CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

The assumption that mesenchymal stromal cell (MSC)-based therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo significant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading. Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5’-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identified as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration. These results suggest that MSC migration is controlled by CD73 CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfil their regenerative functions.

Reconceiving the good life : the key to sustainable globalisation

Resource-intensive, high-carbon, Western lifestyles are frequently criticised as unsustainable and deeply unsatisfying. However, these lifestyles are still attractive to the majority of Westerners and to a high proportion of the developing world’s middle classes. This paper argues that the imminent threat of catastrophic climate change constitutes an immediate political, economic and ethical challenge for citizens of the developed world that cannot be tackled by appeals to asceticism or restraint. There can be no solution to climate change until sustainable conceptions of the good life are developed that those in the west want to live and which others might want to live. While the ultimate solution to climate change is the development of low carbon lifestyles, it is important that government initiatives, governance arrangements and economic incentives support rather than undermine that search. Like the global financial crisis, the climate change crisis also demonstrates what happens when weaknesses in national, corporate and professional governance are exacerbated by weaknesses in global governance. In tackling the latter, it is critical the mistakes now evidenced in the former are avoided – including a rethinking of carbon market and carbon tax alternatives. It is also critical that individuals must take responsibility for their actions as consumers, voters and investors.

A Python package for Bayesian estimation using Markov Chain Monte Carlo

Markov chain Monte Carlo (MCMC) estimation provides a solution to the complex integration problems that are faced in the Bayesian analysis of statistical problems. The implementation of MCMC algorithms is, however, code intensive and time consuming. We have developed a Python package, which is called PyMCMC, that aids in the construction of MCMC samplers and helps to substantially reduce the likelihood of coding error, as well as aid in the minimisation of repetitive code. PyMCMC contains classes for Gibbs, Metropolis Hastings, independent Metropolis Hastings, random walk Metropolis Hastings, orientational bias Monte Carlo and slice samplers as well as specific modules for common models such as a module for Bayesian regression analysis. PyMCMC is straightforward to optimise, taking advantage of the Python libraries Numpy and Scipy, as well as being readily extensible with C or Fortran.

Assessment of pre- and post-flood groundwater recharge via 3D visualisation, Lockyer Valley, southeast Queensland

The Lockyer Valley in southeast Queensland supports important and intensive irrigation which is dependant on the quality and availability of groundwater. Prolonged drought conditions from ~1997 resulted in a depletion of the alluvial aquifers, and concern for the long-term sustainability of this resource. By 2008, many areas of the valley were at < 20% of storage. Some relief occurred with rain events in early 2009, then in December 2010 - January 2011, most of southeast Queensland experienced unprecedented flooding. These storm-based events have caused a shift in research focus from investigations of drought conditions and mitigation to flood response analysis. For the alluvial aquifer system of the valley, a preliminary assessment of groundwater observation bore data, prior to and during the flood, indicates that there is a spatially variable aquifer response. While water levels in some bores screened in unconfined shallow aquifers have recovered by more than 10 m within a short period of time (months), others show only a small or moderate response. Measurements of pre- and post-flood groundwater levels and high-resolution time-series records from data loggers are considered within the framework of a 3D geological model of the Lockyer Valley using Groundwater Visualisation System(GVS). Groundwater level fluctuations covering both drought and flood periods are used to estimate groundwater recharge using the water table fluctuation method (WTF), supplemented by estimates derived using chloride mass balance. The presentation of hydraulic and recharge information in a 3D format has considerable advantages over the traditional 2D presentation of data. The 3D approach allows the distillation of multiple types of information(topography, geological, hydraulic and spatial) into one representation that provides valuable insights into the major controls of groundwater flow and recharge. The influence of aquifer lithology on the spatial variability of groundwater recharge is also demonstrated.

Walking with another : rural nurses' experiences of mentoring

The aim of this constructivist grounded theory study was to explore rural nurses' experiences of mentoring. Mentoring is often proposed as a solution to the problem of nursing workforce shortages. The global problem of workforce for nurses can be defined using the parameters of recruitment and retention rates, 'problems' with which result in staff shortages, particularly of experienced nurses. Constructivist grounded theory has its foundations in relativism and an appreciation of the multiple truths and realities of subjectivism. Seven Australian rural nurses were interviewed. To ensure data saturation of particular categories and the fit of tentative theoretical conceptualisations, two participants were interviewed twice with no new codes identified from the subsequent interviews. Cultivating and growing new or novice rural nurses was the core category which conceptualised a two-part process consisting of getting to know a stranger and walking with another. Supportive relationships such as mentoring were found to be an existing, integral part of experienced rural nurses' practice - initiated by living and working in the same community. In this grounded theory, cultivating and growing is conceptualised as the core category. A two-part process was identified - getting to know a stranger and walking with another. This paper examines one of these subcategories, walking with another, relating the ways in which experienced rural nurses walk with another by firstly keeping things in perspective for new or novice rural nurses, and secondly using a particular form of language called nurse chat. For experienced rural nurses, mentoring in this way delivers a number of different outcomes with various nurses. Because it is a part of the experienced rural nurse's practice on an ongoing basis, individual mentoring relationships do not provide an end in relation to this nurse's experiences of mentoring, rather they are part of an ongoing experience. Creating supportive environments that include developing relationships such as mentoring is a potential solution to local staffing needs that does not require intensive resources. Experienced nurses engaged in clinical practice have the potential to cultivate and grow new or novice nurses - many already do so. Recognising their role and providing support as well as development opportunities will bring about a cycle of mentoring within the workplace. © 2008 Sage Publications.

Defending web services against denial of service attacks using client puzzles

The interoperable and loosely-coupled web services architecture, while beneficial, can be resource-intensive, and is thus susceptible to denial of service (DoS) attacks in which an attacker can use a relatively insignificant amount of resources to exhaust the computational resources of a web service. We investigate the effectiveness of defending web services from DoS attacks using client puzzles, a cryptographic countermeasure which provides a form of gradual authentication by requiring the client to solve some computationally difficult problems before access is granted. In particular, we describe a mechanism for integrating a hash-based puzzle into existing web services frameworks and analyze the effectiveness of the countermeasure using a variety of scenarios on a network testbed. Client puzzles are an effective defence against flooding attacks. They can also mitigate certain types of semantic-based attacks, although they may not be the optimal solution.

CDA and values : interdisciplinarity as a critical turn

From their very outset, the disciplines of social science have claimed a need for interdisciplinarity. Proponents of new disciplines have also claimed the whole of human activity as their domain, whilst simultaneously emphasising the need for increased specialisation. Critical social analysis attempts to repair the flaws of specialisation. In this chapter, I argue that the trend towards academic specialisation in social science is most usefully viewed from the perspective of evaluative meaning, and that each new discipline, in emphasising one aspect of a broken conception of humanity, necessarily emphasises one aspect of an already broken conception of value. Critical discourse analysis, qua critical social analysis, may therefore benefit by firstly proceeding from the perspective of evaluative meaning to understand the dynamics of social change and overcome the challenges posed by centuries of intensive specialisation in social science.

Are low CO2 emitters in rural areas also socially excluded? An empirical investigation of travel diary data from rural Northern Ireland

The reduction of CO2 emissions and social exclusion are two key elements of UK transport strategy. Despite intensive research on each theme, little effort has so far been made linking the relationship between emissions and social exclusion. In addition, current knowledge on each theme is limited to urban areas; little research is available on these themes for rural areas. This research contributes to this gap in the literature by analysing 157 weekly activity-travel diary data collected from three case study areas with differential levels of area accessibility and area mobility options, located in rural Northern Ireland. Individual weekly CO2 emission levels from personal travel diaries (both hot exhaust emission and cold-start emission) were calculated using average speed models for different modes of transport. The socio-spatial patterns associated with CO2 emissions were identified using a general linear model whereas binary logistic regression analyses were conducted to identify mode choice behaviour and activity patterns. This research found groups that emitted a significantly lower level of CO2 included individuals living in an area with a higher level of accessibility and mobility, non-car, non-working, and low-income older people. However, evidence in this research also shows that although certain groups (e.g. those working, and residing in an area with a lower level of accessibility) emitted higher levels of CO2, their rate of participation in activities was however found to be significantly lower compared to their counterparts. Based on the study findings, this research highlights the need for both soft (e.g. teleworking) and physical (e.g. accessibility planning) policy measures in rural areas in order to meet government’s stated CO2 reduction targets while at the same time enhancing social inclusion.

Understanding intraaortic balloon pumping

Intraaortic balloon pumping (IABP) is an established treatment for the support of a failing heart (Christenson, Simonet et al. 1997). It is a process undertaken in most level two and three intensive care units. Despite IABP appearing complex, the principles are straightforward. A sausage shaped intraaortic balloon (IAB) about 250 millimetres long and 15 millimetres in diameter, is placed in the descending aorta and attached to an external pump. The external pump then inflates and deflates the IAB in synchrony with cardiac contraction. The primary purpose of this is the support of a compromised heart with a simultaneous increase in myocardial oxygen supply, and decrease in myocardial oxygen demand (Overwalder, 1999). As a nurse it is worthwhile understanding the principles of IABP. As a hospital intervention, it’s exposure to nursing is high.