CEO Transformational Leadership and Corporate Social Responsibility

The overall purpose of this study is to apply transformational leadership theory to improve our understanding of the potential role of CEOs in determining the extent to which their firms engage in corporate social responsibility (CSR). We generate a theoretical argument for the existence of relationships between aspects of transformational leadership and CSR, which we test using data from 56 U.S. and Canadian firms. CEO intellectual stimulation (but not CEO charismatic leadership) is found to be positively associated with the propensity of the firm to engage in "strategic" CSR, or those CSR activities that are most likely to be related to the firm's corporate and business-level strategies. Thus, studies that ignore the role of leadership in CSR may generate imprecise conclusions regarding the antecedents and consequences of these activities. We conclude that there is a need for additional multidisciplinary research bridging micro- and macro-level conceptualizations of the role of leadership in CSR.

Analytic lymph node number establishes staging accuracy by occult tumor burden in colorectal cancer.

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden. METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category were defined by multivariable polytomous and semi-parametric polytomous logistic regression. RESULTS: Occult tumor burden stratified this pN0 cohort into categories of low (60%; recurrence rate (RR) = 2.3% [95% CI 0.1-4.5%]), intermediate (31%; RR = 33.3% [23.7-44.1%]), and high (9%; RR = 68.0% [46.5-85.1%], P \u3c 0.001) risk of recurrence. Beyond race and T stage, the number of analytic nodes was an independent marker of risk category (P \u3c 0.001). When \u3e12 nodes were analyzed, occult tumor burden almost completely resolved prognostic risk classification of pN0 patients. CONCLUSIONS: The prognostic utility of occult tumor burden assessed by GUCY2C RT-qPCR is dependent on the number of analytic lymph nodes

Predicting pilot error on the flight deck: Validation of a new methodology and a multiple methods and analysts approach to enhancing error prediction sensitivity

The Human Error Template (HET) is a recently developed methodology for predicting designed induced pilot error. This article describes a validation study undertaken to compare the performance of HET against three contemporary Human Error Identification (HEI) approaches when used to predict pilot errors for an approach and landing task and also to compare individual analyst error predictions to an approach to enhancing error prediction sensitivity: the multiple analysts and methods approach, whereby multiple analyst predictions using a range of HEI technique are pooled. The findings indicate that, of the four methodologies used in isolation, analysts using the HET methodology offered the most accurate error predictions, and also that the multiple analysts and methods approach was more successful overall in terms of error prediction sensitivity than the three other methods but not the HET approach. The results suggest that when predicting design induced error, it is appropriate to use domain specific approaches and also a toolkit of different HEI approaches and multiple analysts in order to heighten error prediction sensitivity

APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis

Dentistry for Nigerians with special needs: an overview

There are approximately 25 million residents with disabilities in Nigeria. Social inclusion of individuals with disabilities is difficult since societal views of these persons are in terms of charity and welfare rather than functioning members of a community. While there are no national studies of the dental needs of individuals with disabilities in Nigeria, there are reports of local studies of patients with disabilities which indicate a greater incidence of management difficulties as well as the need for improved oral hygiene and restorative services. Nevertheless, a study of practitioner involvement in the care of individuals with disabilities reported limited preparation of dental students to provide service for this population. Some organizations, such as the Special Olympics Healthy Athletes Special Smiles and the Smile Train, have set up programmes, both educational and service, to address some of their oral health issues. It is recommended that there is a need to identify the availability of current dental service centers for individuals with disabilities, establish a national organization to stimulate an awareness of the varied needs of individuals with disabilities and real programs in schools to prepare dental students to care for individuals with disabilities. Examples of dental education accreditation standards in other countries are used as models for the improvement in the preparation of dental students to provide services for individuals with special needs

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Corrigendum to “Implementation of tidal turbines in MIKE 3 and Delft3D models of Pentland Firth & Orkney waters” [Ocean Coast. Manag. 147 (2017) 21–36]

© 2017 Elsevier Ltd The authors regret that a software error caused incorrect predictions for the effects of tidal turbines in Delft3D. The predictions without turbines are unaffected, as are those from the MIKE 3 model. The overall conclusions of the article remain valid. Figs. 12–15 as published are incorrect. Replacements for Figs. 12–14 are presented here. Following this correction the differences in the effects of energy extraction between the two models are much smaller. As a result the discussion of these differences in Section 6 should be disregarded, and Fig. 15 is no longer required. The authors would like to apologise for any inconvenience caused. The version of the code for adding turbines to Delft3D that is publicly available has been corrected, and anybody using this for their own work is urged to download the latest version. [Figure presented] Fig. 12: (a) 400 turbines in the Inner Sound, viewed through the MIKE Zero GUI; (b) The same 400 turbines represented as porous plates for Delft3D. Higher values of the closs parameter, shown by bluer colours, indicate plates with higher drag. [Figure presented] Fig. 13: Changes in mean current speeds over 28 days as a result of adding turbines. [Figure presented] Fig. 14: Change in mean bed stress magnitude over 28 days as a result of adding turbines, expressed as a proportion of the value without turbines

Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. GUCY2C CAR-T cells provided long-term protection against lung metastases of murine colorectal cancer cells engineered to express human GUCY2C in a syngeneic mouse model. GUCY2C murine CAR-T cells recognized and killed human colorectal cancer cells endogenously expressing GUCY2C, providing durable survival in a human xenograft model in immunodeficient mice. Thus, we have identified a human GUCY2C-specific CAR-T cell therapy approach that may be developed for the treatment of GUCY2C-expressing metastatic colorectal cancer