INVESTIGATING THE ROLE OF NOX NADPH OXIDASE SIGNALLING IN CELL MIGRATION AND ANGIOGENESIS OF ENDOTHELIAL COLONY-FORMING CELLS

Introduction. Endothelial colony-forming cells (ECFCs) hold great cytotherapeutic potential for ischaemic disease. Emerging evidence supports a key role for NADPH oxidases in underlying angiogenic processes of these and other endothelial cells. Aims. To study the influence of Nox NADPH oxidases on the pro-angiogenic function of ECFCs. Methods. Human ECFCs isolated from umbilical cord blood were treated with pro-oxidant PMA and assessed in vitro, both under basal conditions and after siRNA knockdown of Nox4, a key endothelial NADPH oxidase isoform, alongside primary mature human aortic endothelial cells (HAoECs) for comparison, using an established scratch-wound assay as the functional end-point. Results. PMA (500nM for 8h) increased cell migration (control 18.6±2.8, PMA 32.7±6.6% wound closure; n=6, P<0.05) in a superoxide-dependent manner, as indicated by attenuation of this effect in the presence of PEG-SOD. Although HAoEC migration in response to PMA also tended to increase, this did not reach statistical significance. Notably, cell migration at 16h was reduced by Nox4 knockdown in ECFCs (control siRNA 53.4±3.5, Nox4 siRNA 35.1±4.9% closure; n=3, P<0.05), but not in HAoECs, whilst the pro-migratory effect of PMA in ECFCs was potentiated after Nox4 knockdown (control siRNA 53.4±3.5, +PMA 61.5±3.2% closure; n=3, P=NS; Nox4 siRNA 35.1±4.9, +PMA 53.0±4.9% closure; n=3, P<0.05). Conclusion. ECFC migration is enhanced by low concentrations of superoxide, to a greater extent compared to mature endothelial cells, and appears to be at least partly dependent upon NADPH oxidase, including a specific role for Nox4. Although, the precise contribution of endothelial Nox NADPH oxidases isoforms remains to be determined, it is clear that these findings may have significant implications for potential ECFC-based therapies for ischaemic disease, which is associated with an oxidative microenvironment.

From 'trailing wives' to the emergence of a 'trailing husbands' phenomenon: Retirement migration to rural areas

Migration and gender studies have focused on economically active heterogeneous couples and traditionally highlight a dominant male role in migration decision-making. The female partner is commonly portrayed as a 'trailing wife' or 'trailing mother' with the move found to have a negative effect on her employment prospects. Much less is known about if or how the balance of power shifts between husbands and wives when employment or career-motivated moves are removed from the decision-making process. This is analysed with reference to retirement migration to rural areas of the UK and involved interviews with both partners present. For this cohort of retired couples, and in common with the literature, migration during economically active life course stages demonstrates strong 'trailing wife' and 'trailing mother' tendencies. The male's decision to retire signalled the commencement of a retirement life course stage for the couple. However, in contrast to the earlier male dominated decision-making, retirement migration saw the emergence of a 'trailing husband' phenomenon. Wives appear to adapt most successfully to the new rural environment while many husbands found it difficult to adjust (at least initially) to the multiple life changes: moving from largely urban areas to a rural setting alongside exiting the workforce. The findings suggest that the role of leader/ follower changed during the course of these couples' lives together and in relation to their reasons for moving.

Is Longer-Distance Migration Slowing? An Analysis of the Annual Record for England and Wales since the 1970s

This paper is prompted by the widespread acceptance that the rates of inter-county and inter-state migration have been falling in the USA and sets itself the task of examining whether this decline in migration intensities is also the case in the UK. It uses annual inter-area migration matrices available for England and Wales since the 1970s by broad age group. The main methodological challenge, arising from changes in the geography of health areas for which the inter-area flows are given, is addressed by adopting the lowest common denominator of 80 areas. Care is also taken to allow for the effect of economic cycles in producing short-term fluctuations on migration rates and to isolate the effect of a sharp rise in rates for 16-24 year olds in the 1990s, which is presumed to be related to the expansion of higher education. The findings suggest that, unlike for the USA, there has not been a substantial decline in the intensity of internal migration between the first two decades of the study period and the second two. If there has been any major decline in the intensity of address changing in England and Wales, it can only be for the within-area moves that this time series does not cover. This latter possibility is examined in a companion paper using a very different data set (Champion and Shuttleworth, 2016).

Are People Changing Address Less? An Analysis of Migration within England and Wales, 1971–2011, by Distance of Move

Expectations of migration and mobility steadily increasing in the longer term, which have a long currency in migration theory and related social science, are at odds with the latest US research showing a marked decline in internal migration rates. This paper reports the results of research that investigates whether England and Wales have experienced any similar change in recent decades. Using the Office for National Statistics Longitudinal Study (ONS-LS) of linked census records, it examines the evidence provided by its 10-year migration indicator, with particular attention to a comparison of the first and latest decades available, 1971-1981 and 2001-2011. This suggests that, as in the USA, there has been a marked reduction in the level of shorter-distance (less than 10km) moving that has involved almost all types of people. In contrast to this and to US experience, however, the propensity of people to make longer-distance address changes between decennial censuses has declined much less, largely corroborating the results of a companion study tracking the annual trend in rates of between-area migration since the 1970s (Champion and Shuttleworth, 2016).

A high-value, low-cost bubble continuous positive airway pressure system for low-resource settings:technical assessment and initial case reports

Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple design--consumer-grade pumps, medical tubing, and regulators--it requires only the simple replacement of a <$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device.