The older worker:Identifying a critical research agenda

The roles that older workers play in labour markets has received a great deal of policy and academic scrutiny in response to economic crises and demographic change. As a starting point, this focus has paradoxically resulted in insufficient attention to older workers themselves. The article is thus concerned with refocusing the agenda for research onto the older worker. Building on an extensive literature review, four gaps in knowledge are identified: who might be researched; what the focus of that research might be; the role of theory informing the research; and how the research might be conducted. The article identifies a particular need for research on ‘work’ as opposed to ‘retirement’ and how the changing nature of work may influence future patterns of later life labour market engagement and retirement. It is argued that better public policy will result from more critical and socially embedded research that recognises the heterogeneity of ‘older workers’ and their motivations

Student Independent Projects: Tourism Studies 2013

The B.A. in Tourism Studies program offered at Grenfell Campus, Memorial University of Newfoundland prepares and positions students for exciting, competitive and successful careers in a wide range of vocations that manage, influence and direct tourism at all levels including lodging, food services, transportation, meetings and conventions, special events, entertainment, sports and recreation, heritage and culture, public policy and administration, international relations, and information communications and technology (ICT). Tourism 4950 - Special Project in Tourism, an important component of the Tourism Studies program is available to students who have completed 78 credit hours, and have officially declared a Major in Tourism Studies, a Minor in Tourism Studies, or have been accepted into the Advanced Diploma Program in Tourism Studies. Under the guidance of a faculty member, a student completes an independent research project and produces a report. The project topic must have the approval of the Chair of the Tourism Studies program. The collection of projects undertaken by the students in the Advanced Diploma and B.A. in Tourism Studies program reflects the multisectoral nature of the tourism industry and the invaluable knowledge and experiences the students have acquired. The projects underscore the interdisciplinary, comparative and international approach, dealing with both theoretical aspects and empirical case studies in the tourism industry. Jessica’s Greenwood’s main focus of the paper is on the roles that Hospitality Newfoundland and Labrador (HNL) plays in the tourism industry since its establishment in 1983 in the province of Newfoundland and Labrador. The paper highlights the interdependence, interrelationships and partnerships that exist among some of the institutions in spite of the differences in their geographical levels of operation. Wendy Brake’s research explores and describes the growth of tourism in Port au Port, Lark Harbour and Sally’s Cove communities of Western Newfoundland She also discusses the potential negative impacts that an oil and gas industry, if developed, could have on the tourism industry. Akua Anyemedu’s paper analyses and discusses the roles of some selected institutions in sustainable tourism development in Ghana. The major finding is that the communities epitomize the paradigm shift in sustainable tourism development and the institutions supporting them have also pointed them in the right direction of development. Chelsea Kohli’s paper discussed the negative and positive impacts of Iceland’s nature-based tourism industry and provided recommendations for improvement. The research identifies Iceland’s greatest weaknesses are in its planning and management, while its strengths lie primarily in its marketing and advertising sector. It is quite remarkable that the Tourism Studies program has reached this important milestone in six years. On behalf of the faculty of Tourism Studies, I congratulate all the students who have successfully completed the Special Project in Tourism and wish them a future without boundaries and every success in their endeavors. The advisory and administrative support provided by Dr. Sandra Wright and Krista Hansen-Robitschek, Head and Secretary of the Division of Social Science respectively, are deeply appreciated. Dr. Edward Addo deserves commendation for supervising the projects undertaken by Jessica Greenwood, Wendy Brake and Akua Anyemedu. My didactic experiences have been enhanced by supervising the project undertaken by Chelsea Kohli. Roselyne Okec

Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development

Bruton’s tyrosine kinase (Btk) is a nonreceptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Preclinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and preclinical characterization of a potent, selective, and noncovalent Btk inhibitor currently in clinical development. GDC-0853 (<b>29</b>) suppresses B cell- and myeloid cell-mediated components of disease and demonstrates dose-dependent activity in an <i>in vivo</i> rat model of inflammatory arthritis. It demonstrates highly favorable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria. On the basis of its potency, selectivity, long target residence time, and noncovalent mode of inhibition, <b>29</b> has the potential to be a best-in-class Btk inhibitor for a wide range of immunological indications

Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development

Bruton’s tyrosine kinase (Btk) is a nonreceptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Preclinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and preclinical characterization of a potent, selective, and noncovalent Btk inhibitor currently in clinical development. GDC-0853 (<b>29</b>) suppresses B cell- and myeloid cell-mediated components of disease and demonstrates dose-dependent activity in an <i>in vivo</i> rat model of inflammatory arthritis. It demonstrates highly favorable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria. On the basis of its potency, selectivity, long target residence time, and noncovalent mode of inhibition, <b>29</b> has the potential to be a best-in-class Btk inhibitor for a wide range of immunological indications

Battling Btk Mutants With Noncovalent Inhibitors That Overcome Cys481 and Thr474 Mutations

The Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib has shown impressive clinical efficacy in a range of B-cell malignancies. However, acquired resistance has emerged, and second generation therapies are now being sought. Ibrutinib is a covalent, irreversible inhibitor that modifies Cys481 in the ATP binding site of Btk and renders the enzyme inactive, thereby blocking B-cell receptor signal transduction. Not surprisingly, Cys481 is the most commonly mutated Btk residue in cases of acquired resistance to ibrutinib. Mutations at other sites, including Thr474, a gatekeeper residue, have also been detected. Herein, we describe noncovalent Btk inhibitors that differ from covalent inhibitors like ibrutinib in that they do not interact with Cys481, they potently inhibit the ibrutinib-resistant Btk C481S mutant <i>in vitro</i> and in cells, and they are exquisitely selective for Btk. Noncovalent inhibitors such as GNE-431 also show excellent potency against the C481R, T474I, and T474M mutants. X-ray crystallographic analysis of Btk provides insight into the unique mode of binding of these inhibitors that explains their high selectivity for Btk and their retained activity against mutant forms of Btk. This class of noncovalent Btk inhibitors may provide a treatment option to patients, especially those who have acquired resistance to ibrutinib by mutation of Cys481 or Thr474