Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-27 (of 27 Records) |
Query Trace: Hanley A[original query] |
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Severe acute respiratory disease in American mink (Neovison vison) experimentally infected with SARS-CoV-2 (preprint)
Adney DR , Lovaglio J , Schulz JE , Yinda CK , Avanzato VA , Haddock E , Port JR , Holbrook MG , Hanley PW , Saturday G , Scott D , Spengler JR , Tansey C , Cossaboom CM , Wendling NM , Martens C , Easley J , Yap SW , Seifert SN , Munster VJ . bioRxiv 2022 24 An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, a non-transgenic model that develops severe acute respiratory disease has not been described. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding for nonstructural protein 6 in open reading frame 1a/1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID19 and as such, are uniquely suited to test viral countermeasures. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Epidemiologic and clinical features of Mpox-associated deaths - United States, May 10, 2022-March 7, 2023
Riser AP , Hanley A , Cima M , Lewis L , Saadeh K , Alarcón J , Finn L , Kim M , Adams J , Holt D , Feldpausch A , Pavlick J , English A , Smith M , Rehman T , Lubelchek R , Black S , Collins M , Mounsey L , Blythe D , Avalos MH , Lee EH , Samson O , Wong M , Stokich BD , Salehi E , Denny L , Waller K , Talley P , Schuman J , Fischer M , White S , Davis K , Caeser Cuyler A , Sabzwari R , Anderson RN , Byrd K , Gold JAW , Kindilien S , Lee JT , O'Connor S , O'Shea J , Salmon-Trejo LAT , Velazquez-Kronen R , Zelaya C , Bower W , Ellington S , Gundlapalli AV , McCollum AM , Zilversmit Pao L , Rao AK , Wong KK , Guagliardo SAJ . MMWR Morb Mortal Wkly Rep 2023 72 (15) 404-410 As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,(†) predominantly among cisgender men(§) who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox(¶) (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5). |
Severe acute respiratory disease in American mink experimentally infected with SARS-CoV-2.
Adney DR , Lovaglio J , Schulz JE , Yinda CK , Avanzato VA , Haddock E , Port JR , Holbrook MG , Hanley PW , Saturday G , Scott D , Shaia C , Nelson AM , Spengler JR , Tansey C , Cossaboom CM , Wendling NM , Martens C , Easley J , Yap SW , Seifert SN , Munster VJ . JCI Insight 2022 7 (22) An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, models that develop severe disease are still needed. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding nonstructural protein 6 in open reading frame 1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID-19 and, as such, are uniquely suited to test viral countermeasures. |
Risk assessment for o-toluidine and bladder cancer incidence
Park RM , Carreón T , Hanley KW . Am J Ind Med 2021 64 (9) 758-770 BACKGROUND: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers. METHODS: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects. RESULTS: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand. CONCLUSIONS: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk. |
Stomach cancer incidence and mortality trends among circumpolar nations
Simkin J , Nash SH , Barchuk A , O'Brien DK , Erickson AC , Hanley B , Hannah H , Corriveau A , Larsen IK , Skovlund CW , Larønningen S , Dummer TJ , Bruce MG , Ogilvie G . Cancer Epidemiol Biomarkers Prev 2021 30 (5) 845-856 BACKGROUND: Stomach cancer incidence and mortality rates are declining across circumpolar nations, but the burden may not be distributed equally across sub-populations, including Indigenous peoples. Our objective was to examine stomach cancer incidence and mortality trends across circumpolar populations. METHODS: Cancer incidence and mortality data from 1999-2016 were obtained from the Canadian Cancer Registry, Canadian Vital Statistics, CDC WONDER, NORDCAN, Northwestern Russian cancer registries and National Cancer Reports. The direct method was used to calculate ten-year rolling age-standardized incidence and mortality rates to the World (WHO 2000-2025) and 2011 Canadian standard populations. Standardized incidence rate ratios (SRRs) were calculated. Data were stratified by sex, year and region. US data were broken down by race (White; American Indian/Alaska Native (AIAN)). Race data were not available from non-US cancer registries. RESULTS: Most populations showed declining incidence and mortality rates over time. Incidence rates among Greenland males and females, Alaska AIAN males and females, and Northern Canadian both sexes were elevated compared to regional counterparts and remained stable. The largest male SRR was observed among Alaska AIAN versus Alaska Whites (SRR=3.82, 95% CI=2.71-5.37). The largest female SRR was observed among Alaska AIAN versus Alaska Whites (SRR=4.10, 95% CI=2.62-6.43). CONCLUSIONS: Despite stomach cancer incidence and mortality rates declining overall, some northern and Indigenous populations experience elevated and stable incidence and mortality rates. IMPACT: There is a need to address disparities observed among circumpolar sub-populations. Given similarities in incidence, mortality and risk factor prevalence across circumpolar regions, addressing disparities could benefit from coordinated international action. |
Manganese fractionation using a sequential extraction method to evaluate welders flux core arc welding exposures in a shipyard, structural steel and custom parts manufacturers
Hanley KW , Andrews RN , Bertke S , Carter T , Navarro K , Ashley K . Gefahrst Reinhalt Luft 2020 80 (5) 185-193 The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in flux core arc welding fume at three facilities. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Sixty-seven worker-days were monitored for either total or respirable Mn. The samples were analyzed using an experimental method to separate four Mn fractions based on chemical solubility: soluble Mn in a mild ammonium acetate solution; Mn0,2+ in 25% acetic acid; Mn3+,4+ in hydroxylamine hydrochloride in 25% acetic acid; and insoluble Mn fractions in hydrochloric/nitric acid. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.51 to 43; 2.9 to 850; 1.7 to 620; and 0.56 to 331 gm-3, for the different Mn fractions, respectively. The summation of all the total particulate Mn fractions yielded results that ranged from 16 to 1,530 g m-3. The ranges of respirable size Mn TWA concentrations were 0.27 to 75 for soluble Mn; 1.6 to 690 for Mn0,2+; 1.3 to 740 for Mn3+,4+; 0.52 to 570 for insoluble Mn; and 3.8 to 1,800 gm-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn(sum) were 56 (GSD = 4.0), 380 (GSD = 2.7), and 176 (GSD = 3.3) gm-3 for the shipyard, structural steel and custom parts facilities. Although most of the workers exposures measured were below the NIOSH Recommended Exposure Limit for Mn (1,000 gm-3), 44 welders exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 gm-3) and 46 exceeded the new respirable Mn TLV (20 gm-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding in enclosed or confined spaces. |
Ending the HIV epidemic: Contributions resulting from syphilis partner services
DiOrio D , Collins D , Hanley S . Sex Transm Dis 2020 47 (8) 511-515 BACKGROUND: There is a high level of coinfection with HIV among persons diagnosed with syphilis in the United States. Public health workers at state and local health departments help inform exposed partners to STD/HIV infections to facilitate early testing and treatment (partner services). The federal initiative, Ending the HIV Epidemic (EHE), identifies four key strategies: diagnose, treat, prevent, and respond. This study describes the contributions of syphilis partner services to the EHE strategies in a county prioritized by the EHE plan. METHODS: A retrospective record review of reported early syphilis cases (less than one year's duration) between 2016 and 2018 in the Indianapolis area was conducted to determine the extent of new HIV diagnoses, retention in HIV care, and other evidence-based HIV prevention interventions occurring after provision of syphilis partner services. RESULTS: A total of 752 partners to early syphilis were attempted to be notified of exposure. 1,457 case patients and partners received STD/HIV prevention counseling; 400 partners received STD treatment; 352 partners learned their HIV status; and 22 received new HIV diagnoses, with 68% retained in medical care and 60% virally suppressed. Two-thirds of partner services were completed within 21 days. New HIV positivity among partners to HIV-negative syphilis case patients was 3.5%, and 14% among HIV-positive syphilis case patients. CONCLUSIONS: Partner services for syphilis was an effective method of addressing the EHE strategies, resulting in persons at risk tested, STD treatment provided, PrEP referrals, and new HIV cases identified, leading to retention in medical care and viral suppression. |
Landscape analysis of breastfeeding-related physician education in the United States
Meek JY , Nelson JM , Hanley LE , Onyema-Melton N , Wood JK . Breastfeed Med 2020 15 (6) 401-411 Background: Breastfeeding is the preferred form of infant nutrition supporting optimal health of mothers and children. Research shows that medical training is deficient in preparing physicians to develop the knowledge base, clinical management skills, and attitudes to provide optimal support for breastfeeding families. We developed this project to assess the current gaps in breastfeeding education during medical training for physicians and to inform the plan to address those gaps. Materials and Methods: We conducted key informant interviews with nine professionals representing medical education, physician professional membership organizations, and ancillary stakeholders with an interest in improving physician education and training with respect to breastfeeding. Using those results, we developed and conducted a survey of physicians to identify training in breastfeeding received during medical school, residency/fellowship, and continuing medical education; confidence in managing breastfeeding; and attitudes about breastfeeding training. A total of 816 respondents completed the survey from the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists, and the American Academy of Family Physicians. Results: Gaps exist in the training of physicians in terms of knowledge base, and clinical skills in breastfeeding support as highlighted through detailed key informant interviews and physician surveys. Physicians surveyed in the disciplines of pediatrics, obstetrics and gynecology, and family medicine indicated a desire to have more breastfeeding education integrated into their training, especially addressing clinical evaluation and management of breastfeeding problems. Conclusion: The landscape analysis demonstrates that medical education in breastfeeding remains inadequate despite previous efforts to address the gaps and that physicians desire more training in breastfeeding, especially clinical skills training, to improve provider confidence and competence. The analysis provides the foundation for further efforts to develop a comprehensive plan to enhance physician education in breastfeeding. |
Support for breastfeeding physicians
Nelson JM , Onyema-Melton N , Hanley LE , Meek JY , Wood JK . J Pediatr 2019 211 225 With interest, we read the commentary by Pesch et al on the need for pediatricians to support their fellow breastfeeding colleagues.1 The American Academy of Pediatrics currently is funded by the Centers for Disease Control and Prevention to address improvements in breastfeeding-related physician education and training. As part of this project, the American Academy of Pediatrics, with input from representatives of the American College of Obstetrics and Gynecology, the American Academy of Family Physicians, and multiple other stakeholder organizations on the Project Advisory Committee developed the “Physician Education and Training on Breastfeeding Action Plan.”2 A key component of that plan is support for the breastfeeding physician. The plan included support for the revision of the Academy of Breastfeeding Medicine’s statement on breastfeeding-related educational objectives and skills needed for physicians, which includes a statement of support for breastfeeding medical students, residents, faculty, and staff.3 In addition, the American Academy of Family Physicians is leading efforts towards drafting a model policy describing how institutions can support their medical trainees (students, residents, and fellows). Finally, the Project Advisory Committee is in the process of developing a plan to create a culture of support for breastfeeding within the medical community that will emphasize support for breastfeeding physicians as a component of wellness. We agree with the authors’ conclusion that there is a need to support the breastfeeding physician. As the proportion of women physicians increases,4 with a majority being of reproductive age, creating environments that support breastfeeding physicians may help them meet their personal breastfeeding goals,5 improve their health and that of their own children,6, 7 and enhance their skills at providing breastfeeding care to their patients.5, 8 Breastfeeding physicians, as with all women who choose to breastfeed, need supportive environments to make breastfeeding a success. |
Summary of available surveillance data on hepatitis C virus infection from eight Arctic countries, 2012 to 2014
Gounder PP , Koch A , Provo G , Lovlie A , Ederth JL , Axelsson M , Archibald CP , Hanley B , Mullen A , Matheson M , Allison D , Trykker H , Hennessy TW , Kuusi M , Chulanov V , McMahon BJ . Euro Surveill 2018 23 (40) We summarised available hepatitis C virus (HCV) surveillance data for 2012-14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19-64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected. |
Tuberculosis in the circumpolar region, 2006-2012
Bourgeois AC , Zulz T , Bruce MG , Stenz F , Koch A , Parkinson A , Hennessy T , Cooper M , Newberry C , Randell E , Proulx JF , Hanley BE , Soini H , Arnesen TM , Mariandyshev A , Jonsson J , Soborg B , Wolfe J , Balancev G , De Neergaard RB , Archibald CP . Int J Tuberc Lung Dis 2018 22 (6) 641-648 Setting: The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska). Objective : To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations. Design: Descriptive analysis of all active TB cases reported from 2006 to 2012 for incidence rate (IR), age and sex distribution, sputum smear and diagnostic site characteristics, drug resistance and treatment completion rates. Results : The annual IR of TB disease ranged from a low of 4.3 per 100 000 population in Northern Sweden to a high of 199.5/100 000 in Nunavik, QC, Canada. For all jurisdictions, IR was higher for males than for females. Yukon had the highest proportion of new cases compared with retreatment cases (96.6%). Alaska reported the highest percentage of laboratory-confirmed cases (87.4%). Smear-positive pulmonary cases ranged from 25.8% to 65.2%. Multidrug-resistant cases ranged from 0% (Northern Canada) to 46.3% (Arkhangelsk). Treatment outcome data, available up to 2011, demonstrated >80% treatment completion for four of the 10 jurisdictions. Conclusion: TB remains a serious public health issue in the circumpolar regions. Surveillance data contribute toward a better understanding and improved control of TB in the north. |
A cynomolgus macaque model for Crimean-Congo haemorrhagic fever
Haddock E , Feldmann F , Hawman DW , Zivcec M , Hanley PW , Saturday G , Scott DP , Thomas T , Korva M , Avsic-Zupanc T , Safronetz D , Feldmann H . Nat Microbiol 2018 3 (5) 556-562 Crimean-Congo haemorrhagic fever (CCHF) is the most medically significant tick-borne disease, being widespread in the Middle East, Asia, Africa and parts of Europe (1) . Increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of CCHF as a public health threat. Ixodid ticks of the genus Hyalomma are the vector for CCHF virus (CCHFV), an arbovirus in the genus Orthonairovirus of the family Nairoviridae. CCHFV naturally infects numerous wild and domestic animals via tick bite without causing obvious disease(2,3). Severe disease occurs only in humans and transmission usually happens through tick bite or contact with infected animals or humans. The only CCHF disease model is a subset of immunocompromised mice(4-6). Here, we show that following CCHFV infection, cynomolgus macaques exhibited hallmark signs of human CCHF with remarkably similar viral dissemination, organ pathology and disease progression. Histopathology showed infection of hepatocytes, endothelial cells and monocytes and fatal outcome seemed associated with endothelial dysfunction manifesting in a clinical shock syndrome with coagulopathy. This non-human primate model will be an invaluable asset for CCHFV countermeasures development. |
Interpregnancy Interval and Adverse Pregnancy Outcomes: An Analysis of Successive Pregnancies
Ahrens KA , Thoma ME , Rossen LM . Obstet Gynecol 2017 130 (2) 464 Hanley et al1 present a compelling analysis of interpregnancy intervals and adverse pregnancy outcomes using a case-crossover design to analyze data from Canadian women with at least three deliveries between 2000 and 2015. Consistent with a previous analysis,2 the authors found that adverse associations between short interpregnancy interval and neonatal outcomes commonly reported in studies using unmatched analyses were erased (or even reversed) after conducting a case-crossover analysis. Although we agree with Hanley et al that time-invariant confounding is most likely reduced when using a within-woman study design such as case-crossover analysis, it may be at the expense of generalizability. | | As the study authors point out, unmatched designs use information from all women, whereas case-crossover analyses use information only from women with discordant exposures and outcomes.1,3 According to the article’s appendix tables, of the 38,178 women with at least three deliveries included in the unmatched analysis, 14% had discordant preterm birth outcomes (n = 5,195). Because 27% of women overall had discordant interpregnancy intervals (one in the reference group, one not in the reference group), approximately 3.8% (n = 1,457) of the total cohort presumably provided data for the case-crossover analysis on preterm birth. Although the authors note that their results may not generalize to other settings, further work on the generalizability of case-crossover analyses, which by design exclude individuals who have not experienced the outcome under study, to the broader target population would be welcome.4 |
Exploring manganese fractionation using a sequential extraction method to evaluate welders' gas metal arc welding exposures during heavy equipment manufacturing
Hanley KW , Andrews R , Bertke S , Ashley K . Ann Work Expo Health 2017 61 (1) 123-134 The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume at three factories where heavy equipment was manufactured. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. One hundred nine worker-days were monitored for either total or respirable Mn during gas metal arc welding. The samples were analyzed using an experimental method to separate different Mn fractions based on selective chemical solubility. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged 0.38-26 for soluble Mn in a mild ammonium acetate solution; 3.2-170 for Mn0,2+ in acetic acid; 3.1-290 for Mn3+,4+ in hydroxylamine-hydrochloride; and non-detectable (ND)-130 microg m-3 for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all the total particulate Mn TWA fractions yielded results that ranged from 6.9 to 610 microg m-3. The range of respirable size Mn TWA concentrations were 0.33-21 for soluble Mn; 15-140 for Mn0,2+; 14-170 for Mn3+,4+; 5.3-230 for insoluble Mn; and 36-530 microg m-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn (sum) were 53 (GSD = 2.5), 150 (GSD = 1.7), and 120 (GSD = 1.8) microg m-3 for the three separate factories. Although all of the workers' exposures were measured below the OSHA regulatory permissible exposure limit and NIOSH recommended exposure limit for Mn, 70 welders' exposures exceeded the ACGIH Threshold Limit Values(R) for total Mn (100 microg m-3) and 29 exceeded the recently adopted respirable Mn TLV (20 microg m-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding parts that impede air circulation. |
An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA
Tyndall JA , Gerona R , De Portu G , Trecki J , Elie MC , Lucas J , Slish J , Rand K , Bazydlo L , Holder M , Ryan MF , Myers P , Iovine N , Plourde M , Weeks E , Hanley JR , Endres G , Germaine DS , Dobrowolski PJ , Schwartz M . Clin Toxicol (Phila) 2015 53 (10) 1-7 BACKGROUND: Synthetic cannabinoid containing products are a public health threat as reflected by a number of outbreaks of serious adverse health effects over the past 4 years. The designer drug epidemic is characterized by the rapid turnover of synthetic cannabinoid compounds on the market which creates a challenge in identifying the particular etiology of an outbreak, confirming exposure in cases, and providing current information to law enforcement. RESULTS: Between 28 May 2014 and 8 June 2014, 35 patients were evaluated and treated at the University of Florida Health Medical Center in Gainesville following reported exposure to a synthetic cannabinoid containing product obtained from a common source. Patients demonstrated acute delirium (24) and seizures (14), and five required ventilator support and ICU-level care; none died. The presence of N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carb oxamide (AB-CHMINACA), or one of its predicted metabolites was confirmed in 15 of 21 cases. A rapid public health response and aggressive public messaging prevented further morbidity, identified the source, and led to law enforcement seizure of the implicated product. DISCUSSION: The significance of this outbreak lies as much in the rapid occurrence of unpredictable, life-threatening adverse health effects from a newly identified synthetic cannabinoid compound as it does in the multidisciplinary investigation and novel partnership between local public health, the laboratory, and the chemical industry, resulting in termination of the outbreak. CONCLUSION: A coordinated response and collaboration between law enforcement, the local public health, emergency medical services and Health Center staff, were all key interventions in preventing a more substantial public health outbreak resulting from use of a novel synthetic cannabinoid compound. Real time collaborations between toxicology laboratories, suppliers of analytical standards and the public health system may be useful in the face of future novel chemical exposures. |
Manganese speciation of laboratory-generated welding fumes
Andrews RN , Keane M , Hanley KW , Feng HA , Ashley K . Anal Methods 2015 7 6403-6410 The objective of this laboratory study was to identify and measure manganese (Mn) fractions in chamber-generated welding fumes (WF) and to evaluate and compare the results from a sequential extraction procedure for Mn fractions with that of an acid digestion procedure for measurement of total, elemental Mn. To prepare Mn-containing particulate matter from representative welding processes, a welding system was operated in short circuit gas metal arc welding (GMAW) mode using both stainless steel (SS) and mild carbon steel (MCS) and also with flux cored arc welding (FCAW) and shielded metal arc welding (SMAW) using MCS. Generated WF samples were collected onto polycarbonate filters before homogenization, weighing and storage in scintillation vials. The extraction procedure consisted of four sequential steps to measure various Mn fractions based upon selective solubility: (1) soluble Mn dissolved in 0.01 M ammonium acetate; (2) Mn(0,ii) dissolved in 25% (v/v) acetic acid; (3) Mn(iii,iv) dissolved in 0.5% (w/v) hydroxylamine hydrochloride in 25% (v/v) acetic acid; and (4) insoluble Mn extracted with concentrated hydrochloric and nitric acids. After sample treatment, the four fractions were analyzed for Mn by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). WF from GMAW and FCAW showed similar distributions of Mn species, with the largest concentrations of Mn detected in the Mn(0,ii) and insoluble Mn fractions. On the other hand, the majority of the Mn content of SMAW fume was detected as Mn(iii,iv). Although the concentration of Mn measured from summation of the four sequential steps was statistically significantly different from that measured from the hot block dissolution method for total Mn, the difference is small enough to be of no practical importance for industrial hygiene air samples, and either method may be used for Mn measurement. The sequential extraction method provides valuable information about the oxidation state of Mn in samples and allows for comparison to results from previous work and from total Mn dissolution methods. |
Manganese fractionation using a sequential extraction method to evaluate welders' shielded metal arc welding exposures during construction projects in oil refineries
Hanley KW , Andrews R , Bertke S , Ashley K . J Occup Environ Hyg 2015 12 (11) 0 The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume of construction workers rebuilding tanks, piping, and process equipment at two oil refineries. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Seventy-two worker-days were monitored for either total or respirable Mn during stick welding and associated activities both within and outside of confined spaces. The samples were analyzed using an experimental method to separate different Mn fractions by valence states based on selective chemical solubility. The full-shift total particulate Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.013 - 29 for soluble Mn in a mild ammonium acetate solution; from 0.26 - 250 for Mn0,2+ in acetic acid; from non-detectable (ND) - 350 for Mn3+,4+ in hydroxylamine-hydrochloride; and from ND - 39 micrograms per cubic meter (microg/m3) for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all Mn fractions in total particulate TWA ranged from 0.52 to 470 microg/m3. The range of respirable particulate Mn TWA concentrations were from 0.20 - 28 for soluble Mn; from 1.4 - 270 for Mn0,2+; from 0.49 - 150 for Mn3+,4+; from ND - 100 for insoluble Mn; and from 2.0 - 490 microg/m3 for Mn (sum of fractions). For all jobs combined, total particulate TWA GM concentrations of the Mn(sum) were 99 (GSD=3.35) and 8.7 (GSD=3.54) microg/m3 for workers inside and outside of confined spaces; respirable Mn also showed much higher levels for welders within confined spaces. Regardless of particle size and confined space work status, Mn0,2+ fraction was the most abundant followed by Mn3+,4+ fraction, typically >50% and 30-40% of Mn(sum), respectively. Eighteen welders' exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 microg/m3) and 25 exceeded the recently adopted respirable Mn TLV (20 microg/m3). This study shows that a welding fume exposure control and management program is warranted, especially for welding jobs in confined spaces. |
Depot-medroxyprogesterone acetate does not reduce the prophylactic efficacy of emtricitabine and tenofovir disoproxil fumarate in macaques
Radzio J , Hanley K , Mitchell J , Ellis S , Deyounks F , Jenkins L , Heneine W , Garcia-Lerma JG . J Acquir Immune Defic Syndr 2014 67 (4) 365-9 Concerns that the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition in women led to questions on whether DMPA could reduce efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model to investigate the impact of prolonged DMPA on PrEP with FTC/TDF. Twelve pigtail macaques treated with DMPA were exposed vaginally to SHIV once a week for up to 5 months and received either placebo (n=6) or FTC/TDF (n=6). All control macaques were infected while the PrEP-treated animals remained protected (p=0.0007). This model suggests that women using DMPA will fully benefit from PrEP. |
Physiologic doses of depot-medroxyprogesterone acetate do not increase acute plasma simian HIV viremia or mucosal virus shedding in pigtail macaques
Radzio J , Hanley K , Mitchell J , Ellis S , Deyounks F , Jenkins LT , Hanson D , Heneine W , Garcia-Lerma JG . AIDS 2014 28 (10) 1431-9 OBJECTIVE: Epidemiologic studies remain inconclusive on whether the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) increases mucosal HIV shedding and transmissibility. Nonhuman primate models may help to determine the effects of DMPA on acute HIV replication. DESIGN: We defined a physiologic dose of DMPA in macaques and assessed the impact of DMPA on acute simian HIV (SHIV) replication. METHODS: Pigtail macaques received 1-30 mg of DMPA intramuscularly followed by measurements of progesterone and medroxyprogesterone acetate (MPA). Vaginal epithelial thickness, number of cell layers and density of intraepithelial CD3 cells were measured. The effect of DMPA on SHIV viremia and genital virus shedding was investigated in six pigtail macaques infected during monthly treatment cycles with 3 mg DMPA. Six DMPA-untreated macaques were controls. RESULTS: Plasma MPA concentrations directly correlated with changes in epithelial thickness (correlation = 0.84; P < 0.001) and density of intraepithelial CD3 cells (correlation = 0.41; P = 0.02). A 3 mg DMPA dose recapitulated plasma MPA concentrations and changes in vaginal epithelial thickness seen in women. DMPA-treated and untreated macaques showed similar peak plasma viremia and RNA area under the curve0-12wk values (P = 0.94), although treated macaques had higher odds of having virus being detected in plasma (odds ratio 6.6, P = 0.02). Rectal and vaginal virus shedding was similar between treated and untreated macaques (P = 0.72 and P = 0.53, respectively). CONCLUSION: In this pigtail macaque model of DMPA and vaginal SHIV infection, we found little or no effect of DMPA on plasma viremia and mucosal virus shedding during acute infection. These results do not support a role of DMPA in increasing mucosal virus shedding. |
Coronary artery disease and cancer mortality in a cohort of workers exposed to vinyl chloride, carbon disulfide, rotating shift work, and o-toluidine at a chemical manufacturing plant
Carreon T , Hein MJ , Hanley KW , Viet SM , Ruder AM . Am J Ind Med 2014 57 (4) 398-411 BACKGROUND: We updated through 2007 the mortality experience of 1,874 workers employed at a New York State chemical manufacturing plant between 1946 and 2006. METHODS: Reassessed exposures to vinyl chloride, carbon disulfide, and shift work and categories of o-toluidine exposure were based on year, department and job title. Standardized mortality ratios (SMR) compared mortality to that of the US population. Internal comparisons used directly standardized rate ratios. RESULTS: Hepatobiliary cancer mortality was elevated among workers ever exposed to vinyl chloride (SMR = 3.80, 95% confidence interval 1.89-6.80); directly standardized rates increased with increasing vinyl chloride exposure duration. No increase in non-Hodgkin lymphoma mortality was observed with vinyl chloride and shift work exposures. Internal comparisons showed increased coronary artery disease mortality among long-term workers exposed to carbon disulfide and shift work for 4 years or more. CONCLUSIONS: Excess coronary artery disease mortality confirms earlier results; further investigation is needed to understand risk factors. |
Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant
Carreon T , Hein MJ , Hanley KW , Viet SM , Ruder AM . Occup Environ Med 2013 71 (3) 175-82 BACKGROUND: An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. METHODS: Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. RESULTS: Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. CONCLUSIONS: Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits. |
Exposure to o-toluidine, aniline, and nitrobenzene in a rubber chemical manufacturing plant: a retrospective exposure assessment update
Hanley KW , Viet SM , Hein MJ , Carreon T , Ruder AM . J Occup Environ Hyg 2012 9 (8) 478-90 The National Institute for Occupational Safety and Health previously conducted a retrospective cancer incidence and mortality study of workers employed at a rubber chemical manufacturing plant. Compared with New York State incidence, the bladder cancer risk was 6.5 times higher for workers considered to have definite exposure to ortho-toluidine and aniline, and 4 times higher for workers with possible exposure. Exposure characterization in the original study utilized a surrogate measure based only on departments in which each worker was ever employed. As part of an update of that study, some departments in the three original exposure groups were reclassified based on a follow-up site visit; interviews with employees, management, and union representatives; and review of records including exposure data. An additional evaluation of department-job combinations, rather than only departments, was used to stratify exposure into four categories. An approximate rank of "relative" exposure level for each department-job-year combination was also assigned using a ranking scale of 0 to 10. The ranks were supported by quantitative exposure levels and by professional judgment. The numerical ranking scale was applied to each worker by multiplying the exposure rank by duration for each job held based on comprehensive individual work histories. The cumulative rank scores for this cohort ranged from 0 to 300 unit-years. The medians of the cumulative rank scores for the exposure categories showed very good agreement with increasing exposure classifications (e.g., 0.72, 4.6, 11, 14 unit-years for the four exposure categories). Workers' breathing zone air sampling data collected at this plant from 1976-2004 were well below published occupational exposure limits for these chemicals, but additional cases of bladder cancer have been reported. The exposure assessment revisions and rank estimates will be used to analyze the updated bladder cancer incidence data. |
Comparison and evaluation of urinary biomarkers for occupational exposure to spray adhesives containing 1- bromopropane
Mathias PI , Cheever KL , Hanley KW , Marlow KL , Johnson BC , B'Hymer C . Toxicol Mech Methods 2012 22 (7) 526-32 Three metabolites of 1-bromopropane (1-BP) were measured in urine samples collected from 30 workers exposed to 1-BP at two facilities making furniture seat cushions and evaluated for use as biomarkers of exposure. The mercapturic acid metabolite,N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), 3-bromopropionic acid (3-BPA), and bromide ion levels (Br(-)) were quantitated for this evaluation. The high exposure group consisted of 13 workers employed as adhesive sprayers who assembled foam cushions using 1-BP containing spray adhesives and the low exposure group consisted of 17 non-sprayers, who worked in various jobs without spraying adhesives. All workers' urine voids were collected over the same 48 hour period at work, and at home before bedtime, and upon awakening. Urinary AcPrCys and Br(-)levels were elevated in the sprayers compared to that ofnon-sprayers. Following HPLC-MS/MS analysis of mercapturic acid metabolite levels, 50 urine samples having the highest levels of AcPrCys were analyzed for 3-BPA. No 3-BPA was detected in any of the samples. The data collected from this study demonstrate that ACPrCys and Br(-) are effective biomarkers of 1-BP exposure, but 3-BPA is not. |
Isolation, morphologic, serologic and molecular identification of Acanthamoeba T4 genotype from the liver of a Temminck's tragopan (Tragopan temminckii)
Visvesvara GS , Shoff ME , Sriram R , Booton GC , Crary M , Fuerst PA , Hanley CS , Garner MM . Vet Parasitol 2010 170 197-200 Members of the genus Acanthamoeba are usually free-living amoebae that are found in a variety of ecological niches including soil, fresh and brackish water, dust in the air, heating, ventilating, and air conditioning filters, swimming pools and hot tubs. Occasionally they are also known to cause central nervous system infections in humans and animals. We isolated into culture an amoeba from the liver of a Temminck's tragopan (horned pheasant) (Tragopan temminckii) that died of amoebic infection. We identified the infecting amoeba as Acanthamoeba sp. based on culture characteristics, cyst morphology and immunofluorescence assays. Additionally, we identified the amoeba as Acanthamoeba, genotype T4, by sequencing a diagnostic region of the nuclear small subunit ribosomal RNA gene. |
Bromide and N-acetyl-S-(n-propyl)-L: -cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing or adhesive manufacturing
Hanley KW , Petersen MR , Cheever KL , Luo L . Int Arch Occup Environ Health 2010 83 (5) 571-84 OBJECTIVES: 1-Bromopropane (1-BP) is an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, and cleaning solvents. There is concern that 1-BP may be a reproductive and neurological toxicant. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. The main objectives were to evaluate urinary bromide [Br((-))] and N-acetyl-S-(n-propyl)-L: -cysteine (AcPrCys) for assessing 1-BP exposure in workers with low exposure. METHODS: Workers' 1-BP exposures were measured in their breathing zones with gas chromatography-flame ionization detection via NIOSH 1025. Urine specimens were obtained over a 48-h period at five facilities using vapor degreasers and one adhesive manufacturer. All of the workers' urine was collected into composite samples and analyzed separately representing daily time intervals: at work, after work but before bedtime, and upon awakening. Urinary metabolites were analyzed using intra-coupled plasma-mass spectroscopy for Br((-)), and high-performance liquid chromatography and electro-spray ionization mass spectroscopy for AcPrCys. RESULTS: Time-weighted average (TWA) geometric mean (GM) breathing zone concentrations of 1-BP at vapor degreasing facilities were 2.6 and 0.31 ppm, respectively, for workers near degreasers and those remote from degreasers. Urine metabolites showed the same trend as TWA exposures: higher levels were observed for workers near degreasers (48-h GM Br((-)) = 8.9 vs. 3.7; 48-h GM AcPrCys = 1.3 vs. 0.12, respectively). Associations of Br((-)) and AcPrCys concentrations with 1-BP TWA were statistically significant near degreasers (p < 0.01). CONCLUSIONS: This study shows that urinary Br((-)) and AcPrCys are useful biomarkers of workers' 1-BP exposures using analyses sensitive enough to measure low exposure jobs. |
Increased bladder cancer risk among workers exposed to o-toluidine and aniline: a reanalysis
Carreon T , Hein MJ , Viet SM , Hanley KW , Ruder AM , Ward EM . Occup Environ Med 2009 67 (5) 348-50 INTRODUCTION: In 1991, the U.S. National Institute for Occupational Safety and Health (NIOSH) reported an increased bladder cancer risk in a cohort of 1749 workers potentially exposed to o-toluidine and aniline at a chemical manufacturing plant. Additional information showed that workers in certain departments had been misclassified regarding o-toluidine exposure; therefore, we conducted a reanalysis of the data using updated exposure categories. METHODS: We updated exposure categories based on information ascertained during a plant walkthrough, documents on file at the plant, interviews with current and former employees, and answers provided by company and union officials on specific questions. Bladder cancer incidence was determined through 31 December 1988 and mortality through 31 December 1994. RESULTS: Thirteen cases of bladder cancer were observed, versus 3.57 expected (New York State rates excluding New York City) [standardized incidence ratio (SIR) 3.64, 95% confidence interval (CI) 1.94-6.23]. Among workers classified as definitely exposed, increasing risks were observed for longer duration of employment [for ≥10 years, standardized rate ratio (SRR) 6.07, 95% CI 0.77-48.17] and time since first employment in the exposed departments (for ≥20 years, SRR 3.39, 95% CI 0.40-29.03). One bladder cancer death was observed among those definitely exposed. CONCLUSION: These findings are comparable to the results reported earlier by NIOSH, and confirm that workers in this plant have an increased risk of bladder cancer. |
N-acetyl-S-(n-propyl)-l-cysteine in urine from workers exposed to 1-bromopropane in foam cushion spray adhesives
Hanley KW , Petersen MR , Cheever KL , Luo L . Ann Occup Hyg 2009 53 (7) 759-69 1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, metal, precision, and electronics cleaning solvents. Mechanisms of toxicity of 1-BP are not fully understood, but it may be a neurological and reproductive toxicant. Sparse exposure information prompted this study using 1-BP air sampling and urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. Research objectives were to evaluate the utility of urinary N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing exposure to 1-BP and compare it to urinary bromide [Br((-))] previously reported for these workers. Forty-eight-hour urine specimens were obtained from 30 workers at two factories where 1-BP spray adhesives were used to construct polyurethane foam seat cushions. Urine specimens were also obtained from 21 unexposed control subjects. All the workers' urine was collected into composite samples representing three time intervals: at work, after work but before bedtime, and upon awakening. Time-weighted average (TWA) geometric mean breathing zone concentrations were 92.4 and 10.5 p.p.m. for spraying and non-spraying jobs, respectively. Urinary AcPrCys showed the same trend as TWA exposures to 1-BP: higher levels were observed for sprayers. Associations of AcPrCys concentrations, adjusted for creatinine, with 1-BP TWA exposure were statistically significant for both sprayers (P < 0.05) and non-sprayers (P < 0.01). Spearman correlation coefficients for AcPrCys and Br((-)) analyses determined from the same urine specimens were highly correlated (P < 0.0001). This study confirms that urinary AcPrCys is an important 1-BP metabolite and an effective biomarker for highly exposed foam cushion workers. |
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