Assessing Photostability of mAb Formulations In Situ Using Light-Coupled NMR Spectroscopy.

Biopharmaceuticals, such as monoclonal antibodies (mAbs), need to maintain their chemical and physical stability in formulations throughout their lifecycle. It is known that exposure of mAbs to light, particularly UV, triggers chemical and physical degradation, which can be exacerbated by trace amounts of photosensitizers in the formulation. Although routine assessments of degradation following defined UV dosages are performed, there is a fundamental lack of understanding regarding the intermediates, transient reactive species, and radicals formed during illumination, as well as their lifetimes and immediate impact post-illumination. In this study, we used light-coupled NMR spectroscopy to monitor in situ live spectral changes in sealed samples during and after UV-A illumination of different formulations of four mAbs without added photosensitizers. We observed a complex evolution of spectra, reflecting the appearance within minutes of transient radicals during illumination and persisting for minutes to tens of minutes after the light was switched off. Both mAb and excipient signals were strongly affected by illumination, with some exhibiting fast irreversible photodegradation and others exhibiting partial recovery in the dark. These effects varied depending on the mAb and the presence of excipients, such as polysorbate 80 (PS80) and methionine. Complementary ex situ high-performance size-exclusion chromatography analysis of the same formulations post-UV exposure in the chamber revealed significant loss of purity, confirming formulation-dependent degradation. Both approaches suggested the presence of degradation processes initiated by light but continuing in the dark. Further studies on photoreaction intermediates and transient reactive species may help mitigate the impact of light on biopharmaceutical degradation.

Come for the Tobacco, Stay for the Flavor: Flavored Cigarillo-Use Trajectories Among Young Adult Sexual Gender Minority Women.

INTRODUCTION: The purpose of this research was to identify how young adult sexual gender minority (SGM) women who use cigarillos may respond to cigar flavor restrictions. AIMS AND METHODS: Young adults aged 21-28 years in the United States who currently use cigarillos were recruited between October 2020 and April 2021 to participate in an online survey. Due to high prevalence of cigarillo use among individuals who identify as sexual and/or gender minority (SGM) women, their (n = 192) flavored tobacco-use behaviors and anticipated responses to cigarillo flavor restrictions were compared to cisgender heterosexual (CisHet) women (n = 110). Logistic regression was used to model cigarillo cessation and product-switching behaviors (flavored and unflavored). RESULTS: SGM women were significantly less likely to report the use of flavor at the initiation of cigarillo use (61.7% vs. 86.1%) but were no different in current flavor use compared to CisHet women, with more than 80% of all women using any flavor. SGM women were 2.36 times as likely to say they would discontinue using cigarillos if flavors were unavailable. Among those who would continue using cigarillos, SGM women were 4.53 times as likely to endorse switching to an unflavored tobacco product but had the same likelihood of saying they would switch to flavored product compared to CisHet women. CONCLUSIONS: Flavor restriction policies may not reduce the initiation of cigarillos among SGM women and may elicit differential cigarillo use and tobacco product substitution by SGM identity. Flavor restriction policies should be coupled with targeted cessation resources to address potential remaining disparities. IMPLICATIONS: SGM US women have a unique cigarillo-use trajectory. These women are more likely to initiate cigarillos without flavor and then later integrate it into their behavior. National cigar flavor restrictions are expected to have a greater impact decreasing cigarillo initiation among CisHet women and decreasing current cigarillo use among SGM women. However, for those who would continue using unflavored cigarillos, SGM women may remain at risk for nicotine dependence due to increased product substitution. SGM women should be prioritized for cessation resources to reduce tobacco-use disparities leading up to and following the implementation of cigar flavor restrictions.

Influence of running on incidental and integral vitality and fatigue: An intensive longitudinal intervention in young Women's daily life.

Exercise intensity and perceived autonomy are important factors for the affective response toward exercise and adherence. Dual-mode theory suggests an inverted-J response curve of affect with increased exercise intensity, but little is known about how different running programs affect the affective response and subsequent incidental affect in daily life. This ambulatory assessment study examines the short- to long-term effects of two 8-week running interventions (affect-based vs. polarized-prescribed) on subjective vitality and perceived fatigue in young female novices. Participants engaged in 3 × 30 minute running sessions weekly in their natural environments and completed electronic diaries three times daily. Autoregressive multilevel models indicate small effects of training intensity on immediate affective subjective vitality (ß = -2.37; p = .03; f2 = 0.02) but negligible non-significant effects on fatigue (ß = 0.26; p = 0.12; f2 = 0.002). Novices experienced increased vitality throughout the day when their running was evaluated positively (ß = 0.23; p = .03; f2 = 0.04), with effects lasting over two days before returning to baseline (ß = -0.26; p < .001; f2 = 0.004). However, no significant long-term effects were observed over 8 weeks in vitality or fatigue. Results indicate between- and within-person variations, but limited sample power does not allow differentiating between programs. This study supports the dual-mode theory and highlights the importance of distinguishing affective response from incidental affect.

A Randomized Trial to Address Food Insecurity and Promote Smoking Cessation Among Low-Income Adults.

Many low-income adults who smoke also have unmet social needs, such as food insecurity, which can serve as a barrier to smoking cessation. We developed a novel intervention to jointly address smoking cessation and food insecurity and assessed its feasibility, acceptability, and preliminary outcomes. We enrolled participants who screened for food insecurity, reported smoking daily, and were ready to quit. All participants received 3 months of resources navigation from a community health worker through monthly telephone calls for referrals and check-ins for smoking cessation and food access resources. Participants randomized to the intervention group received an economic intervention equivalent to the cost of 1 week of groceries/month for 3 months. We randomized 55 participants who were smoking on average 13 cigarettes/day. The trial was feasible and acceptable based on 3-month retention rates (80%) and end-of-study qualitative feedback (91% would recommend the study to others). At 3 months, participants in the intervention versus control group reported a longer length of abstinence from smoking and had a higher proportion of serious quit attempts. Results from this pilot study suggest the importance of attending to social needs, particularly food insecurity, as a strategy to promote smoking cessation among low-income adults who smoke.

The perspective of school leaders on the implementation of evidence-based practices: A mixed methods study.

Background: School leaders play an integral role in the use of implementation strategies, which in turn support special education teachers in the implementation of evidence-based practices (EBPs). In this convergent mixed methods study, we explored school leaders' perceptions of the facilitators and barriers to EBP implementation, particularly for students receiving special education, as well as the importance and feasibility of 15 implementation strategies. Method: School leaders (N = 22, principals, assistant principals, school psychologists, etc.) participated in a semistructured interview that included three parts-qualitative questions, quantitative ratings of strategies' importance and feasibility, and discussion of the top three implementation strategies. Data strands were analyzed independently and then integrated to generate meta-inferences. Results: The qualitative data identified facilitators such as access to resources about the intervention (e.g., professional development) and collaboration and teamwork, while barriers centered on lack of school supports, culture/climate, and organizational factors (e.g., lack of communication). The quantitative data indicated that the implementation strategy provide ongoing consultation/coaching was rated as important and feasible. Monitor the progress of the implementation effort was rated as important but less feasible, while conduct educational meetings and change the environment were rated as feasible, but less important. Build partnerships to support implementation was rated as less important and feasible. There was convergence and divergence in mixed methods findings. Conclusion: This study underscores the critical need to increase school leaders' knowledge and skills related to implementation science to better leverage implementation strategies that address the confluence of relevant implementation determinants.

School leaders, such as principals, assistant principals, and school psychologists, are responsible for supporting special education teachers in doing interventions (e.g., through teacher training). In this study, we interviewed 22 school leaders to understand what factors support or hinder teachers in doing interventions, especially for students receiving special education. We also provided school leaders with a list of 15 strategies that may be used to support teachers, to determine which strategies school leaders think are the most important and feasible in schools. Our results indicated that it is important to train school leaders on how to move research into practice settings, such as schools. It is equally important for researchers and policymakers to understand the priorities of school leaders.

Longitudinal experience of food insecurity & cigarette use in the early COVID-19 Pandemic, United States.

Food insecurity is associated with cigarette smoking, yet little is known about how variability in the experience of food insecurity may relate to patterns of cigarette use. We sought to examine patterns of food insecurity and cigarette use during the COVID-19 pandemic (April 2020-March 2021). We analyzed longitudinal survey data from a nationally representative panel of adults in the United States (N = 7,880) from the Understanding Coronavirus in America Study. The primary independent variable was ten trajectories of food insecurity. Our dependent variable was past 7-day cigarette use (count of days used cigarettes). Poisson regression using generalized estimating equations was run controlling for key covariates. The prevalence of cigarette use on at least one day in the past week was lowest (17.5 %) for those who Remained Food Secure, and highest (57.9 %) among those who Became Fully Food Insecure, a group characterized by having high probability of becoming food insecure during the study period. Among those who reported at least one day of cigarette use in the past week, fewer than half (40.1 %) reported sustained use across all waves of the study. Those who Became Fully Food Insecure had an incidence rate ratio (IRR) of 1.73 (95 % CI: 1.18, 2.54) compared to those who Remained Food Secure with respect to number of smoking days. While different patterns of food insecurity are related to cigarette smoking at the population level, these results highlight that food insecurity, a key social need, may represent a novel strategy for informing reduction of tobacco use disparities.

What is (Un)Flavored? A Scoping Review of the Conceptualization of Flavored Cigarillos.

PURPOSE: To identify how flavor is conceptualized with respect to cigarillos to illuminate areas of concordance and discordance and provide a pathway for the harmonization of tobacco flavor measurement. METHODS: Three methods were used to identify research measuring flavors respective to cigarillo products including: 1) querying research databases using key words 'cigarillo,' 'tobacco' and 'flavor'/'flavour,' 2) sub-sampling of the eligible literature with backwards and forwards reference searching, and 3) a bibliographic search of key experts. Two reviewers independently screened titles, abstracts, and full texts. Inclusion criteria required manuscripts to be available in English, published prior to 3/1/2022, be original and peer-reviewed, and include a measure of flavor pertaining to cigarillo products. A total of 163 manuscripts met these criteria and were subsequently evaluated. RESULTS: Cigarillo flavor determinations were made based on the presence of flavoring agents, sensory characteristics, marketing or package characteristics, pre-defined lists, the absence of any of these, and/or were undefined. Individual flavors and their related classifications were not altogether mutually exclusive due to differences in conceptualization which has evolved over time. CONCLUSION: Flavor measures continue to evolve, likely in response to both tobacco control policies and industry shifts. There is a lack of standardization in flavor conceptualization that can be ameliorated through intentional integration of multiple forms of research such as identifying patterns of flavoring agents and/or marketing strategies that elicit a specific flavor profile. By doing this, we may more comprehensively evaluate the impact of flavors, their constituents, and related marketing strategies on broader population health. IMPLICATIONS: There are discrepancies in the conceptualization of flavor in tobacco and nicotine products. The lack of standardized, definitive language limits our ability to comprehensively evaluate the population-level health impact of flavors in addition to our ability to effectively inform, implement and enforce policies restricting flavors in tobacco and nicotine products.

Core Components and Implementation Determinants of Multilevel Service Delivery Frameworks Across Child Mental Health Service Settings.

Multilevel service delivery frameworks are approaches to structuring and organizing a spectrum of evidence-based services and supports, focused on assessment, prevention, and intervention designed for the local context. Exemplar frameworks in child mental health include positive behavioral interventions and supports in education, collaborative care in primary care, and systems of care in community mental health settings. Yet, their high-quality implementation has lagged. This work proposes a conceptual foundation for multilevel service delivery frameworks spanning diverse mental health service settings that can inform development of strategic implementation supports. We draw upon the existing literature for three exemplar multilevel service delivery frameworks in different child mental health service settings to (1) identify core components common to each framework, and (2) to highlight prominent implementation determinants that interface with each core component. Six interrelated components of multilevel service delivery frameworks were identified, including, (1) a systems-level approach, (2) data-driven problem solving and decision-making, (3) multiple levels of service intensity using evidence-based practices, (4) cross-linking service sectors, (5) multiple providers working together, including in teams, and (6) built-in implementation strategies that facilitate delivery of the overall model. Implementation determinants that interface with core components were identified at each contextual level. The conceptual foundation provided in this paper has the potential to facilitate cross-sector knowledge sharing, promote generalization across service settings, and provide direction for researchers, system leaders, and implementation intermediaries/practitioners working to strategically support the high-quality implementation of these frameworks.

Does prey availability influence the detection of Dinophysis spp. by the imaging FlowCytobot?

The Imaging FlowCytobot (IFCB) is a field-deployable imaging-in-flow cytometer that is increasingly being used to monitor harmful algae. The IFCB acquires images of suspended particles based on their chlorophyll-a fluorescence and/or the amount of light they scatter (side scattering). The present study hypothesized that fluorescence-based image acquisition would undercount Dinophysis spp., a genus of non-constitutive mixotrophs, when prey is limited. This is because Dinophysis spp. acquire plastids via ingestion of their ciliate prey Mesodinium spp., and lose photosynthetic capacity and autofluorescence in the absence of prey. Even small blooms of Dinophysis spp. can be highly toxic and result in diarrhetic shellfish poisoning (DSP), highlighting the importance of accurately detecting low abundances. To explore this, laboratory experiments were conducted to determine optimal IFCB settings for a fed culture of Dinophysis acuminata, and an existing time series of IFCB observations collected in Puget Sound (Washington, U.S.A) was used to compare Dinophysis spp. abundance estimates from samples triggered via side scattering versus fluorescence in relation to Mesodinium spp. abundance. This study introduces a quantitative approach for optimizing the detection of target harmful algae which can be repeated across multiple IFCBs and demonstrates the effects of IFCB calibration on Dinophysis spp. detection. The laboratory experiments showed that IFCB settings for fluorescence-based image acquisition need to be fairly sensitive to accurately detect D. acuminata cells. A poorly calibrated IFCB can miss a significant proportion of D. acuminata abundance whatever the method used to trigger the image acquisition. Field results demonstrated that the physiological status of Dinophysis spp. can influence their detection by the IFCB when triggering on fluorescence. This was observed during a 7-day period when the IFCB failed to detect Dinophysis spp. cells when triggering on fluorescence while cells were still detected using the side scattering triggering method as well as observed by microscopy. During this period, Mesodinium spp. was not detected, IFCB-derived autofluorescence level of individual cells of Dinophysis spp. was low, and less than 50 % of Dinophysis spp. cells exhibited autofluorescence under the microscope. Together, this indicates that the unique feeding ecology of Dinophysis spp. may affect their detection by the IFCB when cells are starved.

Recency measures matter: Variability in reported last use of tobacco and marijuana products among a nationally representative study of U.S. young adults.

INTRODUCTION: Current use of tobacco and marijuana products is largely defined as use within the past 30-days or more recently. These products are not used in the same manner, frequency, or context especially among young adults who are increasingly at risk for poly-product use. The purpose of this study was to examine patterns of most recent product use across select tobacco and marijuana products. MATERIALS AND METHODS: Data used in this study come from a cross-sectional survey conducted among a nationally representative sample of young adults ages 18-34 (n = 1,189) in the U.S. from October-November 2020. Respondents were asked about past product and most recent use of select tobacco/nicotine products (cigarettes, little filtered cigars and cigarillos, large cigars, e-cigarettes, hookah/water pipes) and marijuana products (blunts, e-cigarettes with marijuana, and other products with marijuana). RESULTS: A high proportion of young adults reported having used at least one tobacco (79.6%) or marijuana (68.6%) products. There is variability in the distribution of most recent use across different tobacco and marijuana users even within the past 3 to past 6 months where nearly one in five users of any product report last use. The average number of tobacco/nicotine products used as well as concurrent marijuana use were lowest when looking at those whose most recent use was within the past 30-days. As the measures of most recent use became more broad, the number of tobacco/nicotine products used increased as did the prevalence of concurrent marijuana use which extended through the past 6-months. CONCLUSION: Measures of current use may need to be expanded beyond the past 30-days to include through the past 6-months to better encapsulate usage patterns when considering poly-tobacco and marijuana co-use.

A survey of Dinophysis spp. and their potential to cause diarrhetic shellfish poisoning in coastal waters of the United States.

Multiple species of the genus Dinophysis produce diarrhetic shellfish toxins (okadaic acid and Dinophysis toxins, OA/DTXs analogs) and/or pectenotoxins (PTXs). Only since 2008 have DSP events (illnesses and/or shellfish harvesting closures) become recognized as a threat to human health in the United States. This study characterized 20 strains representing five species of Dinophysis spp. isolated from three US coastal regions that have experienced DSP events: the Northeast/Mid-Atlantic, the Gulf of Mexico, and the Pacific Northwest. Using a combination of morphometric and DNA-based evidence, seven Northeast/Mid-Atlantic isolates and four Pacific Northwest isolates were classified as D. acuminata, a total of four isolates from two coasts were classified as D. norvegica, two isolates from the Pacific Northwest coast were identified as D. fortii, and three isolates from the Gulf of Mexico were identified as D. ovum and D. caudata. Toxin profiles of D. acuminata and D. norvegica varied by their geographical origin within the United States. Cross-regional comparison of toxin profiles was not possible with the other three species; however, within each region, distinct species-conserved profiles for isolates of D. fortii, D. ovum, and D. caudata were observed. Historical and recent data from various State and Tribal monitoring programs were compiled and compared, including maximum recorded cell abundances of Dinophysis spp., maximum concentrations of OA/DTXs recorded in commercial shellfish species, and durations of harvesting closures, to provide perspective regarding potential for DSP impacts to regional public health and shellfish industry.

A roadmap to equitable school mental health screening.

Youth in the United States are experiencing mental health concerns at alarming rates. Considering the nation's legacy of racism and growing recognition of the impact of social determinants of health on educational and mental health inequities, it is imperative to re-envision how we approach mental health screening in schools to center equity. A focus on mental health screening for the sole purpose of identifying individual at-risk students ignores key contextual considerations, is ineffective in addressing health and educational inequities, and has the potential to perpetuate oppressive practices in schools. Equity-focused mental health screening requires a shift from individual- and deficit-focused approaches to systems- and holistic-focused approaches that (a) identify strengths and stressors among individuals, groups, and communities; (b) dismantle structural forms of oppression; and (c) promote positive mental health outcomes for minoritized youth. Integrating recommendations from the educational equity literature and critical school mental health frameworks, this paper identifies core considerations for equitable school mental health screening and provides guiding principles for each phase of the screening process, from screening readiness to execution to follow up. To implement these recommendations and transform school-based mental health care, schools should (a) incorporate multiple perspectives; (b) prioritize student, family, and community voices; and (c) build collaborative partnerships to co-construct a vision for equitable school mental health.

Food Insecurity Trajectories in the US During the First Year of the COVID-19 Pandemic.

INTRODUCTION: The objective of this study was to characterize population-level trajectories in the probability of food insecurity in the US during the first year of the COVID-19 pandemic and to examine sociodemographic correlates associated with identified trajectories. METHODS: We analyzed data from the Understanding America Study survey, a nationally representative panel (N = 7,944) that assessed food insecurity every 2 weeks from April 1, 2020, through March 16, 2021. We used latent class growth analysis to determine patterns (or classes) of pandemic-related food insecurity during a 1-year period. RESULTS: We found 10 classes of trajectories of food insecurity, including 1 class of consistent food security (64.7%), 1 class of consistent food insecurity (3.4%), 5 classes of decreasing food insecurity (15.8%), 2 classes of increasing food insecurity (4.6%), and 1 class of stable but elevated food insecurity (11.6%). Relative to the class that remained food secure, other classes were younger, had a greater proportion of women, and tended to identify with a racial or ethnic minority group. CONCLUSION: We found heterogeneous longitudinal patterns in the development, resolution, or persistence of food insecurity during the first year of the COVID-19 pandemic. Experiences of food insecurity were highly variable across the US population, with one-third experiencing some form of food insecurity risk. Findings have implications for identifying population groups who are at increased risk of food insecurity and related health disparities beyond the first year of the pandemic.

Characterization of a Novel Particle in a Pharmaceutical Drug Product.

A previously unreported particle type was observed during routine visual vial inspection of a liquid drug product and suspected to be the result of vial delamination. Delamination is the corrosive attack on the interior surface of a glass container resulting in the release of thin flake-like glass particles, lamellae, into solution. It is a major concern for pharmaceutical companies, especially for parenteral solutions, and drug programs with a high risk for delamination are typically monitored for lamellae formation through long-term stability studies. Although these particles observed resembled lamellae (i.e., thin, reflecting light, buoyant) they were not the result of glass delamination. In this study, the authors describe a previously unreported particle type and provide a detailed comparison with known lamellae exposed to the same drug formulation. The chemical, elemental, and morphological characteristics of the particles and respective vials are described in detail. Overall, the particles' high organic and low silica elemental signature, along with no signs of delamination on the glass vial inner surface demonstrate that this lamellae-like observation is a novel particle form that can be distinguished from lamellae formed from vial glass delamination.

Development and Qualification of Visible Particle Load Analysis Methods for Injectable Drug Product Primary Packaging Components.

In the biopharmaceutical industry, the observation of a single particle in a vial or syringe may result in entire lots of drug product recalls. U.S. Pharmacopeia <787> and <788> describe light obscuration methods and particle collection (membrane filtration) followed by light microscopy for particle counting of filled drug products. However, there are no corresponding pharmacopeial methods for determining the particle levels of unfilled primary packaging components or their packaging materials (tubs, nests, bags, etc.). This article describes a quantification method to accurately assess the number of particles in primary containers and corresponding closures. As a microscopic method, the size ranges can be set by the user and are limited only by the optical properties of the microscope and analysis time. Particle load is a critical quality attribute that has a direct impact on product safety. Applying a standardized method to compare the effect of process changes on particle load can aid manufacturers in refining their processes to minimize particulates. Described herein are the critical parameters to develop physical rinse methods and the subsequent qualification results to measure the visible particle load of nonsiliconized and siliconized primary packaging systems.

Comparing Informants for Mental Health Screening at the Preschool Level.

Universal screening for mental health in preschools provides the opportunity for early identification and early intervention, but guidance regarding which informants to use is needed. Preschoolers' (N = 535) parent and teacher reports across two screening forms were analyzed to determine similarities and discrepancies for classification results and screener scores. The analyses also examined if an additional rater provided incrementally valid information to the prediction of longitudinal kindergarten outcomes. Parents' and teachers' screening scores were significantly correlated across forms by rater and across raters. However, categorical classification results indicated that teachers were more likely than parents to rate preschoolers in at-risk ranges across forms. Finally, hierarchical regression analyses revealed teacher ratings were predictive of kindergarten social-emotional, cognitive, and academic outcomes, and that the addition of parent ratings did not significantly improve prediction of outcomes. Implications are discussed in the context of multiple raters within multiple-gating screening procedures.

Flavour loyalty may predict cessation or substitution following a cigarillo flavour ban among young adults in the USA.

SIGNIFICANCE: The purpose of this research was to measure flavour loyalty and identify how current cigarillo users may respond to a hypothetical flavour ban in the USA. METHODS: Cigarillo users aged 21-28 (n=531) were recruited between October 2020 and April 2021 to participate in an online survey. Respondents categorised their preferred, usual and current cigarillo flavours. Individuals who preferred tobacco flavours were compared with individuals who preferred any other flavours. Strength of preferences, or flavour loyalty, was defined when an individual's preferred flavour matched what they use both usually and currently creating a spectrum of individuals with a strong tobacco preference (n=34), weak tobacco preference (n=20), weak flavour preference (n=162) and strong flavour preference (n=315). Those preferring tobacco were aggregated into any tobacco preference (n=54). RESULTS: Individuals who preferred any flavour scored higher on a scale of nicotine dependence. There was a dose-response relationship in those who said they would discontinue cigarillos if flavoured options were not available: 11.4% of individuals with any tobacco flavour preference, 27.8% of those with a weak flavour preference and 38.1% of those with a strong flavour preference. A similar trend was noted among those who would switch to another product: 19.2% of those with tobacco flavour preference, 34.3% of those with a weak flavour preference and 43.2% of those with a strong flavour preference. CONCLUSION: Individuals who display strong flavour preferences were more likely to say they would discontinue use or seek out alternative flavoured products following a ban on flavoured cigarillos.

Tobacco Whack-A-Mole: A Consumption Taxonomy of Cigar & Other Combustible Tobacco Products among a Nationally Representative Sample of Young Adults.

INTRODUCTION: Little filtered cigars and cigarillos (LCCs) are consumed infrequently, co-administered with marijuana, and concurrently used with other tobacco products. Reliance on the past 30-day use estimate, a marker of tobacco user status, may underestimate the dynamic nature of intermittent LCC and other tobacco product use. We developed a framework to capture the intermittent nature of exclusive LCC use and dual/poly use with cigarettes and large cigars using broader timing of last product use categories and product use modality (e.g., with marijuana). METHODS: Data come from the baseline C'RILLOS study, a U.S. nationally representative sample of young adults aged 18-34 (n = 1063) collected in October 2019. We developed a consumption taxonomy framework that accounted for respondents' modality of LCC use (i.e., use with tobacco, LCC-T, or use with marijuana as blunts, LCC-B), the exclusive use of LCCs and other tobacco products (i.e., cigarettes, and large cigars) or their co-use and the timing of last product use (i.e., ever and past 30 days, past 3 months, past 6 months, greater than 6 months). RESULTS: Seventy-five percent of our sample reported ever use of any combustible tobacco product, including LCCs. The most common ever use pattern was poly use of LCC-T + LCC-B + cigarettes (16%). Our consumption taxonomy framework demonstrated the fluid nature of combustible tobacco product use among LCC users. For instance, among past 30-day cigarette users, 48% reported using LCC-T, 39% reported using LCC-B, and 32% reported using large cigars in the past 3 months or more. DISCUSSION: The tobacco use field currently classifies 'tobacco users' based on the product they smoked in the past 30 days. Any tobacco product use beyond the past 30-day period is considered 'discontinued use' and not the focus of intervention or tobacco regulatory science decisions. We documented the substantial proportion of young adult LCC, cigarette, and large cigar users who either exclusively or dual/poly used these combustible products in recent (e.g., past 3 months) periods. To prevent underestimation of use, surveillance measures should assess the use modality, timing of last product use, and exclusive/multiple product use to more accurately identify the smoking status of young adult LCC users.

State-of-the-art and emerging trends in analytical approaches to pharmaceutical-product commercialization.

The biopharmaceutical landscape continues to evolve rapidly, and associated modality complexity and the need to improve molecular understanding require concomitant advances in analytical approaches used to characterize and release the product. The Product Quality Attribute Assessment (PQAA) and Quality Target Product Profile (QTPP) frameworks help catalog and translate molecular understanding to process and product-design targets, thereby enabling reliable manufacturing of high-quality product. The analytical target profile forms the basis of identifying best-fit analytical methods for attribute measurement and continues to be successfully used to develop robust analytical methods for detailed product characterization as well as release and stability testing. Despite maturity across multiple testing platforms, advances continue to be made, several with the potential to alter testing paradigms. There is an increasing role for mass spectrometry beyond product characterization and into routine release testing as seen by the progress in multi-attribute methods and technologies, applications to aggregate measurement, the development of capillary zone electrophoresis (CZE) coupled with mass spectrometry (MS) and capillary isoelectric focusing (CIEF) with MS for measurement of glycans and charged species, respectively, and increased application to host cell protein measurement. Multitarget engaging multispecific modalities will drive advances in bioassay platforms and recent advances both in 1- and 2-D NMR approaches could make it the method of choice for characterizing higher-order structures. Additionally, rigorous understanding of raw material and container attributes is necessary to complement product understanding, and these collectively can enable robust supply of high-quality product to patients.