Women’s Leader Development Programs: Current Landscape and Recommendations for Future Programs

The gender gap in leadership positions is unjust and unproductive. In this paper, we focus on one solution – leader development. We leverage a content analysis of the top U.S. women’s leader development programs (WLDPs) and literature on women’s leadership and leader development. We provide seven evidence-based recommendations for WLDPs including: identify measurable objectives, increase access for emerging leaders, cultivate a paradox mindset around leader and gender identity, leverage experiential learning, expand networks, educate about second-generation gender bias, and align evaluations. We urge administrators to adopt our recommendations as one piece of a systematic effort to pursue gender parity in leadership

Barriers and facilitators associated with implementing interventions to support oral anticancer agent adherence in academic and community cancer center settings

Purpose The goal of this study is to determine barriers and facilitators to the implementation of medication adherence interventions to support cancer patients taking novel, targeted oral anticancer agents (OAAs). Methods We conducted qualitative interviews using a semi-structured guide from the Consolidated Framework for Implementation Research (CFIR). We used purposive sampling to identify clinicians (physicians, pharmacists, nurse practitioners, nurses) and administrators (leadership from medicine, pharmacy, and nursing) who delivered care and/or oversee care delivery for patients with chronic leukemia prescribed an OAA. Results A total of 19 individuals participated in an interview (12 clinicians and 7 administrators), with 10 primarily employed by an academic cancer center; 5 employed by the community cancer center; and 4 employed by the integrated health-system specialty pharmacy. Barriers identified included low awareness of adherence interventions, difficulty in adherence measurement, complexity of designing and implementing a structured adherence intervention, and competing priorities. Facilitators identified included support of hospital administrators, value for pharmacists, and willingness to embrace change. Participants also made recommendations moving forward including standardizing workflow, designating champions, iterating implementation strategies, and improving communication between clinicians and with patients. Conclusion Individual and system level factors were identified as determinants of implementation effectiveness of medication adherence interventions. A multidisciplinary advisory panel will be assembled to design comprehensive and actionable strategies to refine and implement a structured intervention to improve medication adherence in cancer patients

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

JWH-018 and M1 decreased mouse locomotor activity in a CB1R-dependent manner, similar to Δ⁹-THC.

<p><b>A.</b> Intraperitoneal (i.p.) administration of 3 mg/kg JWH-018, 10 mg/kg JWH-018 M1, and 30 mg/kg Δ⁹-THC decreased locomotor activity relative to vehicle controls over a 10 h time course, beginning 60 min after injection. <b>B.</b> Area under the curve data generated from the 10 h time-course shows 3 mg/kg JWH-018, 10 mg/kg JWH-018 M1, and 30 mg/kg Δ⁹-THC significantly decrease locomotor activity relative to vehicle controls (*<i>P</i><0.05 vs. vehicle controls, Kruskal-Wallis one-way ANOVA with Tukey HSD test, n = 5). Co-administration of each cannabinoid with the CB1R-preferring antagonist/inverse agonist AM251 (10 mg/kg) restored locomotor activity to vehicle control levels.</p

Structures of JWH-018 and six JWH-018 hydroxylated products.

<p><b>A. JWH-018</b> [(1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone] <b>B. M1</b> [(4-hydroxy-1-pentyl-1H-indol-3-yl)(naphthalen-1-yl)methanone] <b>C. M2</b> [(5-hydroxy-1-pentyl-1H-indol-3-yl)(naphthalen-1-yl)methanone] <b>D. M3</b> [(6-hydroxy-1-pentyl-1H-indol-3-yl)(naphthalen-1-yl)methanone] <b>E. M4</b> [(7-hydroxy-1-pentyl-1H-indol-3-yl)naphthalen-1-yl)methanone] <b>F. M5</b> [(1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone] <b>G. M6</b> [5-(3-(1-naphthoyl)-1H-indol-1-yl)pentanoic acid].</p