institute of Environmental Health Sciences, Durham, North Carolina, United States

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Publications (145)543.79 Total impact

  • David B Resnik · J.L. Ariansen · Jaweria Jamal · Grace E Kissling ·
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    ABSTRACT: Purpose: Institutional conflicts of interest (ICOIs) occur when the institution or leaders with authority to act on behalf of the institution have conflicts of interest (COIs) that may threaten the objectivity, integrity, or trustworthiness of research because they could impact institutional decision making. The purpose of this study was to gather and analyze information about the ICOI policies of the top 100 U.S. academic research institutions, ranked according to total research funding. Method: From May-June 2014, the authors attempted to obtain ICOI policy information for the top 100 U.S. academic research institutions from publicly available Web sites or via e-mail inquiry. If an ICOI policy was not found, the institutions' online COI policies were examined. Data on each institution's total research funding, national funding rank, public versus private status, and involvement in clinical research were collected. The authors developed a coding system for categorizing the ICOI policies and used it to code the policies for nine items. Interrater agreement and P values were assessed. Results: Only 28/100 (28.0%) institutions had an ICOI policy. ICOI policies varied among the 28 institutions. Having an ICOI policy was positively associated with total research funding and national funding ranking but not with public versus private status or involvement in clinical research. Conclusions: Although most U.S. medical schools have policies that address ICOIs, most of the top academic research institutions do not. Federal regulation and guidance may be necessary to encourage institutions to adopt ICOI policies and establish a standard form of ICOI review.
    Academic medicine: journal of the Association of American Medical Colleges 11/2015; DOI:10.1097/ACM.0000000000000980 · 2.93 Impact Factor
  • C J Willson · G P Flake · R C Sills · G E Kissling · M F Cesta ·
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    ABSTRACT: o-Nitroanisole is an intermediate in the manufacture of azo dyes. In a National Toxicology Program stop-exposure study, o-nitroanisole induced hyperplasia, papillomas, and papillary carcinomas in the urinary bladder of Fischer 344/N rats. o-Nitroanisole was investigated since occupational or environmental exposure to aniline and azo dyes is a risk factor for urinary bladder cancer in humans. The current study describes the morphology of urinary bladder neoplasms seen in rats with respect to those observed in humans. This study also evaluated immunohistochemical expression of the cell cycle-related proteins cyclin D1 and p53 and the differentiation markers cytokeratin 20 and uroplakin III in hyperplastic (n = 11) and neoplastic (n = 6 papillomas, n = 11 carcinomas) lesions of the urinary bladder epithelium from rats treated with o-nitroanisole and in normal (n = 6) urinary bladders from untreated rats. The tumors observed were more similar to the papillary type rather than the muscle-invasive type of urinary bladder cancer in humans. The preneoplastic and neoplastic lesions observed suggest progression from hyperplasia to papilloma to papillary carcinoma. With neoplastic progression (hyperplasia to papilloma to carcinoma), cyclin D1 immunoreactivity progressively increased in intensity, percentage of cells staining, and distribution. Overexpression of p53 was not found. Cytokeratin 20 staining decreased in superficial cells, while uroplakin III staining increased in intermediate and basal cells with progression from hyperplasia to carcinoma. The results are consistent with increased cell cycle dysregulation or proliferation (cyclin D1), decreased differentiation (cytokeratin 20), and abnormal differentiation (uroplakin III) as lesions progress toward malignancy. © The Author(s) 2015.
    Veterinary Pathology 08/2015; DOI:10.1177/0300985815603432 · 1.87 Impact Factor
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    ABSTRACT: Bisphenol A (BPA) is a high production volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products including cash register receipt paper; however little is known about exposure of cashiers to BPA and alternative compounds in receipt paper. To determine if handling receipt paper results in measurable absorption of BPA or the BPA alternatives, bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP). Cashiers (n = 77) and non-cashiers (n=25) were recruited from the Raleigh-Durham-Chapel Hill region of North Carolina during 2011-2013. Receipts were analysed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2h after completing a shift) were compared with pre-shift samples (collected ≥ 24 hours after a work shift). Urine levels in cashiers were compared to levels from non-cashiers. Each receipt contained 1-2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. Mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as increase after a shift, but the mean post-shift concentration was significantly higher than in non-cashiers. BPSIP was detected more frequently in urine of cashiers handling BPSIP receipts compared to non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently. Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP.
    Environmental Health Perspectives 08/2015; DOI:10.1289/ehp.1409427 · 7.98 Impact Factor
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    ABSTRACT: Mice exposed to high levels of arsenic in utero are more susceptible to tumors such as hepatic and pulmonary carcinoma when they reach adulthood. However, effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear. We evaluated the effect of in utero exposure to inorganic arsenic at the EPA drinking water standard (10 ppb) and tumor-inducing level (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reach adulthood. Pregnant CD-1 mice were exposed to sodium arsenite (0, 10 ppb, or 42.5 ppm) in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) of the exposed females in adulthood. Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10 ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10 ppb and 42.5 ppm groups, exposed females had significantly higher body weight gain, body fat content, and glucose intolerance. Our findings reveal unexpected effects that in utero exposure to arsenic at a human relevant low dose and a tumor-inducing level leads to early onset of vaginal opening and obesity in female CD-1 mice.
    Environmental Health Perspectives 08/2015; DOI:10.1289/ehp.1509703 · 7.98 Impact Factor
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    David B Resnik · Elizabeth Wager · Grace E Kissling ·
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    ABSTRACT: This study gathered information about the retraction policies of the top 200 scientific journals, ranked by impact factor. Editors of the top 200 science journals for the year 2012 were contacted by email. One hundred forty-seven journals (74%) responded to a request for information. Of these, 95 (65%) had a retraction policy. Of journals with a retraction policy, 94% had a policy that allows the editors to retract articles without authors' consent. The majority of journals in this sample had a retraction policy, and almost all of them would retract an article without the authors' permission.
    Journal of the Medical Library Association JMLA 07/2015; 103(3):136-9. DOI:10.3163/1536-5050.103.3.006 · 0.99 Impact Factor
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    ABSTRACT: Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA. To reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration. We exposed six men and eight women to 100μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates. Mean serum total (unconjugated and conjugated) d6-BPA Cmax of 1711nM (390ng/ml) was observed at Tmax of 1.1±0.50h. Unconjugated d6-BPA appeared in serum within 5-20min of dosing with a mean Cmax of 6.5nM (1.5ng/ml) observed at Tmax of 1.3±0.52h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48h in some subjects at concentrations near the LOD (0.001-0.002ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4±2.0h and 6.2±2.6h, respectively. Recovery of total administered d6-BPA in urine was 84-109%. Most subjects (10 of 14) excreted >90% as metabolites within 24h. Using more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24h. Published by Elsevier Ltd.
    Environment international 06/2015; 83:107-115. DOI:10.1016/j.envint.2015.06.008 · 5.56 Impact Factor
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    ABSTRACT: Rodent lung tumors are morphologically similar to a subtype of human lung adenocarcinomas. The objective of this study was to evaluate Kirsten rat sarcoma oncogene homolog (Kras), epidermal growth factor receptor (Egfr), and tumor protein 53 (Tp53) mutations, which are relevant to human lung cancer, in cobalt metal dust (CMD)-induced alveolar/bronchiolar tumors of B6C3F1/N mice and F344/NTac rats. Kras mutations were detected in 67% (mice) and 31% (rats) of CMD-induced lung tumors and were predominantly exon 1 codon 12 G to T transversions (80% in mice and 57% in rats). Egfr mutations were detected in 17% (both mice and rats) of CMD-induced lung tumors and were predominantly in exon 20 with 50% G to A transitions (mice and rats). Tp53 mutations were detected in 19% (mice) and 23% (rats) of CMD-induced lung tumors and were predominant in exon 5 (mice, 69% transversions) and exon 6 (rats, all transitions). No mutations were observed for these genes in spontaneous lung tumors or normal lungs from untreated controls. Ames assay indicated that CMD is mutagenic in the absence but not in the presence of S9 mix. Thus, the mutation data (G to T transversions) and Ames assay results suggest that oxidative damage to DNA may be a contributing factor in CMD-induced pulmonary carcinogenesis in rodents. © 2015 by The Author(s).
    Toxicologic Pathology 06/2015; 43(6). DOI:10.1177/0192623315581192 · 2.14 Impact Factor
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    David B Resnik · Lisa M Rasmussen · Grace E Kissling ·
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    ABSTRACT: Research misconduct is an international concern. Misconduct policies can play a crucial role in preventing and policing research misconduct, and many institutions have developed their own policies. While institutional policies play a key role in preventing and policing misconduct, national policies are also important to ensure consistent promulgation and enforcement of ethical standards. The purpose of this study was to obtain more information about research misconduct policies across the globe. We found that twenty-two of the top forty research and development funding countries (55%) had a national misconduct policy. Four countries (18.2%) are in the process of developing a policy, and four (18.2%) have a national research ethics code but no misconduct policy. All twenty-two countries (100%) with national policies included fabrication, falsification, and plagiarism in the definition of misconduct, but beyond that there was considerable diversity. Unethical authorship was mentioned in 54.6% of the misconduct definitions, followed by unethical publication practices (36.4%), conflict of interest mismanagement (36.4%), unethical peer review (31.8%), misconduct related to misconduct investigations (27.3%), poor record keeping (27.3%), other deception (27.3%), serious deviations (22.7%), violating confidentiality (22.7%), and human or animal research violations (22.7%). Having a national policy was positively associated with research and development funding ranking and intensiveness. To promote integrity in international research collaborations, countries should seek to harmonize and clarify misconduct definitions and develop procedures for adjudicating conflicts when harmonization does not occur.
    Accountability in Research Policies and Quality Assurance 04/2015; 22(5):249-66. DOI:10.1080/08989621.2014.958218 · 0.83 Impact Factor
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    David B Resnik · Talicia Neal · Austin Raymond · Grace E Kissling ·
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    ABSTRACT: In 2000, the U.S. federal government adopted a uniform definition of research misconduct as fabrication, falsification, or plagiarism (FFP), which became effective in 2001. Institutions must apply this definition of misconduct to federally-funded research to receive funding. While institutions are free to adopt definitions of misconduct that go beyond the federal standard, it is not known how many do. We analyzed misconduct policies from 183 U.S. research institutions and coded them according to thirteen different types of behavior mentioned in the misconduct definition. We also obtained data on the institution's total research funding and public vs. private status, and the year it adopted the definition. We found that more than half (59%) of the institutions in our sample had misconduct policies that went beyond the federal standard. Other than FFP, the most common behaviors included in definitions were "other serious deviations" (45.4%), "significant or material violations of regulations" (23.0%), "misuse of confidential information" (15.8%), "misconduct related to misconduct" (14.8%), "unethical authorship other than plagiarism" (14.2%), "other deception involving data manipulation" (13.1%), and "misappropriation of property/theft" (10.4%). Significantly more definitions adopted in 2001 or later went beyond the federal standard than those adopted before 2001 (73.2% vs. 26.8%), and significantly more definitions adopted by institutions in the lower quartile of total research funding went beyond the federal standard than those adopted by institutions in the upper quartiles. Public vs. private status was not significantly associated with going beyond the federal standard.
    Accountability in Research 01/2015; 22(1):14-21. DOI:10.1080/08989621.2014.891943 · 0.83 Impact Factor
  • J K Dunnick · J M Sanders · G E Kissling · C. L. Johnson · M H Boyle · S A Elmore ·
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    ABSTRACT: Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Müllerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17β (HSD17β) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms. © 2014 by The Author(s).
    Toxicologic Pathology 12/2014; 43(4). DOI:10.1177/0192623314557335 · 2.14 Impact Factor
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    ABSTRACT: Perfluorooctanoic acid (PFOA) is a ubiquitous pollutant that causes liver toxicity in rodents, a process believed to be dependent on peroxisome proliferator-activated receptor-alpha (PPARα) activation. Differences between humans and rodents have made the human relevance of some health effects caused by PFOA controversial. We analyzed liver toxicity at 18 months following gestational PFOA exposure in CD-1 and 129/Sv strains of mice and compared PFOA-induced effects between strains and in wild type (WT) and PPARα-knockout (KO) 129/Sv mice. Pregnant mice were exposed daily to doses (0.01-5 mg/kg/BW) of PFOA from gestation days 1 to 17. The female offspring were necropsied at 18 months, and liver sections underwent a full pathology review. Hepatocellular adenomas formed in PFOA-exposed PPARα-KO 129/Sv and CD-1 mice and were absent in untreated controls from those groups and WT 129/Sv. Hepatocellular hypertrophy was significantly increased by PFOA exposure in CD-1, and an increased severity was found in WT 129/Sv mice. PFOA significantly increased nonneoplastic liver lesions in PPARα-KO mice (hepatocyte hypertrophy, bile duct hyperplasia, and hematopoietic cell proliferation). Low-dose gestational exposures to PFOA induced latent PPARα-independent liver toxicity that was observed in aged mice. Evidence of liver toxicity in PPARα-KO mice warrants further investigation into PPARα-independent pathways.
    Toxicologic Pathology 11/2014; 43(4). DOI:10.1177/0192623314558463 · 2.14 Impact Factor
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    ABSTRACT: Background: Inhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers. objective: We sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that infuence benzene-induced genotoxicity. Methods: We exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). Te study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis. Results: We observed a dose-dependent increase in benzene-induced chromosomal damage and estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice. Tis estimate is an order of magnitude below the value estimated using B6C3F1 mice. We identifed a locus on Chr 10 (31.87 Mb) that contained a pair of overexpressed sulfotransferases that were inversely correlated with genotoxicity. Conclusions: The genetically diverse DO mice provided a reproducible response to benzene exposure. Te DO mice display interindividual variation in toxicity response and, as such, may more accurately refect the range of response that is observed in human populations. Studies using DO mice can localize genetic associations with high precision. Te identifcation of sulfotransferases as candidate genes suggests that DO mice may provide additional insight into benzene-induced genotoxicity. © 2015, Public Health Services, US Dept of Health and Human Services .All rights reserved.
    Environmental Health Perspectives 11/2014; 123(3). DOI:10.1289/ehp.1408202 · 7.98 Impact Factor
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    ABSTRACT: Background: It has been proposed that cadmium (Cd) is an environmental "metalloestrogen" and that its action is mediated via the estrogen receptor (ER). Cd mimics the effects of estrogen in the rat uterus, and blood Cd concentrations positively correlate with ER levels in uteri of women with fibroids. Objectives: In the present study we explored whether Cd could stimulate proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM) cells and uterine smooth muscle cells (ht-UtSMCs) through classical interactions with ERα and ERβ, or by nongenomic mechanisms. Methods: We used estrogen response element (ERE) reporters, phosphorylated receptor tyrosine kinase arrays, Western blot analysis, estrogen binding, and cell proliferation assays to evaluate the effects of Cd on ht-UtLM cells and ht-UtSMCs. Results: Cd stimulated growth of both cell types at lower concentrations and inhibited growth at higher concentrations (≥ 50 μM). Cd did not significantly bind to ERα or ERβ, nor did it show transactivation in both cell types transiently transfected with ERE reporter genes. However, in both cells types, Cd (0.1 μM and 10 μM) activated p44/42 MAPK (ERK1/2), and a MAPK inhibitor (PD98059) abrogated Cd-induced cell proliferation. Cd in ht-UtLM cells, but not in ht-UtSMCs, activated the growth factor receptors EGFR, HGFR, and VEGF-R1 upstream of MAPK. Additional studies in ht-UtLM cells showed that AG1478, an EGFR inhibitor, abolished Cd-induced phosphorylation of EGFR and MAPK. Conclusions: Our results show that low concentrations of Cd stimulated cell proliferation in estrogen-responsive uterine cells by nongenomic activation of MAPK, but not through classical ER-mediated pathways.
    Environmental Health Perspectives 10/2014; 123(4). DOI:10.1289/ehp.1408234 · 7.98 Impact Factor
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    ABSTRACT: Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3, and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA.
    Toxicologic Pathology 10/2014; 43(4). DOI:10.1177/0192623314551841 · 2.14 Impact Factor
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    ABSTRACT: Sorbitol dehydrogenase (SDH) is a liver-specific enzyme sensitive to the detection of acute hepatocellular injury in rats; however, its usefulness has been questioned as being a highly labile enzyme. The purpose of this study was to determine the stability of serum and plasma SDH activity from both untreated rats and those treated with a single low dose injection of d-(+)-galactosamine hydrochloride, a known hepatotoxicant. After collection and initial SDH activity analysis, aliquots of serum and plasma were stored at 21°C, 4°C, and -80°C and analyzed at various time points. Serum SDH activity was stable for 4 hr at 21°C. At 4°C, serum SDH activity was stable for 24 hr, after which it significantly increased; it was not stable at -80°C. Plasma SDH activity was significantly increased by 4 hr at 21°C and 4°C, and by 48 hr at -80°C. Analysis of plasma SDH activity should occur shortly after blood collection. Analysis of serum SDH activity should occur within 4 hr of collection or stored at 4°C and measured within 24 hr. Extended storage at 4°C or -80°C for the measurement of serum or plasma SDH activity cannot be recommended due to the observed substantial elevations in SDH activity.
    Toxicologic Pathology 10/2014; DOI:10.1177/0192623314552853 · 2.14 Impact Factor
  • Michael P Waalkes · Wei Qu · Erik J Tokar · Grace E Kissling · Darlene Dixon ·

    Archive für Toxikologie 09/2014; 88(11). DOI:10.1007/s00204-014-1369-5 · 5.98 Impact Factor
  • Grace E Kissling · Joseph K Haseman · Errol Zeiger ·
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    ABSTRACT: A recent article by Gaus (2014) demonstrates a serious misunderstanding of the NTP's statistical analysis and interpretation of rodent carcinogenicity data as reported in Technical Report 578 (Ginkgo biloba) (NTP 2013), as well as a failure to acknowledge the abundant literature on false positive rates in rodent carcinogenicity studies. The NTP reported Ginkgo biloba extract to be carcinogenic in mice and rats. Gaus claims that, in this study, 4800 statistical comparisons were possible, and that 209 of them were statistically significant (p<0.05) compared with 240 (4800×0.05) expected by chance alone; thus, the carcinogenicity of Ginkgo biloba extract cannot be definitively established. However, his assumptions and calculations are flawed since he incorrectly assumes that the NTP uses no correction for multiple comparisons, and that significance tests for discrete data operate at exactly the nominal level. He also misrepresents the NTP's decision making process, overstates the number of statistical comparisons made, and ignores that fact that that the mouse liver tumor effects were so striking (e.g., p<0.0000000000001) that it is virtually impossible that they could be false positive outcomes. Gaus' conclusion that such obvious responses merely "generate a hypothesis" rather than demonstrate a real carcinogenic effect has no scientific credibility. Moreover, his claims regarding the high frequency of false positive outcomes in carcinogenicity studies are misleading because of his methodological misconceptions and errors.
    Toxicology Letters 09/2014; 237(2). DOI:10.1016/j.toxlet.2014.09.016 · 3.26 Impact Factor
  • David P Livingston · Tan D Tuong · Grace E Kissling · John M Cullen ·
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    ABSTRACT: Visualizing the interior (lumen) of a tubular structure within tissue can provide a unique perspective on anatomical organization of the tissue. Portal tracts of the liver contain several vessels and ducts in various patterns of intertwining branches and are an example of such spaces. An inexpensive method, using light microscopy and a sample of conventionally stained canine livers, was used to colorize and allow visualization of the lumens of vessels within the portal tract in three dimensions. When the colour of the background was digitally cleared and the lumen filled with a solid colour, it was possible to measure areas and volumes of the portal vein, arteries, bile ducts and lymphatics. Significant differences between vessels and ducts across lobes and gender in control samples are discussed. Differences were also found between control and mixed breed dogs and between controls and a dog that died of accidental traumatic haemorrhage. These differences are discussed in relation to visualizing lumens using images generated from a light microscope. Vessels in plants such as xylem and continuously formed spaces resulting from ice formation are other examples where this technique could be applied.
    Journal of Microscopy 09/2014; 256(3). DOI:10.1111/jmi.12171 · 2.33 Impact Factor
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    ABSTRACT: Background:Autoantibodies are of growing interest in cancer research as potential biomarkers; yet the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population, and are more prevalent in women and older adults. Here we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women. Methods:We analyzed data on reproductive history and exogenous hormone use in relation to serum ANA in 2,037 females ages 12 and older from the National Health and Nutrition Examination Survey (NHANES; 1999-2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were adjusted for age, race and poverty-income-ratio, and models were stratified by menopause status. Results:In premenopausal women ages 20 and older, ANA prevalence was associated with parity (p<0.001; parous versus nulliparous POR=2.0; 95%CI 1.2, 3.4), but in parous women ANA did not vary by number of births, age at first birth, years since last birth or breastfeeding. In postmenopausal women, ANA prevalence was associated with an older age at menarche (p=0.019; age 16-20 versus 10-12 years POR=3.0, 95%CI 1.6, 5.9), but not with parity. Oral contraceptives and estrogen therapy were not associated with a higher ANA prevalence. Conclusions:Childbearing (having had one or more births) may explain age-associated elevations in ANA prevalence seen in premenopausal women. Impact:These findings highlight the importance of considering reproductive history in studies of autoimmunity and cancer in women.
    Cancer Epidemiology Biomarkers & Prevention 08/2014; 23(11). DOI:10.1158/1055-9965.EPI-14-0429 · 4.13 Impact Factor

Publication Stats

3k Citations
543.79 Total Impact Points


  • 2004-2015
    • National Institute of Environmental Health Sciences
      • • Biostatistics Branch
      • • Cellular & Molecular Pathology Branch
      Durham, North Carolina, United States
    • National Institutes of Health
      • • Branch of Bio-statistics
      • • Division of Intramural Research
      Maryland, United States
  • 2008-2013
    • Northern Inyo Hospital
      BIH, California, United States
    • University of Cincinnati
      • Department of Biological Sciences
      Cincinnati, Ohio, United States
  • 2011
    • North Carolina Department of Health and Human Services
      Raleigh, North Carolina, United States
  • 2006
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States
    • University of Southern Mississippi
      • Gulf Coast Research Laboratory
      HBG, Mississippi, United States