Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Social capital theory: a cross-cutting analytic for teacher/therapist work in integrating children's services?

Reviewing relevant policy, this article argues that the current 'integration interlude' is concerned with reformation of work relations to create new forms of 'social capital'. The conceptual framework of social capital has been used by government policy-makers and academic researchers to examine different types, configurations and qualities of relationships, including professional relations, and how these may function as resources. Focusing on the co-work of teachers and speech and language therapists, this analysis introduces social capital as a means of understanding the impact of integrating children's services on professional practitioner groups and across agencies. Social capital theory is compared to alternative theoretical perspectives such as systems and discourse theories and explored as an analytic offering a multi-level typology and conceptual framework for understanding the effects of policy and governance on interprofessional working and relationships. A previous application of social capital theory in a literature review is introduced and analysed, and instances of the additionality provided by a social capital analysis is offered. The article concludes that amongst the effects of current policy to re-design children's services are the reconstruction of professionals' knowledge/s and practices, so it is essential that such policy processes that have complex and far-reaching effects are transparent and coherent. It is also important that new social capital relations in children's services are produced by groups representative of all involved, importantly including those practitioner groups charged in policy to work differently together in future integrated services

The Expanding Fireball of Nova Delphini 2013

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting from one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc from the Sun.Comment: Published in Nature. 32 pages. Final version available at http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Corporate Entrepreneurship:From Structures to Mindset

Corporate entrepreneurship dispersed throughout an organization and leveraging the entrepreneurial potential of all its employees bears significant benefits for those organizations that embrace it. However, it appears more difficult to instill and requires strong investment in the development of human capital and entrepreneurial mindset among the employees and across the organization. In this chapter, we discuss the essence of corporate entrepreneurship mindset and show that across an organization, there might be different entrepreneurial mindsets that correspond to different people, opportunities, and contexts. Although different, they all lead to enactment of entrepreneurial projects. This chapter, thus, contributes to the discussion regarding the nature of corporate entrepreneurial mindsets, and their development and stimulation within an organization, from both academic and practical view

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

A scoping review of the implications of adult obesity in the delivery and acceptance of dental care.

Background Due to the increasing prevalence of obesity within the general population it is presumed that the prevalence of overweight and obese adults accessing dental services will also increase. For this reason dentists need to be aware of implications of managing such patients.Methods A scoping review was carried out. Both Medline via OVID and Scopus databases were searched along with grey literature databases and the websites of key organizations. Inclusion and exclusion criteria were established. The data were collected on a purpose-made data collection form and analysed descriptively.Results The review identified 28 relevant published articles and two relevant items of grey literature. Following review of this literature three themes relating to adult obesity in the delivery and acceptance of dental care emerged; clinical, service delivery and patient implications. The majority of the papers focused on the clinical implications.Conclusion On the topic of adult obesity and dental care, the majority of published and grey literature focuses on the clinical implications. Further research is needed on both the patients' perspectives of being overweight or obese and the delivery and acceptance of dental care and the service delivery implications

Victim awareness : re-examining a probation fundamental

‘Ensuring offenders' awareness of the effects of crime on the victims of crime and the public’ is one of five stated aims of the National Probation Service of England and Wales and specifically undertaking victim awareness work is an expectation of the service’s work. The nature and putative value of such work appears to be rarely questioned however. It is argued that ‘victim awareness’ is a confused concept in terms of its rationale, definition, and empirical basis as a criminogenic need. These issues are evaluated and the practice implications discussed. A possible model of victim awareness work is described

How university’s activities support the development of students’ entrepreneurial abilities: case of Slovenia and Croatia

The paper reports how the offered university activities support the development of students’ entrepreneurship abilities. Data were collected from 306 students from Slovenian and 609 students from Croatian universities. The study reduces the gap between theoretical researches about the academic entrepreneurship education and individual empirical studies about the student’s estimation of the offered academic activities for development of their entrepreneurial abilities. The empirical research revealed differences in Slovenian and Croatian students’ perception about (a) needed academic activities and (b) significance of the offered university activities, for the development of their entrepreneurial abilities. Additionally, the results reveal that the impact of students’ gender and study level on their perception about the importance of the offered academic activities is not significant for most of the considered activities. The main practical implication is focused on further improvement of universities’ entrepreneurship education programs through selection and utilization of activities which can fill in the recognized gaps between the students’ needed and the offered academic activities for the development of students’ entrepreneurial abilities