Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration

Lung cancer is one of the most common fatal diseases in the developed world. The disease is rarely cured by currently available therapies, with an overall survival rate of ∼10%. Characterizing novel proteins that offer crucial insights into the processes of lung tumour invasion and metastasis may therefore provide much-needed prognostic markers, and influence therapeutic strategies. Aberrant function of the integrin family of heterodimeric cell surface receptors is a common theme in cancer--investigation into novel integrin activity regulators may offer crucial insights into the processes of tumour invasion and metastasis and may reveal insights into potential therapeutic targets. We previously described that depletion of the novel multi-transmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER), inactivates endogenous beta1 integrin affinity, reducing cell adhesion. We now show that depletion of Fam38A, also now known as Piezo1, causes anchorage independence and a switch to a reduced integrin-dependent mode of cell migration/invasion, a novel phenotype for this integrin-regulating protein. Normal lung epithelial cells show increased rates of migration by 2D time-lapse microscopy and increased capacity to invade into matrigel, despite having decreased integrin affinity. We confirm greatly depleted Fam38A expression in small cell lung cancer (SCLC) lines where a form of reduced integrin-dependent migration, i.e. amoeboid migration, is a known phenotype. We propose that loss of Fam38A expression may cause increased cell migration and metastasis in lung tumours

The implementation evaluation of primary care groups of practice: a focus on organizational identity

<p>Abstract</p> <p>Background</p> <p>Since 2002 the Health Ministry of Québec (Canada) has been implementing a primary care organizational innovation called 'family medicine groups'. This is occurring in a political context in which the reorganization of primary care is considered necessary to improve health care system performance. More specifically, the purpose of this reform has been to overcome systemic deficiencies in terms of accessibility and continuity of care. This paper examines the first years of implementation of the family medicine group program, with a focus on the emergence of the organizational identity of one of the pilot groups located in the urban area of Montreal.</p> <p>Methods</p> <p>An in-depth longitudinal case study was conducted over two and a half years. Face to face individual interviews with key informants from the family medicine group under study were conducted over the research period considered. Data was gathered throuhg observations and documentary analysis. The data was analyzed using temporal bracketing and Fairclough's three-dimensional critical discourse analytical techniques.</p> <p>Results</p> <p>Three different phases were identified over the period under study. During the first phase, which corresponded to the official start-up of the family medicine group program, new resources and staff were only available at the end of the period, and no changes occurred in medical practices. Power struggles between physicians and nurses characterized the second phase, resulting in a very difficult integration of advanced nurse practitioners into the group. Indeed, the last phase was portrayed by initial collaborative practices associated with a sensegiving process prompted by a new family medicine group director.</p> <p>Conclusions</p> <p>The creation of a primary care team is a very challenging process that goes beyond the normative policy definitions of who is on the team or what the team has to do. To fulfil expectations of quality improvement through team-based care, health care professionals who are required to work together need shared time/space contexts to communicate; to overcome interprofessional and interpersonal conflicts; and to make sense of and define who they collectively are and what they do as a clinical team.</p

Environmental criminology and the potential for reducing opportunities for bushfire arson

Since the 1980s, the incidence of wildfires (forest fires), across the World has significantly increased (Jensen) and climate change has been implicated in this trend (UNEP). In recent years, major wild fires have occurred in the United States, Canada, Australia, Indonesia, Latin America, Spain, Portugal, Greece, Iran, Russia and most recently, in Israel. In Australia, wildfires or forest fires are known as bushfires, and approximately 60 000 occur each year. Only 6 per cent are ‘natural fires’, while 90 per cent are the result of people's actions. Significantly, deliberate ignitions; incendiary (maliciously lit fires) and suspicious fires account for 50 per cent of known fire causes (Bryant). Internationally, research in the field of bushfire arson prevention is currently dominated by offender-based approaches, which largely rely on incomplete and limited insights from a minority (less than 1 per cent) of arsonists who have been apprehended (Ogloff Tomison and Jones). This article explores how theories from environmental criminology can be used to understand and analyse place-based factors associated with deliberately lit bushfires. It also presents findings from a recent workshop conducted at the Australian Symposium on Bushfire Arson Prevention in order to further contextualise the relevance of environmental criminology to the analysis and reduction of bushfire arson