BACKGROUND: Antibiotic resistance is a global health concern. Humans can acquire antibiotic resistance through human-to-human transmission, from the environment, via the food chain, and through the contact with animals. The National Action Plan on antimicrobial resistance 2020-2024 highlights the prudent use of antibiotics in veterinary activities as the key element in keeping antibiotics effective. We determined the factors associated with misuse of antibiotics among animal health professionals in Rwanda. METHODS: This was a cross-sectional study that enrolled animal health field professionals from five districts, where stratified random sampling was used to select one district by each province of Rwanda. Structured questions were used during face-to-face interviews. The misuse of antibiotics was defined as the use of antibiotics for reasons other than treatment, the non-completion of required courses, or the use of a high dose (i.e., an overdose) of antibiotics. We collected socio-demographic data of respondents, as well as elementary knowledge and perceptions on veterinary antibiotics and antibiotic resistance. A backward stepwise logistic regression model was used to identify the factors that were predictive of the inappropriate use of antibiotics. RESULTS: There were 256 respondents to the survey. Of those, 198 were male and 58 were female. Almost three quarters of respondents (n = 174/256; 68%) reported the misuse of antibiotics at least once in the previous 12 months. The final logistic regression analysis identified the following factors to be predictive of antibiotics misuse: aged ≤ 24 years (aOR 0.92; 95% CI [0.88, 0.96]; p < 0.001); low trust in veterinary antibiotics available in the local market (aOR 8.45; 95% CI [4.18, 17.07]; p < 0.01), insufficient knowledge about basic understanding of antibiotics and antibiotic resistance (aOR 2.78; 95% CI [1.38, 5.58], p < 0.01) and not acquiring any continuing education (aOR 1.97; 95% CI [1.02, 4.19]; p = 0.04). CONCLUSIONS: This study identified inadequate perceptions of proper antibiotic use among animal health professionals. There is a need for continuous education on appropriate antibiotic use among animal health professionals to lessen the negative impact of antibiotic resistance on public health security.

Nebulizers are commonly employed for inhaled drug delivery. As they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The coronavirus disease 2019 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could negatively impact outcomes, especially for patients who may not derive full treatment benefit from hand-held inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that may also be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this Expert Guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting, and one for the home environment. Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient-care situations and to evaluate the effectiveness of mitigation strategies.

Coffee production workers are exposed to complex mixtures of gases, dust, and vapors, including the known respiratory toxins, diacetyl, and 2,3-pentanedione, which occur naturally during coffee roasting and are also present in flavorings used to flavor coffee. This study evaluated the associations of these two -diketones with lung function measures in coffee production workers. Workers completed questionnaires, and their lung function was assessed by spirometry and impulse oscillometry (IOS). Personal exposures to diacetyl, 2,3-pentanedione, and their sum (Sum(DA+PD)) were assigned to participants, and metrics of the highest 95th percentile (P95), cumulative, and average exposure were calculated. Linear and logistic regression models for continuous and binary/polytomous outcomes, respectively, were used to explore exposure-response relationships adjusting for age, body mass index, tenure, height, sex, smoking status, race, or allergic status. Decrements in percent predicted forced expiratory volume in 1 second (ppFEV(1)) and forced vital capacity (ppFVC) were associated with the highest-P95 exposures to 2,3-pentanedione and Sum(DA+PD). Among flavoring workers, larger decrements in ppFEV(1) and ppFVC were associated with highest-P95 exposures to diacetyl, 2,3-pentanedione, and Sum(DA+PD). Abnormal FEV(1), FVC, and restrictive spirometric patterns were associated with the highest-P95, cumulative, and average exposures for all -diketone metrics; some of these associations were also present among flavoring and non-flavoring workers. The combined category of small and peripheral airways plus small and large airways abnormalities on IOS had elevated odds for highest-P95 exposure to -diketones. These results may be affected by the small sample size, few cases of abnormal spirometry, and the healthy worker effect. Associations between lung function abnormalities and exposure to -diketones suggest it may be prudent to consider exposure controls in both flavoring and non-flavoring settings.

INTRODUCTION: Ulcerative STIs, including syphilis, increase the risk for HIV acquisition and transmission due to the presence of ulcers/chancres that serve as a point-of-entry and exit for HIV. In Zimbabwe, diagnosis of syphilis often occurs in pregnant women who seek ANC services where syphilis testing is offered, and among men and women who seek health care for STIs. Zimbabwe's national syphilis estimates are based on these diagnosed cases, with little information available about the prevalence of untreated syphilis among the general population. This analysis uses data from ZIMPHIA (2015-2016) to describe factors associated with active syphilis among men and women ages 15 years and older. METHODS: ZIMPHIA collected blood specimens for HIV and syphilis testing from 22,501 consenting individuals (ages 15 years and older). Household HIV testing used the national HIV rapid-testing algorithm with HIV-positive results confirmed at satellite laboratories using Geenius HIV-1/2 rapid test (Bio-rad, Hercules, California, USA). Point-of-care non-Treponemal and Treponemal syphilis testing was performed using Chembio's Dual-Path Platform Syphilis Screen & Confirm Assay. Factors associated with active syphilis were explored using multiple variable, weighted logistic regression and were stratified by gender. RESULTS: The likelihood of active syphilis in HIV-positive females was 3.7 times greater in HIV-positive females than HIV-negative females (aOR: 3.7, 95% CI 2.3-5.9). Among males odds of having active syphilis was 5 times higher among those that engaged in transactional sex than those who did not have sex or transactional sex (aOR: 5.3, 95% CI 1.9-14.7), and 6 times higher if HIV positive versus negative (aOR: 5.9, 95% CI 3.0-12.0). Urban residence, province, education (highest attended), marital status, number of sex partners, consistency of condom use, pregnancy status (females), and circumcision status (males) were not significant in the adjusted model for either females or males. CONCULSION: HIV status was found to be the only factor associated with active syphilis in both females and males. Given the persistent link between HIV and active syphilis, it is prudent to link individuals' diagnoses and treatments, as recommended by the WHO. Enhanced integration of STI and HIV services in health delivery points such as ANC, reproductive services, or male circumcision clinics, combined with consistent, targeted outreach to high-risk populations and their partners, may assist the MOHCC to eliminate active syphilis in Zimbabwe.

The popularity of electronic cigarettes (electronic nicotine delivery systems or ENDS) has grown rapidly over the past decade. With the continued evolution of ENDS, and the arrival of newer replaceable pod devices on the market, it is prudent to examine their emissions to help determine potential health risks to the user. Metal containing particles were examined in aerosol from several pod-based devices from three manufacturers that offer flavored liquids in their respective products. Previous ENDS metal emissions studies focused on the total toxic metal concentrations in aerosols and have suggested that the principal sources are oxidized internal metal components that are in contact with the liquid. Most metal oxides have limited solubility and it is likely that some metal content in ENDS aerosol may present as particles rather than dissolved forms. Examining the composition and number of particles in the ENDS aerosols is important because inhaled metal oxide particles cause pulmonary inflammation. Chronic inhalation of ENDS aerosol may lead to inflammatory cell activation in the lungs. Therefore, this study was designed to measure metal oxide particle concentrations and sizes in ENDS aerosols from select pod-based systems. Aerosol samples were generated with pod liquids (tobacco, mint or menthol) from devices produced by three manufacturers using CORESTA Recommended Method 81 parameters with a high purity fluoropolymer aerosol trap. Particle sizes for chromium, iron, nickel, copper, zinc, tin, and lead oxides were measured in triplicate using single particle inductively coupled plasma-mass spectrometry and dynamic light scattering. A novel aspect of these measurements included using dual element particle analysis to infer particle source component material. Particle concentrations in aerosols from the devices were variable between devices and from pod to pod, ranging from no detectable chromium and zinc containing particles in aerosol from some pods to 222,000 lead containing particles per 10 puffs from individual pods.

Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.

OBJECTIVE: To report the incidence of prion disease in the United States. METHODS: Prion disease decedents were retrospectively identified from the US national multiple cause-of-death data for 2003-2015 and matched with decedents in the National Prion Disease Pathology Surveillance Center (NPDPSC) database through comparison of demographic variables. NPDPSC decedents with neuropathologic or genetic test results positive for prion disease for whom no match was found in the multiple cause-of-death data were added as cases for incidence calculations; those with cause-of-death data indicating prion disease but with negative neuropathology results were removed. Age-specific and age-adjusted average annual incidence rates were then calculated. RESULTS: A total of 5,212 decedents were identified as having prion disease, for an age-adjusted average annual incidence of 1.2 cases per million population (range 1.0 per million [2004 and 2006] to 1.4 per million [2013]). The median age at death was 67 years. Ten decedents were <30 years of age (average annual incidence of 6.2 per billion); only 2 of these very young cases were sporadic forms of prion disease. Average annual incidence among those >/=65 years of age was 5.9 per million. CONCLUSIONS: Prion disease incidence can be estimated by augmenting mortality data with the results of neuropathologic and genetic testing. Cases <30 years of age were extremely rare, and most could be attributed to exogenous factors or the presence of a genetic mutation. Continued vigilance for prion diseases in all age groups remains prudent.

BACKGROUND: Recent studies of influenza vaccine effectiveness (VE) observed lower effectiveness with increasing time since vaccination, raising the question of optimal vaccination timing. We sought to evaluate the estimated number of influenza-associated hospitalizations among older adults due to potential changes in vaccination timing. METHODS: Using empirical data and a health state transition model, we estimated change in influenza-associated hospitalizations predicted to occur among the U.S. population aged >/=65 years if vaccination were delayed until October 1. We assumed the vaccination timing, coverage, and effectiveness observed in 2012-13 as a prototypical influenza season, ~7% monthly waning of VE, and that between 0% and 50% of individuals who usually get vaccinated earlier than October failed to get vaccinated. We also assessed change in influenza-associated hospitalizations if vaccination uptake shifted substantially toward August and September. RESULTS: In a typical season, delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. The consequences of delayed vaccination depended heavily on influenza season timing, rate of waning, and overall VE. A shift toward vaccination in August and September led to, on average, an increase in influenza-associated hospitalizations, but this result was also sensitive to influenza season timing. CONCLUSIONS: Consequences of delayed vaccination varied widely. Uncertainties about vaccine waning and effects of a delay on vaccine coverage suggest it is premature to change current vaccine recommendations, although it may be prudent to prevent a substantial shift toward early vaccination.

Understanding healthcare seeking and utilization of members of discordant couples can help in implementing effective HIV treatment, care, and support. We conducted a qualitative study comprised of in-depth interviews (n = 26) and ten focus group discussions (n = 73) with community members including opinion leaders, healthcare workers, and members of discordant couples. A portion of the latter group had been participants in the HIV Prevention Trials Network (HPTN) 052 study. Themes that emerged from the data were pragmatism and the realities of hospital care, quest for a cure through traditional medicine, and religious dogma. Medical pluralism is practiced by members of discordant couples seeking HIV care through intersections of hospital facility services and traditional and religious therapeutic options. It would be prudent for healthcare policy makers and conventional medical providers to recognize the importance of traditional medicine and religion in the lives of members of HIV discordant couples and make efforts to integrate the positive concepts of both into the couples' overall health plan.

Fused deposition modeling (FDM() ) 3-dimensional printing uses polymer filament to build objects. Some polymer filaments are formulated with additives, though it is unknown if they are released during printing. Three commercially-available filaments that contained carbon nanotubes (CNTs) were printed with a desktop FDM() 3-D printer in a chamber while monitoring total particle number concentration and size distribution. Airborne particles were collected on filters and analyzed using electron microscopy. Carbonyl compounds were identified by mass spectrometry. The elemental carbon content of the bulk CNT-containing filaments was 1.5 to 5.2 wt%. CNT-containing filaments released up to 10(10) ultrafine (d <100 nm) particles/g printed and 10(6) to 10(8) respirable (d ~0.5 to 2 mum) particles/g printed. From microscopy, 1% of the emitted respirable polymer particles contained visible CNTs. Carbonyl emissions were observed above the limit of detection (LOD) but were below the limit of quantitation (LOQ). Modeling indicated that for all filaments, the average proportional lung deposition of CNT-containing polymer particles was 6.5%, 5.7%, and 7.2% for the head airways, tracheobronchiolar, and pulmonary regions, respectively. If CNT-containing polymer particles are hazardous, it would be prudent to control emissions during use of these filaments. This article is protected by copyright. All rights reserved.

BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95.4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13.2 (95% credible interval [CrI] 11.2-15.6) per 1000 livebirths and of viral infections was 10.1 (9.4-11.6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5.4, 95% CrI 4.8-6.3 episodes per 1000 livebirths), followed by Ureaplasma spp (2.4, 1.6-3.2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation.

Erionite is a naturally occurring fibrous mineral found in many parts of the world, including the western United States. Inhalational exposure to erionite fibers in some localities is associated with health effects similar to those caused by asbestos exposure, including malignant mesothelioma. Therefore, there is concern regarding occupational exposures in the western United States. Currently there are no standard sampling and analytical methods for airborne erionite fibers, as well as no established occupational exposure limits. Due to the potential adverse health effects, characterizing and minimizing exposures is prudent. Crystalline silica also occurs naturally in areas where erionite is found, principally as the mineral quartz. Work activities involving rocks containing quartz and soils derived from those rocks can lead to exposure to respirable crystalline silica (RCS). The typically dry and dusty environment of the western United States can increase the likelihood of exposures to aerosolized rocks and soils, but inhalation exposure is also possible in more humid conditions. In this case study, we describe several outdoor occupational environments with potential exposures to erionite and RCS. We describe our method for evaluating those exposures and demonstrate: (1) the occurrence of occupational exposures to airborne erionite and RCS, (2) that the chemical make-up of the erionite mineral can be determined, and (3) that effective dust control practices are needed to reduce employee exposures to these minerals.

Control banding (CB) has been widely recommended for the selection of exposure controls for engineered nanomaterials (ENMs) in the absence of ENM-specific occupational exposure limits (OELs). Several ENM-specific CB strategies have been developed but have not been systematically evaluated. In this article, we identify the data inputs and compare the guidance provided by eight CB tools, evaluated on six ENMs, and assuming a constant handling/use scenario. The ENMs evaluated include nanoscale silica, titanium dioxide, silver, carbon nanotubes, graphene, and cellulose. Several of the tools recommended the highest level of exposure control for each of the ENMs in the evaluation, which was driven largely by the hazard banding. Dustiness was a factor in determining the exposure band in many tools, although most tools did not provide explicit guidance on how to classify the dustiness (high, medium, low), and published data are limited on this topic. The CB tools that recommended more diverse control options based on ENM hazard and dustiness data appear to be better equipped to utilize the available information, although further validation is needed by comparison to exposure measurements and OELs for a variety of ENMs. In all CB tools, local exhaust ventilation was recommended at a minimum to control exposures to ENMs in the workplace. Generally, the same or more stringent control levels were recommended by these tools compared with the OELs proposed for these ENMs, suggesting that these CB tools would generally provide prudent exposure control guidance, including when data are limited.

Beginning in 2004, chikungunya virus (CHIKV) went from an endemic pathogen limited to Africa and Asia that caused periodic outbreaks to a global pathogen. Given that outbreaks caused by CHIKV have continued and expanded, serious consideration must be given to identifying potential options for vaccines and therapeutics. Currently, there are no licensed products in this realm, and control relies completely on the use of personal protective measures and integrated vector control, which are only minimally effective. Therefore, it is prudent to urgently examine further possibilities for control. Vaccines have been shown to be highly effective against vector-borne diseases. However, as CHIKV is known to rapidly spread and generate high attack rates, therapeutics would also be highly valuable. Several candidates are currently being developed; this review describes the multiple options under consideration for future development and assesses their relative advantages and disadvantages.

Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) assessed antiviral susceptibility of 14,330 influenza A and B viruses collected by WHO-recognized National Influenza Centres (NICs) between May 2015 and May 2016. Neuraminidase (NA) inhibition assay was used to determine 50% inhibitory concentration (IC50) data for NA inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Furthermore, NA sequences from 13,484 influenza viruses were retrieved from public sequence databases and screened for amino acid substitutions (AAS) associated with reduced inhibition (RI) or highly reduced inhibition (HRI) by NAIs. Of the viruses tested by WHO CCs 93% were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.8% (n = 113) exhibited either RI or HRI by at least one of four NAIs. As in previous seasons, the most common NA AAS was H275Y in A(H1N1)pdm09 viruses, which confers HRI by oseltamivir and peramivir. Two A(H1N1)pdm09 viruses carried a rare NA AAS, S247R, shown in this study to confer RI/HRI by the four NAIs. The overall frequency of A(H1N1)pdm09 viruses containing NA AAS associated with RI/HRI was approximately 1.8% (125/6915), which is slightly higher than in the previous 2014-15 season (0.5%). Three B/Victoria-lineage viruses contained a new AAS, NA H134N, which conferred HRI by zanamivir and laninamivir, and borderline HRI by peramivir. A single B/Victoria-lineage virus harboured NA G104E, which was associated with HRI by all four NAIs. The overall frequency of RI/HRI phenotype among type B viruses was approximately 0.6% (43/7677), which is lower than that in the previous season. Overall, the vast majority (>99%) of the viruses tested by WHO CCs were susceptible to all four NAIs, showing normal inhibition (NI). Hence, NAIs remain the recommended antivirals for treatment of influenza virus infections. Nevertheless, our data indicate that it is prudent to continue drug susceptibility monitoring using both NAI assay and sequence analysis.

Responses from N=60,598 interviews from the 2010 Behavioral Risk Factor Surveillance System (the 10 states and the District of Columbia that included the optional Adverse Childhood Experience (ACE) module) were used to test whether associations between childhood adversity and adult mental health and alcohol behaviors vary by race/ethnicity and sex. ACE items were categorized into two types - household challenges and child abuse. Outcomes were current depression, diagnosed depression, heavy drinking and binge drinking. Logistic regression models found ACEs significantly associated with depression and excessive alcohol use, but sex did not moderate any relationships. Race/ethnicity moderated the relationship between ACEs and heavy drinking. In stratified analyses, compared to those not exposed to ACEs, non-Hispanic blacks who experienced either type of ACE were about 3 times as likely to drink heavily; Non-Hispanic whites who experienced child abuse or both ACE types were 1.5-2 times as likely to drink heavily; and Hispanics who experienced household challenges or both ACE types were 1.2 and 11 times as likely to report heavy drinking. ACEs impact depression and excessive alcohol use similarly across men and women. With the exception of heavy drinking, ACEs appear to have the same association with excessive alcohol use across race/ethnicity. It may be prudent to further investigate why the relationship between ACEs and heavy drinking may differ by race/ethnicity such that prevention strategies can be developed or refined to effectively address the needs of all sub-groups.

Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.

This study was to determine occupational exposures to formaldehyde and to compare concentrations of formaldehyde obtained by active and passive sampling methods. In one pathology and one histology laboratories, exposure measurements were collected with sets of active air samplers (Supelco LpDNPH tubes) and passive badges (ChemDisk Aldehyde Monitor 571). Sixty-six sample pairs (49 personal and 17 area) were collected and analyzed by NIOSH NMAM 2016 for active samples and OSHA Method 1007 (using the manufacturer's updated uptake rate) for passive samples. All active and passive 8-hour time-weighted average (TWA) measurements showed compliance with the OSHA permissible exposure limit (PEL-0.75 ppm) except for one passive measurement, whereas 78% for the active and 88% for the passive samples exceeded the NIOSH recommended exposure limit (REL-0.016 ppm). Overall, 73% of the passive samples showed higher concentrations than the active samples and a statistical test indicated disagreement between two methods for all data and for data without outliers. The OSHA Method cautions that passive samplers should not be used for sampling situations involving formalin solutions because of low concentration estimates in the presence of reaction products of formaldehyde and methanol (a formalin additive). However, this situation was not observed, perhaps because the formalin solutions used in these laboratories included much less methanol (3%) than those tested in the OSHA Method (up to 15%). The passive samplers in general overestimated concentrations compared to the active method, which is prudent for demonstrating compliance with an occupational exposure limit, but occasional large differences may be a result of collecting aerosolized droplets or splashes on the face of the samplers. In the situations examined in this study the passive sampler generally produces higher results than the active sampler so that a body of results from passive samplers demonstrating compliance with the OSHA PEL would be a valid conclusion. However, individual passive samples can show lower results than a paired active sampler so that a single result should be treated with caution.

We created a measure to help comprehend population vulnerability to potential flooding and excessive heat events using health, built environment and social factors. Through principal component analysis (PCA), we created non-weighted sum index scores of literature-reviewed social and built environment characteristics. We created baseline poor health measures using 1999-2005 age-adjusted cardiovascular and combined diabetes and hypertension mortality rates to correspond with social-built environment indices. We mapped US Census block groups by linked age-adjusted mortality and a PCA-created social-built environment index. The goal was to measure flooding and excessive heat event vulnerability as proxies for population vulnerability to climate change for Travis County, Texas. This assessment identified communities where baseline poor health, social marginalisation and built environmental impediments intersected. Such assessments may assist targeted interventions and improve emergency preparedness in identified vulnerable communities, while fostering resilience through the focus of climate change adaptation policies at the local level.

On October 27, 2014, CDC released guidance for monitoring and movement of persons with potential Ebola virus disease (Ebola) exposure in the United States. For persons with possible exposure to Ebola, this guidance recommended risk categorization, daily monitoring during the 21-day incubation period, and, for persons in selected risk categories, movement restrictions. The purpose of the guidance was to delineate methods for early identification of symptoms among persons at potential risk for Ebola so that they could be isolated, tested, and if necessary, treated to improve their chance of survival and reduce transmission. Within 7 days, all 50 states and two local jurisdictions (New York City [NYC] and the District of Columbia [DC]) had implemented the guidelines. During November 3, 2014-March 8, 2015, a total of 10,344 persons were monitored for up to 21 days with >99% complete monitoring. This public health response demonstrated the ability of state, territorial, and local health agencies to rapidly implement systems to effectively monitor thousands of persons over a sustained period.

Recent evidence has suggested the potential for wide-ranging health effects that could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF). In response, the National Institute for Occupational Safety and Health (NIOSH) set a recommended exposure limit (REL) for CNT and CNF: 1 microg m-3 as an 8-h time weighted average (TWA) of elemental carbon (EC) for the respirable size fraction. The purpose of this study was to conduct an industrywide exposure assessment among US CNT and CNF manufacturers and users. Fourteen total sites were visited to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone (PBZ) and area samples were collected for both the inhalable and respirable mass concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were collected at nine sites while at the remaining five sites both respirable and inhalable PBZ samples were collected side-by-side. Transmission electron microscopy (TEM) PBZ and area samples were also collected at the inhalable size fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 microg m-3 with a geometric mean (GM) of 0.34 microg m-3 and an 8-h TWA of 0.16 microg m-3. PBZ samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 microg m-3 with a GM of 1.21 microg m-3. PBZ samples analyzed by TEM showed concentrations ranging from 0.0001 to 1.613 CNT or CNF-structures per cm3 with a GM of 0.008 and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were found to be larger agglomerates in the 2-5 microm range as well as agglomerates >5 microm. A statistically significant correlation was observed between the inhalable samples for the mass of EC and structure counts by TEM (Spearman rho = 0.39, P < 0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were <1 mug m-3 at the respirable size fraction), while 30% of the inhalable PBZ EC samples were found to be >1 mug m-3. Until more information is known about health effects associated with larger agglomerates, it seems prudent to assess worker exposure to airborne CNT and CNF materials by monitoring EC at both the respirable and inhalable size fractions. Concurrent TEM samples should be collected to confirm the presence of CNT and CNF.

Chronic lower airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma, are currently the third leading cause of death in the United States. We aimed to evaluate changes in prevalence of and risk factors for COPD and asthma among the US adult population. We evaluated changes in prevalence of self-reported doctor-diagnosed COPD (i.e. chronic bronchitis and emphysema) and asthma and self-reported respiratory symptoms comparing data from the 1988-1994 and 2007-2010 National Health and Nutrition Examination Surveys. To investigate changes in the severity of each outcome over the two periods, we calculated changes in the proportions of spirometry-based airflow obstruction for each outcome. Prevalence of doctor-diagnosed chronic bronchitis and emphysema decreased significantly mainly among males, while asthma increased only among females. The self-reported disease and the respiratory symptoms were associated with increased prevalence of airflow obstruction for both periods. However, the prevalence of airflow obstruction decreased significantly in the second period among those with shortness of breath and doctor-diagnosed respiratory conditions (chronic bronchitis, emphysema, and asthma). COPD outcomes and asthma were associated with lower education, smoking, underweight and obesity, and occupational dusts and fumes exposure. Chronic lower airway diseases continue to be major public health problems. However, decreased prevalence of doctor-diagnosed chronic bronchitis and emphysema (in males) and decreased prevalence of airflow obstruction in those with respiratory symptoms and doctor-diagnosed respiratory diseases may indicate a declining trend and decrease in disease severity between the two periods. Continued focus on prevention of these diseases through public health interventions is prudent.

BACKGROUND: Predictors of death in hospitalized HIV-infected patients have not been previously reported in Bangladesh. OBJECTIVE: The primary aim of this study was to determine predictors of death among hospitalized HIV-infected patients at a large urban hospital in Bangladesh. METHODS: A study was conducted in the HIV in-patient unit (Jagori Ward) of icddr,b's Dhaka Hospital. Characteristics of patients who died during hospitalization were compared to those of patients discharged from the ward. Bivariate analysis was performed to determine associations between potential risk factors and death. Multivariable logistic regression was used to identify factors independently associated with death. RESULTS: Of 293 patients admitted to the Jagori Ward, 57 died during hospitalization. Most hospitalized patients (67%) were male and the median age was 35 (interquartile range: 2-65) years. Overall, 153 (52%) patients were diagnosed with HIV within 6 months of hospitalization. The most common presumptive opportunistic infections (OIs) identified were tuberculosis (32%), oesophageal candidiasis (9%), Pneumocystis jirovecii pneumonia (PJP) (8%), and histoplasmosis (7%). On multivariable analysis, independent predictors of mortality were CD4 count ≤200 cells/mm3 (adjusted odds ratio [aOR]: 16.6, 95% confidence interval [CI]: 3.7-74.4), PJP (aOR: 18.5, 95% CI: 4.68-73.3), oesophageal candidiasis (aOR: 27.5, 95% CI: 5.5-136.9), malignancy (aOR:15.2, 95% CI: 2.3-99.4), and bacteriuria (aOR:7.9, 95% CI: 1.2-50.5). Being on antiretroviral therapy prior to hospitalization (aOR: 0.2, 95% CI: 0.06-0.5) was associated with decreased mortality. CONCLUSION: This study showed that most patients who died during hospitalization on the Jagori Ward had HIV-related illnesses which could have been averted with earlier diagnosis of HIV and proper management of OIs. It is prudent to develop a national HIV screening programme to facilitate early identification of HIV.

Toxicologists are often called upon to assist in environmental, industrial, occupational and public health assessments. Accordingly, medical toxicologists may find it prudent to be aware of applicable federal toxicological regulations and reporting requirements and of the roles of relevant federal agencies. These regulations are numerous, complex, and have evolved and expanded over time, making it difficult for toxicologists to sustain a current knowledge base. This article reviews the pertinent federal toxicological reporting requirements with regards to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational Safety and Health Act, the Department of Transportation, and information about the National Response Center. We reference internet-based government resources and offer direct links to applicable websites in an attempt to offer rapid and current sources of practical information. The format of the article is a series of hypothetical scenarios followed by commentary. Discussions of the Safe Drinking Water Act and the Food, Drug, and Cosmetic Act and the Dietary Supplement Health and Education Act are beyond the scope of this paper. For those desiring a more in depth discussion of the relevant federal environmental laws and statutes, and applicable case law, the reader is directed to resources such as the Environmental Law Handbook, the websites of individual laws found at www.epa.gov and the decisions of individual courts of appeal. It is our hope that this article provides not only useful practical information for the practicing toxicologist, but also serves as a key reference for Medical Toxicology core content on environmental laws and regulations.

Toxicologists are often called upon to assist in environmental, industrial, occupational and public health assessments. Accordingly, medical toxicologists may find it prudent to be aware of applicable federal toxicological regulations and reporting requirements and of the roles of relevant federal agencies. These regulations are numerous, complex, and have evolved and expanded over time, making it difficult for toxicologists to sustain a current knowledge base. This article reviews the pertinent federal toxicological reporting requirements with regard to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational Safety and Health Act, the Department of Transportation, and information about the National Response Center. We reference internet-based government resources and offer direct links to applicable websites in an attempt to offer rapid and current sources of practical information. The format of the article is a series of hypothetical scenarios followed by commentary. Discussions of the Safe Drinking Water Act, the Food, Drug, and Cosmetic Act, and the Dietary Supplement Health and Education Act are beyond the scope of this paper. For those desiring a more in-depth discussion of the relevant federal environmental laws and statutes and applicable case law, the reader is directed to resources such as the Environmental Law Handbook, the websites of individual laws found at www.epa.gov and the decisions of individual courts of appeal. It is our hope that this article provides not only useful practical information for the practicing toxicologist but also serves as a key reference for medical toxicology core content on environmental laws and regulations.

BACKGROUND: Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung cancer risks associated with chronic pulmonary exposure to single-walled (SW) CNT through the fundamental understanding of cellular and molecular processes leading to carcinogenesis. We hypothesized that the acquisition of cancer stem cells (CSC), a subpopulation that drive tumor initiation and progression, may contribute to CNT carcinogenesis. METHODS: Non-tumorigenic human lung epithelial cells were chronically exposed to well-dispersed SWCNT for a period of 6 months at the physiologically relevant concentration of 0.02 mug/cm2 surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of CSC-like cells under CSC-selective conditions of tumor spheres and side population (SP). CSC-like cells were isolated using fluorescence-activated cell sorting and were assessed for aggressive behaviors, including acquired apoptosis resistance and increased cell migration and invasion in vitro, and tumor-initiating capability in vivo. Non-small cell lung cancer cells served as a positive control. RESULTS: We demonstrated for the first time the existence of CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells. These CSC-like cells, in contrary to their non-CSC counterpart, possessed all biological features of lung CSC that are central to irreversible malignant transformation, self-renewal, aggressive cancer behaviors, and in vivo tumorigenesis. These cells also displayed aberrant stem cell markers, notably Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53 abrogated CSC properties of CSC-like cells. Furthermore, we identified specific stem cell surface markers CD24low and CD133high that are associated with SWCNT-induced CSC formation and tumorigenesis. CONCLUSIONS: Our findings provide new and compelling evidence for the acquisition of CSC-like cells induced by chronic SWCNT exposure, which are likely to be a major driving force for SWCNT tumorigenesis. Thus, our study supports prudent adoption of prevention strategies and implementation of exposure control for SWCNT. We also suggest that the detection of CSC and associated surface markers may provide an effective screening tool for prediction of the carcinogenic potential of SWCNT and related nanoparticles.

Organizations around the world have called for the responsible development of nanotechnology. The goals of this approach are to emphasize the importance of considering and controlling the potential adverse impacts of nanotechnology in order to develop its capabilities and benefits. A primary area of concern is the potential adverse impact on workers, since they are the first people in society who are exposed to the potential hazards of nanotechnology. Occupational safety and health criteria for defining what constitutes responsible development of nanotechnology are needed. This article presents five criterion actions that should be practiced by decision-makers at the business and societal levels-if nanotechnology is to be developed responsibly. These include (1) anticipate, identify, and track potentially hazardous nanomaterials in the workplace; (2) assess workers' exposures to nanomaterials; (3) assess and communicate hazards and risks to workers; (4) manage occupational safety and health risks; and (5) foster the safe development of nanotechnology and realization of its societal and commercial benefits. All these criteria are necessary for responsible development to occur. Since it is early in the commercialization of nanotechnology, there are still many unknowns and concerns about nanomaterials. Therefore, it is prudent to treat them as potentially hazardous until sufficient toxicology, and exposure data are gathered for nanomaterial-specific hazard and risk assessments. In this emergent period, it is necessary to be clear about the extent of uncertainty and the need for prudent actions.

Disasters often set the stage for scientific inquiry within the fieid of occupational safety and health. This is especially true when the long-term consequences of exposures associated with a particular disaster are unclear. However, a responder research study can be costly and difficult to design, and researchers must consider whether the proposed study will produce useful, reliable results and is a prudent public health investment. The decision process can be segregated into various components, including scientific rationale that should be formally recognized as critical to efficiently and effectively determine whether a research study is warranted. The scientific rationale includes certain controlling or "gatekeeper" factors that should be present to proceed with research.

BACKGROUND: Prudent antibiotic prescribing practices are essential to limiting antibiotic resistance. OBJECTIVE: To assess the trend in percentage of office visits for acute respiratory infections (ARIs) linked with an antibiotic prescription. METHODS: Retrospective analysis of Montana Medicaid billing claims data for each year, 1999 to 2010, was done. Participants included continuously enrolled children aged ≤14 years. Primary outcomes were ARI-related office visits and filled antibiotic prescriptions within 10 days of the office visit. RESULTS: Of the 873,244 office visits identified, 116,962 (13%) had an ARI as the primary diagnosis. Among ARI-related office visits, 64,250 (55%) were linked with an antibiotic prescription. From 1999 to 2010, the odds of ARI-related visits being linked with an antibiotic prescription did not change (odds ratio = 1.00; 95% confidence interval = 0.995-1.002). CONCLUSIONS: The percentage of ARI-related visits linked with an antibiotic prescription did not decrease from 1999 to 2010. Further efforts are needed to reduce antibiotic treatment for ARIs.

BACKGROUND: Bronchiolitis obliterans, an irreversible lung disease, was first associated with inhalation of butter flavorings (diacetyl) in workers at a microwave popcorn company. Excess rates of lung-function abnormalities were related to cumulative diacetyl exposure. Because information on potential excess mortality would support development of permissible exposure limits for diacetyl, we investigated respiratory-associated mortality during 2000-2011 among current and former workers at this company who had exposure to flavorings and participated in cross-sectional surveys conducted between 2000-2003. METHODS: We ascertained workers' vital status through a Social Security Administration search. Causes of death were abstracted from death certificates. Because bronchiolitis obliterans is not coded in the International Classification of Disease 10 revision (ICD-10), we identified respiratory mortality decedents with ICD-10 codes J40-J44 which encompass bronchitis (J40), simple and mucopurulent chronic bronchitis (J41), unspecified chronic bronchitis (J42), emphysema (J43), and other chronic obstructive pulmonary disease (COPD) (J44). We calculated expected number of deaths and standardized mortality ratios (SMRs) with 95% confidence intervals (CI) to determine if workers exposed to diacetyl experienced greater respiratory mortality than expected. RESULTS: We identified 15 deaths among 511 workers. Based on U.S. population estimates, 17.39 deaths were expected among these workers (SMR = 0.86; CI:0.48-1.42). Causes of death were available for 14 decedents. Four deaths among production and flavor mixing workers were documented to have a multiple cause of 'other COPD' (J44), while 0.98 'other COPD'-associated deaths were expected (SMR = 4.10; CI:1.12-10.49). Three of the 4 'other COPD'-associated deaths occurred among former workers and workers employed before the company implemented interventions reducing diacetyl exposure in 2001. CONCLUSION: Workers at the microwave popcorn company experienced normal rates of all-cause mortality but higher rates of COPD-associated mortality, especially workers employed before the company reduced diacetyl exposure. The demonstrated excess in COPD-associated mortality suggests continued efforts to lower flavoring exposure are prudent.