E pluribus unum : impact entrepreneurship as a solution to grand challenges

Insufficiency of research and theory on the relationship between entrepreneurship and grand challenges means that we know little about who engages and what repertoires of actions they take to tackle socioenvironmental challenges that transcend firms, markets, and nations, and what sorts of solutions they create. Drawing on the five articles featured in this symposium-and focusing especially on their protagonists or actors, the actions these actors take, and their achievements-we begin to conceptualize an impact entrepreneurship perspective. Following the tenet of e pluribus unum ("out of many, one") and adhering to the doctrine that diverse, decentralized human effort can improve the world, our impact entrepreneurship perspective refers to the development of solutions to grand challenges, in a financially, socially, and environmentally sustainable fashion. All in all, then, this symposium provides a starting point to discuss, conceptualize, study, interpret, and enrich our understanding of impact entrepreneurship and collective action to address grand challenges

Values-Based Rivalry: A Theoretical Framework of Rivalry Between Activists and Firms

In this article we develop a theoretical framework to explain values-based rivalry between activists and firms by integrating and advancing key insights from competitive dynamics and social activist research. The first part of our framework conceptualizes the unique tensions, actions, and responses that characterize values-based rivalry and distinguish it from rivalry between firms. The second part of our framework conceptualizes the role of managers’ perceptions in shaping their firms’ likelihood of responding to activists’ actions during values-based rivalry. Overall, our conceptualization primarily expands competitive dynamics research to account for rivalry between dissimilar actors and, in doing so, broadens social activist research to account for such rivalry

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The interpretability of family history reports of alcoholism in general community samples:findings in a midwestern U.S. twin birth cohort

BACKGROUND: Although there is a long tradition in alcoholism research of using family history ratings, the interpretability of family history reports of alcoholism from general community samples has yet to be established. METHODS: Telephone interview data obtained from a large cohort of female like-sex twins (N = 3787, median age 22) and their biological parents (N = 2928, assessed at twins’ median age 15) were analyzed to determine agreement between parent self-report, parent ratings of coparent, and twin narrow (alcohol problems) versus broad (problem or excessive drinking) ratings of each parent. RESULTS: In European ancestry (EA) families, high tetrachoric correlations were observed between twin and cotwin ratings of parental alcohol problems, between twin and parent ratings of coparent alcohol problems using symptom-based and single-item assessments, as well as moderately high correlations between twin and both mother and father self-reports. In African American (AA) families, inter-rater agreement was substantially lower than for EA families, with no cases where father ratings of maternal alcohol problems agreed with either twin ratings or mother self-report; and both cotwin agreement and mother-twin agreement were reduced. Differences between EA and AA families were not explained by differences in years of cohabitation with father or mother’s education; however, underreporting of problems by AA parents may have contributed. CONCLUSIONS: Results support the use of family history ratings of parental alcoholism in general community surveys for European ancestry families, but suggest that family history assessment in African American families requires improved methods

Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenledeucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-y in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenledeucel cellular kinetics, including maximum concentration and persistence (r(2) < 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses <1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenledeucel in patients with r/r B-ALL or r/r DLBCL