Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants.

Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain (RBD) of the virus has challenged their efficacy. In particular, the emerging variants B.1.1.7, B.1.351 and P.1 (first detected in the UK, South Africa and Brazil, respectively) have compromised the efficacy of sera from patients who have recovered from COVID-19 and immunotherapies that have received emergency use authorization1-3. One potential alternative to avert viral escape is the use of camelid VHHs (variable heavy chain domains of heavy chain antibody (also known as nanobodies)), which can recognize epitopes that are often inaccessible to conventional antibodies4. Here, we isolate anti-RBD nanobodies from llamas and from mice that we engineered to produce VHHs cloned from alpacas, dromedaries and Bactrian camels. We identified two groups of highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region that is highly conserved in coronaviruses but rarely targeted by human antibodies. Group 2 is almost exclusively focused to the RBD-ACE2 interface and does not neutralize SARS-CoV-2 variants that carry E484K or N501Y substitutions. However, nanobodies in group 2 retain full neutralization activity against these variants when expressed as homotrimers, and-to our knowledge-rival the most potent antibodies against SARS-CoV-2 that have been produced to date. These findings suggest that multivalent nanobodies overcome SARS-CoV-2 mutations through two separate mechanisms: enhanced avidity for the ACE2-binding domain and recognition of conserved epitopes that are largely inaccessible to human antibodies. Therefore, although new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised.

Respiratory disease in rhesus macaques inoculated with SARS-CoV-2.

An outbreak of coronavirus disease 2019 (COVID-19), which is caused by a novel coronavirus (named SARS-CoV-2) and has a case fatality rate of approximately 2%, started in Wuhan (China) in December 20191,2. Following an unprecedented global spread3, the World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although data on COVID-19 in humans are emerging at a steady pace, some aspects of the pathogenesis of SARS-CoV-2 can be studied in detail only in animal models, in which repeated sampling and tissue collection is possible. Here we show that SARS-CoV-2 causes a respiratory disease in rhesus macaques that lasts between 8 and 16 days. Pulmonary infiltrates, which are a hallmark of COVID-19 in humans, were visible in lung radiographs. We detected high viral loads in swabs from the nose and throat of all of the macaques, as well as in bronchoalveolar lavages; in one macaque, we observed prolonged rectal shedding. Together, the rhesus macaque recapitulates the moderate disease that has been observed in the majority of human cases of COVID-19. The establishment of the rhesus macaque as a model of COVID-19 will increase our understanding of the pathogenesis of this disease, and aid in the development and testing of medical countermeasures.

Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2.

Effective therapies to treat coronavirus disease 2019 (COVID-19) are urgently needed. While many investigational, approved, and repurposed drugs have been suggested as potential treatments, preclinical data from animal models can guide the search for effective treatments by ruling out those that lack efficacy in vivo. Remdesivir (GS-5734) is a nucleotide analogue prodrug with broad antiviral activity1,2 that is currently being investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir was effective against infection with Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV)2,5,6. In vitro, remdesivir inhibited replication of SARS-CoV-27,8. Here we investigate the efficacy of remdesivir in a rhesus macaque model of SARS-CoV-2 infection9. Unlike vehicle-treated animals, macaques treated with remdesivir did not show signs of respiratory disease; they also showed reduced pulmonary infiltrates on radiographs and reduced virus titres in bronchoalveolar lavages twelve hours after the first dose. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, remdesivir-treated animals had lower lung viral loads and reduced lung damage. Thus, treatment with remdesivir initiated early during infection had a clinical benefit in rhesus macaques infected with SARS-CoV-2. Although the rhesus macaque model does not represent the severe disease observed in some patients with COVID-19, our data support the early initiation of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.

Two structurally defined Aß polymorphs promote different pathological changes in susceptible mice.

Misfolded Aß is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aß strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, tropism to specific brain regions, differential recruitment of Aß40 /Aß42 peptides, and induction of microglial and astroglial responses. Importantly, the aggregates induced by 2F and 3F are structurally different as determined by ssNMR. Our study analyzes the biological properties of purified Aß polymorphs that have been characterized at the atomic resolution level and provides relevant information on the pathological significance of misfolded Aß strains.

Social norms and dishonesty across societies.

Social norms have long been recognized as an important factor in curtailing antisocial behavior, and stricter prosocial norms are commonly associated with increased prosocial behavior. In this study, we provide evidence that very strict prosocial norms can have a perverse negative relationship with prosocial behavior. In laboratory experiments conducted in 10 countries across 5 continents, we measured the level of honest behavior and elicited injunctive norms of honesty. We find that individuals who hold very strict norms (i.e., those who perceive a small lie to be as socially unacceptable as a large lie) are more likely to lie to the maximal extent possible. This finding is consistent with a simple behavioral rationale. If the perceived norm does not differentiate between the severity of a lie, lying to the full extent is optimal for a norm violator since it maximizes the financial gain, while the perceived costs of the norm violation are unchanged. We show that the relation between very strict prosocial norms and high levels of rule violations generalizes to civic norms related to common moral dilemmas, such as tax evasion, cheating on government benefits, and fare dodging on public transportation. Those with very strict attitudes toward civic norms are more likely to lie to the maximal extent possible. A similar relation holds across countries. Countries with a larger fraction of people with very strict attitudes toward civic norms have a higher society-level prevalence of rule violations.

A bivalent Adenovirus-Vectored Vaccine induces a robust humoral response, but does not protect cynomolgus macaques against a lethal challenge with Sudan virus.

The most recent Sudan virus (SUDV) outbreak in Uganda was first detected in September 2022 and resulted in 164 laboratory-confirmed cases and 77 deaths. There are no approved vaccines against SUDV. Here, we investigated the protective efficacy of ChAdOx1-biEBOV in cynomolgus macaques using a prime or a prime-boost regimen. ChAdOx1-biEBOV is a replication-deficient simian adenovirus vector encoding SUDV and Ebola virus (EBOV) glycoproteins (GPs). Intramuscular vaccination induced SUDV and EBOV GP-specific IgG responses and neutralizing antibodies. Upon challenge with SUDV, vaccinated animals showed signs of disease like those observed in control animals, and no difference in survival outcomes were measured among all three groups. Viral load in blood samples and in tissue samples obtained after necropsy were not significantly different between groups. Overall, this study highlights the importance of evaluating vaccines in multiple animal models and demonstrates the importance of understanding protective efficacy in both animal models and human hosts.

The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters.

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel SARS-CoV-2 variant designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and it was shown to have enhanced infectivity in vitro and decreased antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both variants exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most marked body weight loss among the 3 variants. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three variants. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the oropharynx but not in the lungs. In multi-virus in-vivo competition experiments, we found that B.1. (614G), epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the nasal cavity, B.1. (614G), gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) and WA-1 variants in hamsters. These results demonstrate enhanced virulence and high relative oropharyngeal replication of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) variant.

Examining the predictive utility of behavioral economic demand indices and subjective effects on the actualized reinforcing value of menthol cigarettes and potential alternatives.

INTRODUCTION: Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs. METHODS: Eighty participants who typically smoked menthol cigarettes completed this clinical lab study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following one-week of substituting their preferred MCA for their UBMC, participants completed a 90-min concurrent-choice self-administration task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the lab with subsequent response effort for UBMCs on the concurrent-choice task. RESULTS: Three demand indices for UBMC were positively associated with UBMC response effort: Essential Value (EV; p=.02), Omax (p=.02), and breakpoint (p=.04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p=.03), Pmax (p=.04), Omax (p=.03), and breakpoint (p=.03). Subjective effects captured by the mCEQ were not associated with response effort. CONCLUSIONS: Demand indices reflecting Persistence (i.e., sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (i.e., addiction potential) of combustible tobacco products similar to the longer self-administration task. IMPLICATIONS: In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of cigarette purchase task efficiently capture information on the relative reinforcing value of usual brand menthol cigarettes and plausible alternative tobacco products, similar to a 90-min in-laboratory self-administration task.

The Moral Machine experiment.

With the rapid development of artificial intelligence have come concerns about how machines will make moral decisions, and the major challenge of quantifying societal expectations about the ethical principles that should guide machine behaviour. To address this challenge, we deployed the Moral Machine, an online experimental platform designed to explore the moral dilemmas faced by autonomous vehicles. This platform gathered 40 million decisions in ten languages from millions of people in 233 countries and territories. Here we describe the results of this experiment. First, we summarize global moral preferences. Second, we document individual variations in preferences, based on respondents' demographics. Third, we report cross-cultural ethical variation, and uncover three major clusters of countries. Fourth, we show that these differences correlate with modern institutions and deep cultural traits. We discuss how these preferences can contribute to developing global, socially acceptable principles for machine ethics. All data used in this article are publicly available.

Stability of Monkeypox Virus in Body Fluids and Wastewater.

An outbreak of human mpox infection in nonendemic countries appears to have been driven largely by transmission through body fluids or skin-to-skin contact during sexual activity. We evaluated the stability of monkeypox virus (MPXV) in different environments and specific body fluids and tested the effectiveness of decontamination methodologies. MPXV decayed faster at higher temperatures, and rates varied considerably depending on the medium in which virus was suspended, both in solution and on surfaces. More proteinaceous fluids supported greater persistence. Chlorination was an effective decontamination technique, but only at higher concentrations. Wastewater was more difficult to decontaminate than plain deionized water; testing for infectious MPXV could be a helpful addition to PCR-based wastewater surveillance when high levels of viral DNA are detected. Our findings suggest that, because virus stability is sufficient to support environmental MPXV transmission in healthcare settings, exposure and dose-response will be limiting factors for those transmission routes.

K18-hACE2 mice develop respiratory disease resembling severe COVID-19.

SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 102 TCID50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.

Substitutability of menthol cigarette alternatives: a clinical trial.

INTRODUCTION: This study assessed the substitutability of plausible combustible menthol cigarette alternatives (MCAs) for usual brand menthol cigarettes (UBMCs) in adults who smoke menthol cigarettes. METHODS: Following three in-lab sampling sessions, 80 adults aged 21-50 who smoke menthol cigarettes chose their preferred MCA: (1) a menthol roll-your-own cigarette (mRYO), (2) a menthol filtered little cigar (mFLC) or (3) a non-menthol cigarette (NMC). Participants were instructed to completely substitute their preferred MCA for their UBMC for 1 week and complete daily diaries documenting adherence and subjective effects. At the final lab visit, participants completed concurrent choice and cross-price elasticity tasks with their substitute product and UBMC as the comparator. RESULTS: Most (65%) participants chose mRYO as their preferred product, followed by NMC and mFLC. Adherence to MCA was high for all products across the week (range: 63%-88%). Positive subjective effects for mRYO decreased over time but remained numerically higher than the other MCA products; craving reduction also decreased for NMC across phases. In the progressive ratio task, participants chose their UBMC in 61.7% of choices; this did not differ by preferred MCA, although the median breakpoint was highest for mRYO and similar for mFLC and NMC. Cross-price elasticity comparing UBMC and the preferred product indicated high substitutability of each MCA at phase 3 (I values -0.70 to -0.82). CONCLUSIONS AND RELEVANCE: mRYOs were the most preferred MCA among the study products, but all MCAs were acceptable substitutes for UBMC using behavioural and economic measures in a short-term trial period.Trial registration number NCT04844762.

Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer.

OBJECTIVE: Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described. DESIGN: We performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and H3K9me3 for heterochromatin. RESULTS: We demonstrate that H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumour-specific enhancers for crucial oncogenes, such as ASCL2 and FZD10, was required for excessive proliferation. Consistently, combination of MEK plus bromodomain inhibition was found to have synergistic effects in CRC patient-derived xenograft models. Probing intertumour heterogeneity, we identified four distinct enhancer subtypes (EPIgenome-based Classification, EpiC), three of which correlate well with previously defined transcriptomic subtypes (consensus molecular subtypes, CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, TGFßi, mTORi and SRCi) for EpiC groups. CONCLUSION: Our data suggest that the dynamics of active enhancer underlies CRC progression and the patient-specific enhancer patterns can be leveraged for precision combination therapy.

Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes, Australia.

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.

Tailored text message and web intervention for smoking cessation in U.S. socioeconomically-disadvantaged young adults: A randomized controlled trial.

The prevalence of cigarette smoking in young adults is higher among those with socioeconomic disadvantage than those without. Low treatment-seeking among young adult smokers is compounded by few efficacious smoking cessation interventions for this group, particularly socioeconomically-disadvantaged young adults (SDYA) who smoke cigarettes. The goal of this study was to test a tailored smoking-cessation intervention for SDYA. 343 SDYA aged 18-30 living in the U.S. (85% female) who smoke cigarettes with access to a smartphone and interest in quitting smoking in the next six months were recruited online in Spring 2020 and randomized to referral to online quit resources (usual care control; n = 171) or a 12-week tailored text message smoking-cessation program with a companion web-based intervention (n = 172). Intent to treat analyses examined associations between study condition, self-reported 30-day point prevalence abstinence (PPA), and confidence to quit smoking at 12 weeks, controlling for potential confounders. Intervention group participants had greater self-reported 30-day PPA at 12-weeks than controls (adjusted relative risk 3.93, 95% CI 2.14-7.24). Among those who continued smoking, the intervention increased confidence to quit (0.81 points, 95% confidence interval 0.08-1.53). Weekly engagement in the intervention predicted greater cessation. A tailored text message intervention for SDYA increased smoking abstinence and confidence to quit at the end-of-treatment. Findings may have been influenced by recruitment at the start of the COVID pandemic but suggest that text messaging is an acceptable and efficacious cessation strategy for SDYA smokers. Future studies should examine the impact on longer-term smoking-cessation and importance of intervention tailoring for SDYA.

Intrinsic honesty and the prevalence of rule violations across societies.

Deception is common in nature and humans are no exception. Modern societies have created institutions to control cheating, but many situations remain where only intrinsic honesty keeps people from cheating and violating rules. Psychological, sociological and economic theories suggest causal pathways to explain how the prevalence of rule violations in people's social environment, such as corruption, tax evasion or political fraud, can compromise individual intrinsic honesty. Here we present cross-societal experiments from 23 countries around the world that demonstrate a robust link between the prevalence of rule violations and intrinsic honesty. We developed an index of the 'prevalence of rule violations' (PRV) based on country-level data from the year 2003 of corruption, tax evasion and fraudulent politics. We measured intrinsic honesty in an anonymous die-rolling experiment. We conducted the experiments with 2,568 young participants (students) who, due to their young age in 2003, could not have influenced PRV in 2003. We find individual intrinsic honesty is stronger in the subject pools of low PRV countries than those of high PRV countries. The details of lying patterns support psychological theories of honesty. The results are consistent with theories of the cultural co-evolution of institutions and values, and show that weak institutions and cultural legacies that generate rule violations not only have direct adverse economic consequences, but might also impair individual intrinsic honesty that is crucial for the smooth functioning of society.

Addiction potential of combustible menthol cigarette alternatives: a randomised cross-over trial.

INTRODUCTION: The Food and Drug Administration (FDA) has issued proposed product standards banning menthol as a characterising flavour in cigarettes and cigars. The public health benefits of these product standards may be attenuated by the role of plausible substitutes in the marketplace. Therefore, the present study examined the addiction potential of plausible combustible menthol alternatives compared with usual brand menthol cigarettes (UBMC). METHODS: Ninety-eight adult menthol cigarette smokers completed four visits, smoking their UBMC at the first session and three menthol cigarette alternatives in random order at the subsequent visits: (1) a preassembled menthol roll-your-own (mRYO) cigarette using menthol pipe tobacco and mentholated cigarette tube, (2) a menthol filtered little cigar (mFLC) and (3) a non-menthol cigarette (NMC). Measures of smoking topography, exhaled carbon monoxide (CO), craving and withdrawal, subjective effects and behavioural economic demand indices were assessed. RESULTS: Compared with UBMC, menthol cigarette alternatives resulted in different puffing topography and CO exposure (except mRYO), and lower levels of positive subjective experience and behavioural economic demand indices. Among the alternative products, participants reported the highest level of positive subjective experience and higher demand for mRYO, compared with mFLC and NMC. Similarly, participants were significantly more likely to want to try again, purchase and use the mRYO product regularly compared with mFLC and NMC. CONCLUSIONS AND RELEVANCE: mRYO cigarettes were the most highly rated cigarette alternative among study products, suggesting their potential appeal as a menthol cigarette substitute and needed inclusion of menthol pipe tobacco and cigarette tubes in FDA's proposed ban.

Understanding successful transition to independent living: A qualitative study of young adults with disabilities.

Background: Independent Living (IL) involves having choice and control over where and with whom one lives. People with disabilities are less likely to live independently than their peers without disabilities. Objective: The purpose of this study was to understand the perceptions of young adults with mobility disabilities regarding IL, how they define IL, and what advice they would give others considering living a more independent life. Method: Semi-structured interviews were conducted with six young adults with mobility disabilities who had successfully transitioned to living independently. A content analysis was used to identify emergent themes from the interviews. Results: Results indicate that participants had individualized perceptions of the definition of IL. Participants identified many barriers and facilitators to IL, including the physical layout of housing, available amenities, and social support. They recommended preparing for IL in advance and taking advantage of outside resources to enable a successful transition. Conclusion: Young adults with mobility disabilities define IL in various ways, which may have an impact on whether they consider their transition to IL successful. Findings can be used to guide recommendations for young people with disabilities to use to ensure a successful transition to IL.