Purpose-Driven Leadership for the 21st Century: Transitioning to a Purpose-First Economy Through the New Business Logic

Welcome to the 3rd Annual Leaders on Purpose CEO Study for 2020. This year’s edition expands on insights of our previous two studies and also introduces new concepts emerging from the burgeoning field of purpose-driven leadership. The COVD-19 pandemic and its attendant challenges feature prominently, which is why we are excited to spotlight some of the groundbreaking work that is being done to address this still unfolding public health crisis. This year, we had an opportunity to speak with 15 paradigm-changing leaders. This is our most diverse set of interviewees yet, representing perspectives that span the globe and reflect the rich variety of cultures comprising its populous. The Leaders on Purpose 2020 CEO Study provides insight into the role that purpose-driven organizations play in society and illustrates how fundamental an organization’s purpose is to survival. This research also identifies and analyzes the ways that corporate leaders leverage purpose to realize their dual binary ambitions of achieving financial success and promoting positive social change. The Leaders on Purpose 2020 CEO Study provides insight into the role that purpose-driven organizations play in society and illustrates how fundamental an organization’s purpose is to survival. This research also identifies and analyzes the ways that corporate leaders leverage purpose to realize their dual binary ambitions of achieving financial success and promoting positive social change. This year’s study focuses on four key areas of purpose in business practice. Navigating Disruption with Purpose-Driven Leadership, Corporate Culture, Purpose and the Pandemic, The Corporate Purpose Moment in Strategy and Chapter 4: Partnerships for Acceleration and Scale

Shelley's Heart: Experiences in Designing a Multi-Reader Locative Narrative

Locative Narratives tie elements of the narrative to physical locations that users must visit in order to experience. While single reader locative stories and multiplayer locative games are increasingly common, the intersection of these, multi-reader locative narratives, are much less common. This work will analyse prior works of Locatives Narrative and Multi-User Locative Games in order to develop a model to describe Multi-Reader Locative Narrative and present the design for Shelley's Heart (an in-development multi-reader locative narrative) in the terms of this model

Towards concolic testing for hybrid systems

Hybrid systems exhibit both continuous and discrete behavior. Analyzing hybrid systems is known to be hard. Inspired by the idea of concolic testing (of programs), we investigate whether we can combine random sampling and symbolic execution in order to effectively verify hybrid systems. We identify a sufficient condition under which such a combination is more effective than random sampling. Furthermore, we analyze different strategies of combining random sampling and symbolic execution and propose an algorithm which allows us to dynamically switch between them so as to reduce the overall cost. Our method has been implemented as a web-based checker named HYCHECKER. HYCHECKER has been evaluated with benchmark hybrid systems and a water treatment system in order to test its effectiveness.CPCI-S(ISTP)[email protected]; [email protected]

High seroprevalence of Toxoplasma gondii infection in a subset of Mexican patients with work accidents and low socioeconomic status

<p>Abstract</p> <p>Background</p> <p><it>Toxoplasma gondii </it>has been associated with reflex impairment and traffic accidents. It is unknown whether <it>Toxoplasma </it>infection might be associated with work accidents. Therefore, using a case-control seroprevalence study design, 133 patients with a recent work accident and 266 control subjects of the general population from the same region were examined with enzyme-linked immunoassays for the presence and levels of anti-<it>Toxoplasma </it>IgG antibodies and anti-<it>Toxoplasma </it>IgM antibodies. Socio-demographic, work, clinical and behavioral characteristics from each worker were obtained.</p> <p>Results</p> <p>Eleven (8.3%) of 133 patients, and 14 (5.3%) of 266 controls had anti-<it>T. gondii </it>IgG antibodies. Anti-<it>T. gondii </it>IgG levels were higher than 150 IU/ml in 8 (6%) patients and 10 (3.8%) controls. Anti-<it>T. gondii </it>IgM antibodies were found in one (0.8%) of the workers, and in 6 (2.3%) of the controls. No statistically significant differences in the IgG seroprevalences, frequencies of high IgG levels, and IgM seroprevalences among patients and controls were found. In contrast, a low socio-economic level in patients with work accidents was associated with <it>Toxoplasma </it>seropositivity (<it>P </it>= 0.01). Patients with work accidents and low socioeconomic status showed a significantly (OR = 3.38; 95% CI: 0.84-16.06; <it>P </it>= 0.04) higher seroprevalence of <it>T. gondii </it>infection than controls of the same socioeconomic status (15.1% vs. 5%, respectively). Multivariate analysis showed a positive association of <it>T. gondii </it>infection with boar meat consumption (OR = 3.04; 95% CI: 1.03-8.94; <it>P </it>= 0.04). In contrast, a negative association between <it>T. gondii </it>infection and national trips (OR = 0.40; 95% CI: 0.17-0.96; <it>P </it>= 0.04), sausage consumption (OR = 0.20; 95% CI: 0.05-0.68; <it>P </it>= 0.01), and ham consumption (OR = 0.16; 95% CI: 0.05-0.51; <it>P </it>= 0.002) was found.</p> <p>Conclusions</p> <p>In the study described here seropositivity to <it>T. gondii </it>was associated to work accidents in a subset of patients with low socioeconomic status. This is the first report of an association of <it>T. gondii </it>infection and work accidents. Further studies to confirm our results are needed. Results may help in designing optimal prevention strategies to avoid <it>T. gondii </it>infection.</p

A Simple Standard for Sharing Ontological Mappings (SSSOM).

Despite progress in the development of standards for describing and exchanging scientific information, the lack of easy-to-use standards for mapping between different representations of the same or similar objects in different databases poses a major impediment to data integration and interoperability. Mappings often lack the metadata needed to be correctly interpreted and applied. For example, are two terms equivalent or merely related? Are they narrow or broad matches? Or are they associated in some other way? Such relationships between the mapped terms are often not documented, which leads to incorrect assumptions and makes them hard to use in scenarios that require a high degree of precision (such as diagnostics or risk prediction). Furthermore, the lack of descriptions of how mappings were done makes it hard to combine and reconcile mappings, particularly curated and automated ones. We have developed the Simple Standard for Sharing Ontological Mappings (SSSOM) which addresses these problems by: (i) Introducing a machine-readable and extensible vocabulary to describe metadata that makes imprecision, inaccuracy and incompleteness in mappings explicit. (ii) Defining an easy-to-use simple table-based format that can be integrated into existing data science pipelines without the need to parse or query ontologies, and that integrates seamlessly with Linked Data principles. (iii) Implementing open and community-driven collaborative workflows that are designed to evolve the standard continuously to address changing requirements and mapping practices. (iv) Providing reference tools and software libraries for working with the standard. In this paper, we present the SSSOM standard, describe several use cases in detail and survey some of the existing work on standardizing the exchange of mappings, with the goal of making mappings Findable, Accessible, Interoperable and Reusable (FAIR). The SSSOM specification can be found at http://w3id.org/sssom/spec. Database URL: http://w3id.org/sssom/spec

LMTK3 confers chemo-resistance in breast cancer

Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment. In a mouse model we showed that ectopic overexpression of LMTK3 decreases the efficacy of doxorubicin in reducing tumor growth. Interestingly, breast cancer cells overexpressing LMTK3 delayed the generation of double strand breaks (DSBs) after exposure to doxorubicin, as measured by the formation of γH2AX foci. This effect was at least partly mediated by decreased activity of ataxia-telangiectasia mutated kinase (ATM) as indicated by its reduced phosphorylation levels. In addition, our RNA-seq analyses showed that doxorubicin differentially regulated the expression of over 700 genes depending on LMTK3 protein expression levels. Furthermore, these genes were found to promote DNA repair, cell viability and tumorigenesis processes / pathways in LMTK3-overexpressing MCF7 cells. In human cancers, immunohistochemistry staining of LMTK3 in pre- and postchemotherapy breast tumor pairs from four separate clinical cohorts revealed a significant increase of LMTK3 following both doxorubicin and docetaxel based chemotherapy. In aggregate, our findings show for the first time a contribution of LMTK3 in cytotoxic drug resistance in breast cancer

CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.

CD4+ regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, contribute to tumour immunosuppression but are also required for immune homeostasis. There is interest in developing therapies that selectively target the immunosuppressive function of Treg cells within tumours without disrupting their systemic anti-inflammatory function. High levels of expression of chemokine (C-C motif) receptor 8 (CCR8) discriminate Treg cells within tumours from those found in systemic lymphoid tissues. It has recently been proposed that disruption of CCR8 function using blocking anti-CCR8 antibodies results in reduced accumulation of Treg cells within tumours and disruption of their immunosuppressive function. Here, using Ccr8-/- mice, we show that CCR8 function is not required for Treg cell accumulation or immunosuppression in the context of syngeneic MC38 colorectal adenocarcinoma and B16 melanoma tumours. We observed high levels of CCR8 expression on tumour-infiltrating Treg cells which were abolished in Ccr8-/- mice. High levels of CCR8 marked cells with high levels of suppressive function. However, whereas systemic ablation of Treg cells resulted in strikingly diminished tumour burden, growth of subcutaneously implanted tumours was unaffected by systemic CCR8 loss. Consistently, we observed minimal impact of systemic CCR8 ablation on the frequency, phenotype and function of tumour-infiltrating Treg cells and conventional T (Tconv) function. These findings suggest that CCR8 is not required for Treg cell accumulation and immunosuppressive function within tumours and that depletion of CCR8+ Treg cells rather than blockade of CCR8 function is a more promising avenue for selective immunotherapy