Extreme drought impacts have been underestimated in grasslands and shrublands globally.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

The Portrayal of Premium Cigar Selling Propositions in Lifestyle Magazines: A Content Analysis.

INTRODUCTION: Although lifestyle magazines are an important marketing tool for premium cigars, little is known about their recent portrayal of the products. We expand on research conducted for the National Academies of Sciences, Engineering, and Medicine's Committee on Patterns of Use and Health Effects of "Premium Cigars" and Priority Research. AIMS AND METHODS: A content analysis of magazine covers, articles, and advertisements published in 2021 from Cigar Aficionado and Cigar Snob (five issues each) and Cigar Journal (three issues) assessed magazine themes and mentions of lower harm. Magazine covers (n = 14), advertisements (n = 105), and every fifth article (n = 45) were coded. RESULTS: In total, 92% of the magazine covers, 72.4% of advertisements, and 62.2% of articles had premium cigar content. Celebrities (e.g. musicians and actors) appeared on 92.9% of covers. The most common themes in the advertisements and articles were "high quality." Regarding article content, 80% portrayed the premium cigars' quality (e.g. superior materials), and the taste of featured products (e.g. "tones," "aromas," and "notes") was portrayed in 42.4%. While no articles described their health risks, 6.7% described the positive health effects of premium cigar use (e.g. stress relief and clear cognition). Additionally, a digital search of Cigar Snob and Cigar Aficionado for terms related to lower harm (e.g. "organic," "healthy," "clean," "pure," and "natural") found 7.7 mentions of lower-harm words per issue. CONCLUSIONS: Our findings indicate that lifestyle magazines are an important marketing strategy that promotes and normalizes premium cigar use as a high-quality product that can have positive health effects for users. IMPLICATIONS: Our manuscript characterized the premium cigar companies' use of selling propositions, including promoting the products' features, safety, taste, and flavors, as a part of their advertising promotion practices. Premium cigar companies used digital and print lifestyle magazines as marketing tools to promote and normalize the use of their products by emphasizing their high quality and positive health benefits (e.g. reducing stress). Premium cigars were promoted as a symbol of power and success, featured in advertisements of upscale social events (e.g. exclusive trade shows, social clubs, and lounges), and often juxtaposed with expensive alcohol, food, and other luxurious goods. Future research should assess if exposure to premium cigar content increases consumer appeal and detracts from the products' potential adverse health outcomes.

B.Y.O. Bees: Managing wild bee biodiversity in urban greenspaces.

As cities become more populated and the density of urban development increases, local biodiversity is threatened. Urban greenspaces have the capacity to preserve pollinator biodiversity, but the quality of support they provide depends on greenspace landscape attributes, including the availability of pollinator habitat and foraging resources. Wild native bees provide important pollination services to urban ecosystems, yet relatively little is known about how urban landscape management influences pollinator community composition and diversity. Our study explores how wild bee communities are affected by greenspace and landscape-level features like pollinator management practices, in urban greenspaces in and around Appleton Wisconsin: a mid-sized urban community spanning more than 100 sq. km. We sampled and identified native bees periodically between late-May 2017 and mid-September of 2018 using standardized arrays of pan traps at 15 sites around the city. We classified greenspaces based on their level of development (urban or suburban) and whether they were managed or unmanaged for increasing wild pollinator diversity. We quantified floral species diversity, floral color diversity, tree species diversity, and proximity of sites to open water for each site and used remotely sensed satellite data from both the USGS National Land Cover Database (NLCD) and the Normalized Difference Vegetation Index (NDVI). All variables were tested as potential correlates of wild bee abundance and species richness. Active pollinator management sites supported higher levels of bee abundance and richness. Notably, active greenspace management (e.g. planting native wildflowers) was a stronger correlate of bee abundance and richness than greenspace size and other landscape-level attributes. Within-greenspace attributes such as floral diversity, tree diversity, and proximity to open water contributed positively to both bee abundance and richness. Based on these findings, we suggest that urban greenspaces may be managed more efficiently and cost-effectively by focusing resources on active management by planting wildflowers, removing invasive species, creating nesting habitat, and providing water resources, rather than simply expanding in area.

Randomized trial on mindfulness training for smokers targeted to a disadvantaged population.

We report the results of a randomized trial comparing a novel smoking cessation treatment Mindfulness Training for Smokers (MTS) to a usual care therapy (Controls), which included the availability of a tobacco quit line and nicotine patches. Data were collected from 196 low socioeconomic status smokers in 2010-2011 in Madison, Wisconsin. Participants were randomized to either MTS or a telephonic quit line. The primary outcome was 6-month smoking abstinence measured by carbon monoxide breath testing and Time-Line Follow-Back. Among treatment initiators (randomized participants who participated in the intervention), abstinence rates were significantly different between the MTS (38.7%) and control (20.6%, p = .05) groups. Study limitations are also discussed. Results suggest that further study is warranted.

Providing premedical students with quality clinical and research experience: the Tobacco Science Scholars Program.

Undergraduate premedical students face a formidable decision as they work to determine whether to pursue a profession in medicine. Exposure to clinical medicine and research is essential to inform students what it might be like to be a physician. Undergraduates, however, face a number of obstacles to obtaining the kind of quality clinical and research experience needed to make an informed decision. Growing regulations designed to protect patient confidentiality, though undeniably important, pose a barrier to students seeking patient contact. Traditional passive physician shadowing often does not provide ample opportunities for one-on-one patient interaction or problem solving. Finally, research opportunities available to students typically are not associated with clinical work and therefore do not provide an experiential model of how empirical evidence informs medical practice. This report describes the University of Wisconsin School of Medicine and Public Health's Tobacco Science Scholars Program, a pilot program designed to address some of these barriers. While fulfilling institutional requirements for patient contact, the program provides students with an active model of clinical patient interaction and problem solving, with a research experience integrated into these clinical experiences so that undergraduates better understand how research informs clinical medicine.

Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients.

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/µL (range, 7-1500 cells/µL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

Safety and pharmacokinetics of brecanavir, a novel human immunodeficiency virus type 1 protease inhibitor, following repeat administration with and without ritonavir in healthy adult subjects.

Brecanavir (BCV) is a novel, potent protease inhibitor in development for the treatment of human immunodeficiency virus (HIV-1) infection with low nM in vitro 50% inhibitory concentrations (IC50s) against many multiprotease inhibitor resistant viruses. This study was a double-blind, randomized, placebo-controlled repeat-dose escalation to evaluate the safety, tolerability, and pharmacokinetics of BCV, with or without ritonavir (RTV), in 68 healthy subjects. Seven sequential cohorts (n=10) received BCV (50 to 600 mg) in combination with 100 mg RTV (every 12 h [q12h] or q24h) or alone at 800 mg q12h for 15 days. BCV alone or in combination with RTV was well tolerated, with no serious adverse events reported. The most common drug-related adverse event was headache. BCV was readily absorbed with median time to maximum concentration of drug in serum values ranging from 2.5 to 5.0 h postdose following single- and repeat-dose administration of BCV alone and BCV with RTV 100 mg. Geometric mean BCV accumulation ratios ranged from 1.4 to 1.56 following BCV-RTV q24h regimens and from 1.84 to 4.93 following BCV q12h regimens. BCV steady state was generally achieved by day 13 in all groups. All day 15 BCV-RTV trough concentration values in q12h regimens reached or surpassed the estimated protein-binding corrected in vitro IC50 target BCV concentration of 28 ng/ml for highly resistant isolates. The pharmacokinetic and safety profile of BCV-RTV supports continued investigation in HIV-1-infected subjects.

Single-dose safety and pharmacokinetics of brecanavir, a novel human immunodeficiency virus protease inhibitor.

Brecanavir (BCV, 640385) is a novel, potent protease inhibitor (PI) with low nanomolar 50% inhibitory concentrations against PI-resistant human immunodeficiency virus (HIV) in vitro. This phase I, double-blind, randomized, placebo-controlled, two-part single-dose study (first time with humans) was conducted to determine the safety, tolerability, and pharmacokinetics of BCV administered at 10 mg/ml in a tocopherol-polyethylene glycol succinate-polyethylene glycol 400-ethanol 50:40:10 solution. In part 1 of the study, single oral doses of BCV ranged from 25 mg to 800 mg. In part 2, single oral doses of BCV ranged from 10 mg to 300 mg and were coadministered with 100-mg oral ritonavir (RTV) soft gel capsules. Single doses of BCV and BCV/RTV were generally well tolerated. There were no severe adverse events (SAEs), and no subject was withdrawn due to BCV. The most commonly reported drug-related AEs during both parts of the study combined were gastrointestinal disturbances (similar to placebo) and headache. BCV was readily absorbed following oral administration with mean times to maximum concentration from >1 h to 2.5 h in part 1 and from 1.5 h to 3 h in part 2. Administration of BCV without RTV resulted in BCV exposures predicted to be insufficient to inhibit PI-resistant virus based on in vitro data. Coadministration of 300 mg BCV with 100 mg RTV, however, significantly increased the plasma BCV area under the concentration-time curve and maximum concentration 26-fold and 11-fold, respectively, achieving BCV concentrations predicted to inhibit PI-resistant HIV.