INTRODUCTION: Timely and relevant data are critical to monitoring the rapidly changing youth vaping epidemic and for understanding the prevalence, patterns of use, knowledge, and perceptions of tobacco products. While e-cigarettes have been the most used tobacco product among youth for nearly a decade, new nicotine delivery products continue to be introduced to the US market. Flavored tobacco products, including flavored e-cigarettes, menthol cigarettes, and flavored cigars, drive disparities in use by young people. AIMS AND METHODS: To examine tobacco use among youth and young adults, the Monitoring E-Cigarette Use among Youth project established a longitudinal cohort of youth and young adults (13-24)-the Tobacco Epidemic Evaluation Network (TEEN+) study. TEEN+ focuses on e-cigarette and other tobacco products use and also includes questions about other substance use (eg, marijuana, alcohol), physical health, mental health, and social determinants of health (eg, discrimination, poverty, sexual and gender identity). Geocoding of responses allows for the evaluation of local tobacco control policies. The cohort includes an oversample of California residents to generate reliable and representative state-level estimates. This manuscript provides an overview of methods and baseline demographics from Wave 1. RESULTS: The initial Wave 1 TEEN+ cohort included 10 255 in the national sample and 2761 in the California sample. CONCLUSIONS: TEEN+ study data complement nationally-representative cross-sectional studies and allow for rapid evaluation of local and state policies. This manuscript describes the study's probability-based sample recruitment. Furthermore, we identify this initiative as a resource for evaluating the impact of flavored tobacco restriction policies and informing policy implementation efforts. IMPLICATIONS: This manuscript provides an overview of the methodology and baseline characteristics for a new longitudinal cohort of youth and young adults, the Tobacco Epidemic Evaluation Network (TEEN+) study. The TEEN+ study data can be used to evaluate the impact of flavored tobacco product restriction policies and informing policy implementation efforts.

E-cigarette products, related policies, and use patterns change rapidly. In the United States, the prevalence of e-cigarette use is markedly higher among youths and young adults than it is among adults overall. In 2021, 4.5% of all adults aged ≥18 years (an estimated 11.1 million) and 11.0% of young adults aged 18-24 years (an estimated 3.1 million) currently (≥1 day during the previous 30 days) used e-cigarettes; during 2022, 14.1% of high school students (an estimated 2.14 million) currently used e-cigarettes (1,2). E-cigarettes often contain high concentrations of nicotine. Nicotine is highly addictive and can harm the adolescent brain, which continues to develop through approximately age 25 years (3). Since 2020, the availability of e-cigarette products has changed in response to multiple factors, including local and state policies to address flavored e-cigarette sales, actions undertaken by the Food and Drug Administration (FDA), COVID-19-related closures, and global supply chain disruptions. To assess trends in unit sales of e-cigarettes in the United States, by product and flavor, and top-selling brands, the CDC Foundation, Truth Initiative,* and CDC analyzed retail scanner data during January 26, 2020-December 25, 2022, from Information Resources, Inc. (IRI), a U.S. data analytics and market research company. Overall, unit sales increased by 46.6% during the study period. The unit share of menthol-flavored product sales remained relatively stable during this period, whereas nonmenthol flavor unit shares changed. During January 26, 2020-December 25, 2022, unit shares of tobacco-flavored and mint-flavored products decreased (from 28.4% to 20.1% and from 10.1% to 5.9%, respectively), whereas shares of other flavor sales increased (from 29.2% to 41.3%). In addition, during January 2020-December 2022, unit shares of prefilled cartridges decreased from 75.2% to 48.0%, and disposable e-cigarette unit share increased from 24.7% to 51.8% of total unit sales. The five top-selling e-cigarette brands for the 4-week period ending December 25, 2022, were Vuse, JUUL, Elf Bar, NJOY, and Breeze Smoke. Analysis of information on e-cigarette retail sales can guide strategies to prevent youth access to and use of e-cigarettes, including restrictions on flavored tobacco products (4).

AIMS: To evaluate statewide policies restricting e-cigarette nicotine strength. DESIGN: A difference-in-difference regression analysis was used to compare e-cigarette sales in states that restrict nicotine strength with states with no restrictions. Since flavor restrictions might affect sales and nicotine strength, states with flavor restrictions were also assessed. SETTING AND CASES: United States e-cigarette retail sales data during January 2017-March 2022 were licensed from Information Resources Incorporated. States with restrictions included Massachusetts (restricted maximum nicotine strength to 3.5% and non-tobacco flavored e-cigarette sales in December 2019); Utah (restricted nicotine strength to 3.6% in September 2021); and Rhode Island, New York, and Washington (restricted non-tobacco flavor sales in October 2019, May 2020, and October 2019-January 2020 respectively). These were compared with data from 34 states with no e-cigarette nicotine strength or flavor restrictions MEASUREMENTS: Weighted mean nicotine strength and total unit sales. Total unit sales per 1,000 state population were summed into 4-week periods by state. Models controlled for emergency responses, state demographics, tobacco control policies, time, and state fixed effects. FINDINGS: Restricting both nicotine strength and flavors in Massachusetts was associated with a 2.04 percentage point (pp) reduction in mean nicotine strength and 86.76-unit reduction in monthly unit sales per 1,000 persons compared with states with no restrictions (all p<0.01). Restricting nicotine strength only in Utah was associated with a 1.77 pp (p<0.01) reduction in mean nicotine strength; however, there was no impact on unit sales. Restricting non-tobacco flavor sales only in Rhode Island, New York, and Washington slightly reduced mean nicotine strength (0.21, 0.62, and 0.19 pp, respectively) and sales (36.66, 34.51, and 16.37 units, respectively) (all p<0.01). CONCLUSIONS: US statewide policies restricting e-cigarette nicotine strength appear to be associated with reductions in average nicotine strength in sales within that state; however, there appears to be no impact on unit sales. When these policies are implemented along with flavor restrictions; reductions in average nicotine strength occur in addition to reduced unit sales.

BACKGROUND: E-cigarettes are the most-commonly used tobacco product by youth since 2014. To prevent youth access and use of e-cigarettes, many U.S. states and localities have enacted policies over a relatively short period of time. The adoption of these policies has necessitated timely data collection to evaluate impacts. METHODS: To assess the impact of flavored e-cigarette policies in select states and local jurisdictions across the United States, a multi-method, complementary approach was implemented from July 2019 to present, which includes analyses of cross-sectional online surveys of young people ages 13-24 years with retail sales data. RESULTS: From February 2020 through February 2023, cross-sectional surveys have been conducted in three cities, one county, and eight states where policy changes have been enacted or are likely to be enacted. Data collection occurred every six months to provide near real-time data and examine trends over time. Additionally, weekly retail sales data were aggregated to showcase monthly sales trends at the national level and for the selected states. DISCUSSION: This rapid and efficient method of coupling online survey data with retail sales data provides a timely and effective approach for monitoring a quickly changing tobacco product landscape, particularly for states and localities where rapidly-available data is often not available. This approach can also be used to monitor other health behaviors and relevant policy impacts.

OBJECTIVE: Sexually transmitted infections (STIs) increase mucosal HIV infection risk and have the potential to reduce preexposure prophylaxis efficacy. Clinical trials of a broadly neutralizing antibody (bNAb) provided proof-of-concept that passive immunization against HIV can be efficacious in people. We sought to evaluate preclinically the protective efficacy of passive bNAb immunization against simian-human immunodeficiency virus (SHIV) infection in the context of concurrent vaginal STIs. DESIGN: Using a macaque model of combined ulcerative and nonulcerative vaginal STIs caused by Treponema pallidum, Chlamydia trachomatis, and Trichomonas vaginalis, we determined the protection that passively administered bNAb 10-1074 conferred against repeated vaginal SHIV challenges and compared correlates of protection to contemporaneous and historical controls without STIs. METHODS: Plasma viremia was monitored via RT-qPCR assay. Concentrations of 10-1074 were determined longitudinally in plasma samples via TZM-bl pseudovirus neutralization assay. RESULTS: Among macaques with vaginal STIs, a single subcutaneous injection of 10-1074 durably protected against vaginal SHIV acquisition, as compared with untreated controls. Interestingly, the median plasma concentration of 10-1074 at the time of SHIV breakthrough among macaques with STIs was significantly higher (10-fold) than that previously observed among 10-1074-treated macaques in the absence of STIs. CONCLUSION: Passive immunization with 10-1074 conferred significant protection against repeated vaginal SHIV challenges among macaques harboring vaginal STIs. However, our findings suggest that higher bNAb concentrations may be required for prophylaxis when STIs are present. Our findings potentially impact dose selection for the clinical development of bNAbs and highlight the importance of additional preclinical efficacy testing in STI models.

INTRODUCTION: The e-cigarette market has expanded considerably in recent years, resulting in changes in availability and use of e-cigarettes with varying characteristics. AIMS AND METHODS: This study assessed trends in sales and prices of e-cigarettes by nicotine strength level, including by product type and flavor, during January 2017-March 2022. US e-cigarette retail sales data were licensed from IRI company. Nicotine strength was categorized as: <1%; 1% to <2%; 2% to <3%; 3% to <4%; 4% to <5%; ≥5%. E-cigarette flavors were categorized as tobacco, menthol, mint, or other flavors. Product type was categorized as prefilled cartridge devices, disposable devices, or e-liquid bottles. Trend analyses were performed using Joinpoint Regression. RESULTS: During January 2017-March 2022, the unit share of products containing ≥5% nicotine strength increased by 1486.3%, while the dollar share increased by 1345.5%. By March 2022, 80.9% of total unit sales were composed of products containing ≥5% nicotine strength. By flavor, the percentage of units sold with ≥5% nicotine strength was 61.3% of tobacco-flavor sales, 79.3% of menthol sales, 87.4% of mint sales, and 96.1% of other flavor sales. By product type, the percentage of units sold with ≥5% nicotine strength was 90.6% of disposable e-cigarette sales and 74.2% of prefilled cartridge sales. During January 2017-March 2022, the price of low-nicotine strength e-cigarettes increased, while the price of high-nicotine products either decreased or did not change. CONCLUSIONS: Sales of high nicotine-strength e-cigarettes have dominated the US e-cigarette market. Limiting the nicotine strength of e-cigarettes could be considered as part of a comprehensive tobacco control strategy to reduce youth access to and use of these products. IMPLICATIONS: The findings from this study indicate that previously reported increases in e-cigarette nicotine strength during 2013-2018 have continued through 2022. The US e-cigarette market sales continue to be dominated by relatively high-nicotine products. Strategies to address factors that make these products, particularly appealing to youth, including flavors and product innovations, are critical. Such strategies are important-as part of a comprehensive approach alongside other evidence-based population-level actions-to address youth e-cigarette use. Importantly, actions to reduce e-cigarette use among youth are not mutually exclusive from actions to maximize the potential benefits of e-cigarettes for increasing smoking cessation among adults.

BACKGROUND: In June 2020, Massachusetts implemented a law prohibiting the sale of all flavored tobacco products, including menthol cigarettes. This law was associated with significant declines in overall cigarette and menthol cigarette sales in Massachusetts, however it is unknown whether the law has increased cross-border sales in neighboring states where menthol cigarettes are still sold. METHODS: U.S. cigarette retail scanner data were licensed from the IRi Company. Cigarette pack sales were summed in 4-week periods during January 2020-December 2021 (n = 832). Outcomes were state-level pack sales per 1000 population, overall and by flavor status (menthol and non-flavored). A difference-in-differences analysis was used to examine adjusted sales for Massachusetts border states (New Hampshire, Connecticut, Vermont, and Rhode Island) before (January 2020-May 2020) and after (June 2020-December 2021) the Massachusetts's law, compared to 28 non-border states. Control variables included state and time fixed effects; real price per pack; tobacco control policies; COVID-19 cases and deaths, and related statewide closure; and state sociodemographic characteristics. RESULTS: Following the law, unadjusted sales of menthol, non-flavored, and overall cigarettes trended upward in border states; however, these increases were not statistically significant or different from sales patterns in non-border states. This finding persisted after accounting for product prices, tobacco control policies, the COVID-19 pandemic, sociodemographic factors, and fixed effects. CONCLUSION: Laws prohibiting the sale of flavored tobacco products, including menthol products, reduce access to these products, while having no significant impact on cross-border sales in neighboring states where menthol cigarettes are sold.

OBJECTIVE: Flavours that produce a cooling sensation, such as menthol, enhance the appeal of e-cigarettes among youth; but not all e-cigarettes that produce cooling sensations are labelled as menthol. This study assessed trends in unit sales of cooling flavoured e-cigarettes in the USA. DESIGN: E-cigarette retail sales during 26 January 2017 to 28 November 2021 were licensed from Information Resources, Inc, which records brick-and-mortar retail scanner sales but not online or vape shop sales. Cooling flavours were identified using six descriptors: menthol, ice, cool, chill, freeze or frost; ambiguous flavours were verified using online searches. Cooling flavours were categorised by characterising flavour (menthol, mint, other) and product type (prefilled cartridges, disposables, e-liquids). Joinpoint regression was used to assess sales and price trends. RESULTS: During January 2017 to November 2021, unit sales of cooling flavoured e-cigarettes increased by 693.0% (1.5 to 12.0 million units); the percentage of these sales from total sales increased from 26.4% to 54.9%. Among cooling flavours, percentage of menthol sales decreased from 94.5% to 73.0% (p<0.001). Among menthol cooling flavours, percentage of prefilled cartridges increased from 67.2% to 96.6% (p<0.001); among non-menthol cooling flavours, percentage of disposable e-cigarettes increased from 5.2% to 99.2% (p<0.001). There were no significant price differences between cooling and non-cooling flavoured disposable e-cigarettes. CONCLUSION: The percentage of cooling flavoured e-cigarette sales from total sales doubled during 2017-2021, and sales of non-menthol cooling disposable e-cigarettes experienced the highest percentage increase. Cooling flavoured e-cigarettes are important to consider when developing strategies to address flavoured e-cigarette use among youth.

In the past 15 years, the tobacco product landscape has evolved rapidly. After the introduction of E-cigarettes in the 2000s and the growth and promotion of several brands, including JUUL, the use of these products rapidly increased among U.S. youth during 20112019.1, 2, 3 These increases were driven by multiple factors, including advertising themes that are similar to those previously found to promote youth cigarette smoking,4 flavors that appeal to youth,5 and the introduction of newer products with characteristics that appeal to young people (e.g., smaller and easily concealable or similar in size and shape to a USB flash drive). Newer E-cigarette types also deliver nicotine in the form of nicotine salts, which allows a particularly high level of nicotine to be inhaled more easily and with less irritation than the free-base nicotine that has traditionally been used in conventional tobacco products and older E-cigarette types.6 However, the diversification of the tobacco product landscape has not been limited to E-cigarettes, and other products also continue to reemerge or newly emerge. More recently, updated versions of heated tobacco products, which were originally introduced in the 1990s with limited consumer interest, have returned to the marketplace in several countries.7,8 Novel smokeless tobacco products,9 including nicotine pouches, have also recently emerged; these prefilled, microfiber pouches contain nicotine powder that dissolves in the mouth without requiring spitting. Given the quickly evolving tobacco product marketplace, it is critical that researchers rapidly collect data on these emerging products, particularly to document seminal increases in sales and use to inform timely public health interventions that can expeditiously mitigate the use among populations at increased risk, including young people.

IMPORTANCE: e-Cigarettes are the most commonly used tobacco product among US youths. Flavors are among the most cited reasons for use of e-cigarettes among youths, and therefore, some states have imposed restrictions on flavored e-cigarette sales. To our knowledge, no study has compared e-cigarette sales between states with statewide flavored e-cigarette restrictions and states without such restrictions while controlling for co-occurring events. OBJECTIVE: To assess whether implementation of statewide restrictions on flavored e-cigarette sales in Massachusetts, New York, Rhode Island, and Washington was associated with a reduction in total e-cigarette unit sales from 2014 to 2020. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study with difference-in-differences analysis used e-cigarette retail sales data from Massachusetts, Rhode Island, and Washington, which implemented restrictions on flavored e-cigarette sales in October 2019; New York, which implemented these restrictions in May 2020; and 35 states without these restrictions (control states). Sales were summed into 4-week periods from August 24, 2014, to December 27, 2020, for a total of 2988 state-period observations. MAIN OUTCOMES AND MEASURES: A difference-in-differences analysis was conducted to compare e-cigarette unit sales in the 4 states with flavor restrictions (before and after implementation) with those in the 35 control states. The model controlled for other population-based policies and emergent events (eg, the COVID-19 pandemic). Data on 4-week e-cigarette unit sales were sorted into 4 flavor categories (tobacco, menthol, mint, and other). Unit sales were standardized to reflect the most common package sizes for each product type. RESULTS: Statewide restrictions on non-tobacco-flavored e-cigarette sales were associated with the following reductions in mean 4-week total e-cigarette sales in intervention states compared with control states from October 2019 to December 2020: 30.65% (95% CI, 24.08%-36.66%) in New York, 31.26% (95% CI, 11.94%-46.34%) in Rhode Island, and 25.01% (95% CI, 18.43%-31.05%) in Washington. In Massachusetts, the comprehensive sales prohibition of all e-cigarette products was associated with a 94.38% (95% CI, 93.37%-95.23%) reduction in 4-week sales compared with control states. Except in Massachusetts, where all sales of flavored e-cigarettes decreased, reductions were found only for non-tobacco-flavored e-cigarette sales in the other states with restrictions. Among control states, mean sales decreased by 28.4% from August 2019 to February 2020 but then increased by 49.9% from February through December 2020. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, statewide restrictions on the sale of flavored e-cigarettes in Massachusetts, New York, Rhode Island, and Washington were associated with a reduction in total e-cigarette sales. These findings suggest that not all e-cigarette users who purchased non-tobacco-flavored e-cigarettes switched to purchasing tobacco-flavored e-cigarettes after policy implementation.

OBJECTIVE: The opioid epidemic has increased parentally acquired HIV infection. To inform the development of a long-acting prevention strategy, we evaluated the protective efficacy of broadly neutralizing antibodies (bNAbs) against intravenous SHIV infection in macaques. DESIGN: Five cynomolgus macaques were injected once subcutaneously with 10-1074 and 3BNC117 (10 mg each kg-1) and were repeatedly challenged intravenously once weekly with SHIVAD8-EO (130 TCID50), until infection was confirmed via plasma viral load assay. Two control macaques, which received no antibody, were challenged identically. METHODS: Plasma viremia was monitored via RT-qPCR assay. bNAb concentrations were determined longitudinally in plasma samples via TZM-bl neutralization assays using virions pseudotyped with 10-1074-sensitive (X2088_c9) or 3BNC117-sensitive (Q769.d22) HIV envelope proteins. RESULTS: Passively immunized macaques were protected against a median of five weekly intravenous SHIV challenges, as compared to untreated controls, which were infected following a single challenge. Of the two bNAbs, 10-1074 exhibited relatively longer persistence in vivo. The median plasma level of 10-1074 at SHIV breakthrough was 1.1 μg ml-1 (range: 0.6-1.6 μg ml-1), whereas 3BNC117 was undetectable. Probit modeling estimated that 6.6 μg ml-1 of 10-1074 in plasma corresponded to a 99% reduction in per-challenge infection probability, as compared to controls. CONCLUSIONS: Significant protection against repeated intravenous SHIV challenges was observed following administration of 10-1074 and 3BNC117 and was due primarily to 10-1074. Our findings extend preclinical studies of bNAb-mediated protection against mucosal SHIV acquisition and support the possibility that intermittent subcutaneous injections of 10-1074 could serve as long-acting pre-exposure prophylaxis for persons who inject drugs.

Since electronic cigarettes (e-cigarettes) entered the U.S. marketplace in 2007, the landscape has evolved to include different product types (e.g., prefilled cartridge-based and disposable products) and flavored e-liquids (e.g., fruit, candy, mint, menthol, and tobacco flavors), which have contributed to increases in youth use (1,2). E-cigarettes have been the most commonly used tobacco product among U.S. youths since 2014; in 2019, 27.5% of high school students reported current e-cigarette use (3). To assess trends in unit sales of e-cigarettes in the United States by product and flavor type, CDC, CDC Foundation, and Truth Initiative analyzed retail scanner data during September 14, 2014-May 17, 2020, from Information Resources, Inc. (IRI). During this period, total e-cigarette sales increased by 122.2%, from 7.7 million to 17.1 million units per 4-week interval. By product type, the proportion of total sales that was prefilled cartridge products increased during September 2014-August 2019 (47.5% to 89.4%). During August 2019-May 2020, the proportion of total sales that was disposable products increased from 10.3% to 19.8%, while the proportion that was prefilled cartridge products decreased (89.4% to 80.2%). Among prefilled cartridge sales, the proportion of mint sales increased during September 2014-August 2019 (<0.1% to 47.6%); during August 2019-May 2020, mint sales decreased (47.6% to 0.3%), as menthol sales increased (10.7% to 61.8%). Among disposable e-cigarette sales during September 2014-May 2020, the proportion of mint sales increased (<0.1% to 10.5%), although tobacco-flavored (52.2% to 17.2%) and menthol-flavored (30.3% to 10.2%) sales decreased; during the same period, sales of all other flavors combined increased (17.2% to 62.1%). E-cigarette sales increased during 2014-2020, but fluctuations occurred overall and by product and flavor type, which could be attributed to consumer preferences and accessibility. Continued monitoring of e-cigarette sales and use is critical to inform strategies at the national, state, and community levels to minimize the risks of e-cigarettes on individual- and population-level health. As part of a comprehensive approach to prevent and reduce youth e-cigarettes use, such strategies could include those that address youth-appealing product innovations and flavors.

Accumulation of float coal dust (FCD) in underground mines is an explosion hazard that affects all underground coal mine workers. While this hazard is addressed by the application of rock dust, inadequate rock dusting practices can leave miners exposed to an explosion risk. Researchers at the National Institute for Occupational Safety and Health (NIOSH) have focused on developing a water curtain that removes FCD from the airstream, thereby reducing the buildup of FCD in mine airways. In this study, the number and spacing of the active sprays in the water curtain were varied to determine the optimal configuration to obtain peak knockdown efficiency (KE) while minimizing water consumption.

Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 mug ml(-1) correlated with >/=99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.

Contaminants such as heavy metals may contribute to the dissemination of antimicrobial resistance (AMR) by enriching resistance gene determinants via co-selection mechanisms. In the present study, a survey was performed on soils collected from four areas at the Savannah River Site (SRS), South Carolina, USA, with varying contaminant profiles: relatively pristine (Upper Three Runs), heavy metals (Ash Basins), radionuclides (Pond B) and heavy metal and radionuclides (Tim's Branch). Using 16S rRNA gene amplicon sequencing, we explored the structure and diversity of soil bacterial communities. Sites with legacies of metal and/or radionuclide contamination displayed significantly lower bacterial diversity compared to the reference site. Metagenomic analysis indicated that multidrug and vancomycin antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) including those associated with copper, arsenic, iron, nickel and zinc were prominent in all soils including the reference site. However, significant differences were found in the relative abundance and diversity of certain ARGs and MRGs in soils with metal/radionuclide contaminated soils compared to the reference site. Co-occurrence patterns revealed significant ARG/MRG subtypes in predominant soil taxa including Acidobacteriaceae, Bradyrhizobium, Mycobacterium, Streptomyces, Verrumicrobium, Actinomadura and Solirubacterales. Overall, the study emphasizes the potential risk of human activities on the dissemination of AMR in the environment.

The ability to detect, quantify, and interrogate the properties of immune responses raised against biological therapeutics is not only important to our understanding of these molecules, but also to their success in the clinic. A tiered assay approach to identify the presence, specificity, and titer of anti-drug antibody (ADA) responses has been adopted as a gold standard by industry leaders, the FDA, and the EMA. In order to support pre-clinical and clinical trials, these assays must be standardized, and their performance sufficiently characterized to ensure the accuracy and reproducibility of results under relevant testing conditions. Here we present implementation of electrochemiluminiscence assays that fit into the tiered paradigm of ADA testing for five HIV broadly neutralizing antibodies (3NC117, 3BNC117-LS, 10-1074, PGT121, and PGDM1400) in compliance with Good Clinical Laboratory practices. Assay sensitivities and matrix effects were evaluated and used to inform the development of positivity cut points. Once cut points were established, assay precision, specificity, free-drug tolerance, and robustness were defined. In all cases, assay characteristics met or surpassed recommendations set forth by the FDA. To further evaluate the performance of these assays and the tiered approach, samples from non-human primates that had received a subset of the five therapeutics were evaluated. In sum, this study reports qualification of a set of ADA assays available to the scientific community as pre-clinical and clinical trials of broadly HIV-neutralizing antibodies proceed, and a framework that is easily adapted as new drug products are advanced in the clinic.

The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. As with any protein therapeutic drug product, it is imperative to have qualified assays that can accurately detect and quantify anti-drug antibodies (ADA) that may develop in patients receiving passive administration of HIV-1 bnAbs. Here, we have optimized and qualified a functional assay to assess the potential of ADA to inhibit the neutralizing function of HIV-1 bnAbs. Using a modified version of the validated TZM-bl HIV-1 neutralization assay, murine anti-idiotype antibodies were utilized to optimize and evaluate parameters of linearity, range, limit of detection, specificity, and precision for measuring inhibitory ADA activity against multiple HIV-1 bnAbs that are in clinical development. We further demonstrate the utility of this assay for detecting naturally occurring ADA responses in non-human primates receiving passive administration of human bnAbs. This functional assay format complements binding-antibody ADA strategies being developed for HIV-1 bnAbs, and when utilized together, will support a multi-tiered approach for ADA testing that is compliant with Good Clinical Laboratory Practice (GCLP) procedures and FDA guidance.

OBJECTIVE: Active surveillance (AS) is an increasingly utilized strategy for monitoring men with low-risk prostate cancer (PCa) that allows them to defer active treatment (AT) in the absence of cancer progression. Studies have explored reasons for selecting AS and for then switching to AT, but less is known about men's experiences being on AS. We interviewed men to determine the clinical and psychological factors associated with selecting and adhering to AS protocols. METHODS: We conducted semi-structured interviews with men with a low-risk PCa at two academic medical centers. Subjects had either been on AS for >/= 1 year or had opted for AT after a period of AS. We used an iterative, content-driven approach to analyze the interviews and to identify themes. RESULTS: We enrolled 21 subjects, mean age 70.4 years, 3 racial/ethnic minorities, and 16 still on AS. Men recognized the favorable prognosis of their cancer (some had sought second opinions when initially offered AT), valued avoiding treatment complications, were reassured that close monitoring would identify progression early enough to be successfully treated, and trusted their urologists. Although men reported feeling anxious around the time of surveillance testing, those who switched to AT did so based only on evidence of cancer progression. CONCLUSIONS: Our selected sample was comfortable being on AS because they understood and valued the rationale for this approach. However, this highlights the importance of ensuring that men newly diagnosed with a low-risk PCa are provided sufficient information about prognosis and treatment options to make informed decisions.

The cloud and aerosol spectrometer (CAS) was calibrated to enable CAS sizing of coal dust for studies on flammable dust control. Coal dust sizes were determined by light-scattering theories for irregular particles that account for particle composition and morphology in computing coal dust diameters. Coal dust size computations were compared with test dust that was generated by cyclone separation and air-jet sieving and characterized by aerodynamic particle sizer (APS) and computer-controlled scanning electron microscopy (CCSEM) measurements. For test dust in the range of 0.5–32 μm, coal dust size distributions were consistent with cyclone-separated and sieve-segregated sizes. For the 3–20 μm size range, the coal dust size distribution had a mass median diameter that was 14% larger than that of the APS. This difference was reasonable considering that the basic calibration for glass spheres had 13% uncertainty. For the 20–32 μm and 32–45 μm test dusts, mass median diameters differed from CCSEM measurements by only 4% and 5%, respectively. Overall, the results suggest agreement between test dust sizes and computations for coal dust. Alternatively, using conventional Mie theory computations for spheres, coal dust mass median diameters were 35% and 40% larger than APS and CCSEM measurements, respectively.

BACKGROUND: Four wild polio-virus cases were reported in Borno State, Nigeria 2016, 1 year after Nigeria had been removed from the list of polio endemic countries by the World Health Organization. Resulting from Nigeria's decade long conflict with Boko Haram, health officials had been unable to access as much as 60% of the settlements in Borno, hindering vaccination and surveillance efforts. This lack of accessibility made it difficult for the government to assess the current population distribution within Borno. This study aimed to use high resolution, visible band satellite imagery to assess the habitation of inaccessible villages in Borno State. METHODS: Using high resolution (31-50 cm) imagery from DigitalGlobe, analysts evaluated the habitation status of settlements in Borno State identified by Nigeria's Vaccination Tracking System. The analysts looked at imagery of each settlement and, using vegetation (overgrowth vs. cleared) as a proxy for human habitation, classified settlements into three categories: inhabited, partially abandoned, and abandoned. Analysts also classified the intact percentage of each settlement starting at 0% (totally destroyed since last assessment) and increasing in 25% intervals through 100% (completely intact but not expanded) up to 200+% (more than doubled in size) by looking for destroyed buildings. These assessments were then used to adjust previously established population estimates for each settlement. These new population distributions were compared to vaccination efforts to determine the number of children under 5 unreached by vaccination teams. RESULTS: Of the 11,927 settlements assessed 3203 were assessed as abandoned (1892 of those completely destroyed), 662 as partially abandoned, and 8062 as fully inhabited as of December of 2017. Comparing the derived population estimates from the new assessments to previous assessment and the activities of vaccination teams shows that an estimated 180,155 of the 337,411 under five children who were unreached in 2016 were reached in 2017 (70.5% through vaccination efforts in previously inaccessible areas, 29.5% through displacement to accessible areas). CONCLUSIONS: This study's methodology provides important planning and situation awareness information to health workers in Borno, Nigeria, and may serve as a model for future data gathering efforts in inaccessible regions.

Routine immunization coverage in Nigeria is suboptimal. In the northwestern state of Sokoto, an independent population-based survey for 2016 found immunization coverage with the third dose of Pentavalent vaccine to be 3%, whereas administrative coverage in 2016 was reported to be 69%. One possibility driving this large discrepancy is that administrative coverage is calculated using an under-estimated target population. Official population projections from the 2006 Census are based on state-specific standard population growth rates. Immunization target population estimates from other sources have not been independently validated. We conducted a micro-census in Magarya ward, Wurno Local Government Area of Sokoto state to obtain an accurate count of the total population living in the ward, and to compare these results with other sources of denominator data. We developed a precise micro-plan using satellite imagery, and used the navigation tool EpiSample v1 in the field to guide teams to each building, without duplications or omissions. The particular characteristics of the selected ward underscore the importance of using standardized shape files to draw precise boundaries for enumeration micro-plans. While the use of this methodology did not resolve the discrepancy between independent and administrative vaccination coverage rates, a simplified application can better define the target population for routine immunization services and estimate the number of children still unprotected from vaccine-preventable diseases.

Float dust deposits in coal mine return airways pose a risk in the event of a methane ignition. Controlling airborne dust prior to deposition in the return would make current rock dusting practices more effective and reduce the risk of coal-dust-fueled explosions. The goal of this U.S. National Institute for Occupational Safety and Health study is to determine the potential of open-Air water sprays to reduce concentrations of airborne float coal dust, smaller than 75 microm in diameter, in longwall face airstreams. This study evaluated unconfined water sprays in a featureless tunnel ventilated at a typical longwall face velocity of 3.6 m/s (700 fpm). Experiments were conducted for two nozzle orientations and two water pressures for hollow cone, full cone, flat fan, air atomizing and hydraulic atomizing spray nozzles. Gravimetric samples show that airborne float dust removal efficiencies averaged 19.6 percent for all sprays under all conditions. The results indicate that the preferred spray nozzle should be operated at high fluid pressures to produce smaller droplets and move more air. These findings agree with past respirable dust control research, providing guidance on spray selection and spray array design in ongoing efforts to control airborne float dust over the entire longwall ventilated opening.

Float coal dust, generated by mining operations, is distributed throughout mine airways by ventilating air designed to purge gases and respirable dust. Float coal dust poses an explosion hazard in the event of a methane ignition. Current regulation requires the application of inert rock dust in areas subjected to float coal dust in order to mitigate the hazard. An alternate method using water sprays, which have been effective in controlling respirable dust hazards, has been proposed as a way to control float coal dust generated on longwall faces. However, the knockdown efficiency of the proposed water sprays on float coal dust needs to be verified. This study used gravimetric isokinetic Institute of Occupational Medicine (IOM) samplers alongside a real-time aerosol monitor (Cloud Aerosol Spectrometer with polarization; CAS-POL) to study the effects of spray type, operating pressure, and spray orientation on knockdown efficiencies for seven different water sprays. Because the CAS-POL has not been used to study mining dust, the CAS-POL measurements were validated with respect to the IOM samplers. This study found that the CAS-POL was able to resolve the same trends measured by the IOM samplers, while providing additional knockdown information for specific particle size ranges and locations in the test area. In addition, the CAS-POL data was not prone to the same process errors, which may occur due to the handling of the IOM filter media, and was able to provide a faster analysis of the data after testing. This study also determined that pressure was the leading design criteria influencing spray knockdown efficiency, with spray type also having some effect and orientation having little to no effect. The results of this study will be used to design future full-scale float coal dust capture tests involving multiple sprays, which will be evaluated using the CAS-POL.

Float coal dust is produced by various mining methods, carried by ventilating air and deposited on the floor, roof and ribs of mine airways. It deposited, float dust is re-entrained during a methane explosion. Without sufficient inert rock dust quantities, this float coal dust can propagate an explosion throughout mining entries. Consequently, controlling float coaf dust is of critical interest to mining operations. Rock dusting, which is the adding of inert material to airway surfaces, is the main control technique currently used by the coal mining industry to reduce the float coal dust explosion hazard. To assist the industry in reducing this hazard, the Pittsburgh Mining Research Division of the U.S. National Institute for Occupational Safety and Health initiated a project to investigate methods and technologies to reduce float ooal dust in underground coal mines through prevention, capture and suppression prior to deposition. Field characterization studies were performed to determine quantitatively the sources, types and amounts of dust produced during various coal mining processes. The operations chosen for study were a continuous miner section, a longwall section and a coal-handling facility. For each of these operations, the primary dust sources were confirmed to be the continuous mining machine, longwall shearer and conveyor belt transfer points, respectively. Respirable and total airborne float dust samples were collected and analyzed for each operation, and the ratio of total airborne float coal dust to respirable dust was calculated. During the continuous mining process, the ratio of total airborne float ooal dust to respirable dust ranged from 10.3 to 13.6. The ratios measured on the longwall face were between 1B.5 and 21.5. The total airborne float coal dust to respirable dust ratio observed during belt transport ranged between 7.5 and 21.8.

Coal dust produced during underground coalmining, i.e. float dust, which deposits throughout the coal mine can be feedstock for coal dust explosions. To prevent these explosions, inert rock dust (limestone dust) is applied to roof, floor, and ribs areas of a coal mine. The ratio of incombustible mass (rock dust + incombustible content of coal dust) divided by total mass of the deposited dust is defined as the Total Incombustible Content (TIC) of the deposited dust within the mine. Regulations require that a minimum TIC ratio (80%;) to be maintained for safe working conditions inside the mine. This paper presents design, fabrication and experimental results for a real-time sensing module which uses continuous optical and dielectrometry methods to measure the TIC of the deposited float dust/rock dust. The optical sensor determines the TIC of the deposited dust based on optical reflection which is described by modified Beer Law. We present an extension of the Bouguer-Beer-Lambert Law to find the relation between the reflectivity of a layer of known thickness (obtained by interdigital dielectrometry sensor) of a dust mixture to the ratio of each constituent. We also present the experimental results from testing the sensor prototypes in a realistic laboratory test bed that is subjected to the deposition of the coal dust/rock dust mixture. The sensor performance and stability at different humidity levels is evaluated and the accuracy of the results are compared to the currently established best practices for measuring TIC in underground coal mines.

During the poliovirus outbreak in Cameroon from October 2013 to April 2015, the Ministry of Public Health's Expanded Program on Immunization requested technical support to improve mapping of health district boundaries and health facility locations for more effective planning and analysis of polio program data. In December 2015, teams collected data on settlements, health facilities, and other features using smartphones. These data, combined with high-resolution satellite imagery, were used to create new health area and health district boundaries, providing the most accurate health sector administrative boundaries to date for Cameroon. The new maps are useful to and used by the polio program as well as other public health programs within Cameroon such as the District Health Information System and the Emergency Operations Center, demonstrating the value of the Global Polio Eradication Initiative's legacy.

BACKGROUND: Transmission of wild poliovirus (WPV) has never been interrupted in Afghanistan, Pakistan, and Nigeria. Since 2003, infections with WPV of Nigerian origin have been detected in 25 polio-free countries. In 2012, the Nigerian government created an emergency operations center and implemented a national emergency action plan to eradicate polio. The 2013 revision of this plan prioritized (1) improving the quality of supplemental immunization activities (SIAs), (2) implementing strategies to reach underserved populations, (3) adopting special approaches in security-compromised areas, (4) improving outbreak response, (5) enhancing routine immunization and activities implemented between SIAs, and (6) strengthening surveillance. This report summarizes implementation of these activities during a period of unprecedented insecurity and violence, including the killing of health workers and the onset of a state of emergency in the northeast zone. METHODS: This report reviews management strategies, innovations, trends in case counts, vaccination and social mobilization activities, and surveillance and monitoring data to assess progress in polio eradication in Nigeria. RESULTS: Nigeria has made significant improvements in the management of polio eradication initiative (pei) activities with marked improvement in the quality of SIAs, as measured by lot quality assurance sampling (LQAS). Comparing results from February 2012 with results from December 2013, the proportion of local government areas (LGAs) conducting LQAS in the 11 high-risk states at the ≥90% pass/fail threshold increased from 7% to 42%, and the proportion at the 80%-89% threshold increased from 9% to 30%. During January-December 2013, 53 polio cases were reported from 26 LGAs in 9 states in Nigeria, compared with 122 cases reported from 13 states in 2012. No cases of WPV type 3 infection have been reported since November 2012. In 2013, no polio cases due to any poliovirus type were detected in the northwest sanctuaries of Nigeria. In the second half of 2013, WPV transmission was restricted to Kano, Borno, Bauchi, and Taraba states. Despite considerable progress, 24 LGAs in 2012 and 7 LGAs in 2013 reported ≥2 cases, and WPV continued to circulate in 8 LGAs that had cases in 2012. Campaign activities were negatively impacted by insecurity and violence in Borno and Kano states. CONCLUSIONS: Efforts to interrupt transmission remain impeded by poor SIA implementation in localized areas, anti-polio vaccine sentiment, and limited access to vaccinate children because of insecurity. Sustained improvement in SIA quality, surveillance, and outbreak response and special strategies in security-compromised areas are needed to interrupt WPV transmission in 2014.

OBJECTIVE: To characterize work-related asthma by gender. METHODS: We analyzed state-based sentinel surveillance data on confirmed work-related asthma cases collected from California, Massachusetts, Michigan, and New Jersey during 1993-2008. We used Chi-square and Fisher's Exact Test statistics to compare select characteristics between females and males. RESULTS: Of the 8239 confirmed work-related asthma cases, 60% were female. When compared to males with work-related asthma, females with work-related asthma were more likely to be identified through workers' compensation (14.8% versus 10.6%) and less likely to be identified through hospital data (14.2% versus 16.9%). Moreover, when compared to males, females were more likely to have work-aggravated asthma (24.4% versus 13.5%) and less likely to have new-onset asthma (48.0% versus 56.5%). Females were also more likely than males with work-related asthma to work in healthcare and social assistance (28.7% versus 5.2%), educational services (11.8% versus 4.2%), and retail trade (5.0% versus 3.9%) industries and in office and administrative support (20.0% versus 4.0%), healthcare practitioners and technical (13.4% versus 1.6%), and education training and library (6.2% versus 1.3%) occupations. Agent groups most frequently associated with work-related asthma were miscellaneous chemicals (20.3%), cleaning materials (15.3%), and indoor air pollutants (14.9%) in females and miscellaneous chemicals (15.7%), mineral and inorganic dusts (13.2%), and pyrolysis products (12.7%) in males. CONCLUSIONS: Among adults with work-related asthma, males and females differ in terms of workplace exposures, occupations, and industries. Physicians should consider these gender differences when diagnosing and treating asthma in working adults.

Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available. copyright 2010 by the authors.