Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes

Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.

An outcome evaluation of the ‘Skipper’ designated driver program

The general aim of designated driver programs is to reduce the level of drink driving by encouraging potential drink drivers to travel with a driver who has abstained from (or at least limited) consuming alcohol. Designated driver programs appear to be quite widespread around the world, however a limited number have been subject to rigorous evaluation. This paper reports results from an outcome evaluation of a designated driver program called ‘Skipper’, which was trialled in a provincial city in Queensland, Australia. The outcome evaluation included surveys three weeks prior to (baseline), four months following (1st follow-up), and 16 months following (2nd follow-up) the commencement of the trial in both the ‘intervention area’ (baseline, n = 202; 1st follow-up, n = 211; 2nd follow-up, n = 200) and a ‘comparison area’(baseline, n = 203; 1st follow-up, n = 199; 2nd follow-up, n = 201); and a comparison of random breath testing and crash data before and after the trial. The survey results indicate that awareness of the program in the intervention area was quite high four months following its introduction and that this was maintained at 16 months. The results also suggest that the ‘Skipper’ program and the related publicity had positive impacts on behaviour with an increase in the proportion of people participating in designated driver as a passenger. It is less clear, however, whether the ‘Skipper’ program impacted on other behaviours of interest, such as drink driving or involvement in alcohol-related crashes. Suggestions for further research and program improvement are discussed as well as limitations of the research.

When leadership meets organizational change : the influence of the top management team and supervisory leaders on change appraisals, change attitudes, and adjustment to change

Despite the importance of adaption and change for firm survival, the failure rate of organizational change efforts remains alarmingly high (Beer and Nohria, 2000; Kotter, 1995). In a recent global survey of over 3,000 executives,Meaney and Pung (2008) reported that two-thirds of executives indicated that their firm had failed to successfully implement organizational changes. Similarly, academic researchers have also concluded that difficulties in implementing and managing organizational change efforts often precipitate organizational crises (Probst and Raisch, 2005). As a result, attention has been directed to identify the factors that improve the likelihood of successfully implementing organizational change efforts. While there has been practitioner-oriented discussion around the pivotal role of workplace leaders in reducing resistance to change, only a limited number of empirical studies have examined relationships between leader behavior and employee change attitudes (e.g., Bommer, Rich, and Rubin, 2005; Herold, Caldwell, and Liu, 2008; Nemanich and Keller, 2007; Oreg and Berson, 2011). However...

A disaggregate discrete choice model of transportation demand by elderly and disabled people in rural Virginia

This paper uses a correlated multinomial logit model and a Poisson regression model to measure the factors affecting demand for different types of transportation by elderly and disabled people in rural Virginia. The major results are: (a) A paratransit system providing door-to-door service is highly valued by transportation-handicapped people; (b) Taxis are probably a potential but inferior alternative even when subsidized; (c) Buses are a poor alternative, especially in rural areas where distances to bus stops may be long; (d) Making buses handicap-accessible would have a statistically significant but small effect on mode choice; (e) Demand is price inelastic; and (f) The total number of trips taken is insensitive to mode availability and characteristics. These results suggest that transportation-handicapped people take a limited number of trips. Those they do take are in some sense necessary (given the low elasticity with respect to mode price or availability). People will substitute away from relying upon others when appropriate transportation is available, at least to some degree. But such transportation needs to be flexible enough to meet the needs of the people involved.

The Australian general public's perceptions of having a personally controlled electronic health record (PCEHR)

Objective The move internationally by Governments and other health providers to encourage patients to have their own electronic personal health record (e-PHRs) is growing exponentially. In Australia the initiative for a personally controlled electronic health record (known as PCEHR) is directed towards the public at large. The first objective of this study then, is to examine how individuals in the general population perceive the promoted idea of having a PCEHR. The second objective is to extend research on applying a theoretically derived consumer technology acceptance model to guide the research. Method An online survey was conducted to capture the perceptions and beliefs about having a PCEHR identified from technology acceptance models and extant literature. The survey was completed by 750 Queensland respondents, 97% of whom did not have a PCEHR at that time. The model was examined using exploratory factor analysis, regressions and mediation tests. Results Findings support eight of the 11 hypothesised relationships in the model. Perceived value and perceived risk were the two most important variables explaining attitude, with perceived usefulness and compatibility being weak but significant. The perception of risk was reduced through partial mediation from trust and privacy concerns. Additionally, web-self efficacy and ease of use partially mediate the relationship between attitude and intentions. Conclusions The findings represent a snapshot of the early stages of implementing this Australian initiative and captures the perceptions of Queenslanders who at present do not have a PCEHR. Findings show that while individuals appreciate the value of having this record, they do not appear to regard it as particularly useful at present, nor is it particularly compatible with their current engagement with e-services. Moreover, they will need to have any concerns about the risks alleviated, particularly through an increased sense of trust and reduction of privacy concerns. It is noted that although the respondents are non-adopters, they do not feel that they lack the necessary web skills to set up and use a PCEHR. To the best of our knowledge this is one of a very limited number of studies that examines a national level implementation of an e-PHR system, where take-up of the PCEHR is optional rather than a centralised, mandated requirement.

Experimental evidence for competitive N–O and O–C bond homolysis in gasphase alkoxyamines

The extensive use of alkoxyamines in controlled radical polymerisation and polymer stabilisation is based on rapid cycling between the alkoxyamine (R1R2NO–R3) and a stable nitroxyl radical (R1R2NO•) via homolysis of the labile O–C bond. Competing homolysis of the alkoxyamine N–O bond has been predicted to occur for some substituents leading to production of aminyl and alkoxyl radicals. This intrinsic competition between the O–C and N–O bond homolysis processes has to this point been difficult to probe experimentally. Herein we examine the effect of local molecular structure on the competition between N–O and O–C bond cleavage in the gas phase by variable energy tandem mass spectrometry in a triple quadrupole mass spectrometer. A suite of cyclic alkoxyamines with remote carboxylic acid moieties (HOOC–R1R2NO–R3) were synthesised and subjected to negative ion electrospray ionisation to yield [M – H]− anions where the charge is remote from the alkoxyamine moiety. Collision-induced dissociation of these anions yield product ions resulting, almost exclusively, from homolysis of O–C and/or N–O bonds. The relative efficacy of N–O and O–C bond homolysis was examined for alkoxyamines incorporating different R3 substituents by varying the potential difference applied to the collision cell, and comparing dissociation thresholds of each product ion channel. For most R3 substituents, product ions from homolysis of the O–C bond are observed and product ions resulting from cleavage of the N–O bond are minor or absent. A limited number of examples were encountered however, where N–O homolysis is a competitive dissociation pathway because the O–C bond is stabilised by adjacent heteroatom(s) (e.g., R3 = CH2F). The dissociation threshold energies were compared for different alkoxyamine substituents (R3) and the relative ordering of these experimentally determined energies is shown to correlate with the bond dissociation free energies, calculated by ab initio methods. Understanding the structure-dependent relationship between these rival processes will assist in the design and selection of alkoxyamine motifs that selectively promote the desirable O–C homolysis pathway.

Assessing the bilateral geometrical differences of the tibia : are they the same?

Contralateral bones are often used in many medical applications but it is assumed that their bilateral differences are insignificant. Previous studies used a limited number of distance measurements in quantifying the corresponding differences; therefore, little is known about their bilateral 3D surface asymmetries. The aim of the study is to develop a comprehensive method to quantify geometrical asymmetries between the left and right tibia in order to provide first results on whether the contralateral tibia can be used as an equivalent reference. In this study, 3D bone models were reconstructed from CT scans of seven tibiae pairs, and 34 variables consisting of 2D and 3D measurements were measured from various anatomical regions. All 2D measurements, and lateral plateau and distal subchondral bone surface measurements showed insignificant differences (p > 0.05), but the rest of the surfaces showed significant differences (p < 0.05). Our results suggest that the contralateral tibia can be used as a reference especially in surgical applications such as articular reconstructions since the bilateral differences in the subchondral bone surfaces were less than 0.3 mm. The method can also be potentially transferable to other relevant studies that require the accurate quantification of bone bilateral asymmetries.

Conclusion

This monograph provides an overview of recruitment learning approaches from a computational perspective. Recruitment learning is a unique machine learning technique that: (1) explains the physical or functional acquisition of new neurons in sparsely connected networks as a biologically plausible neural network method; (2) facilitates the acquisition of new knowledge to build and extend knowledge bases and ontologies as an artificial intelligence technique; (3) allows learning by use of background knowledge and a limited number of observations, consistent with psychological theory.

Optimising ketocarotenoid production in potato tubers : effect of genetic background, transgene combinations and environment

Astaxanthin is a high value carotenoid produced by some bacteria, a few green algae, several fungi but only a limited number of plants from the genus Adonis. Astaxanthin has been industrially exploited as a feed supplement in poultry farming and aquaculture. Consumption of ketocarotenoids, most notably astaxanthin, is also increasingly associated with a wide range of health benefits,as demonstrated in numerous clinical studies. Currently astaxanthin is produced commercially by chemical synthesis or from algal production systems. Several studies have used a metabolic engineering approach to produce astaxanthin in transgenic plants. Previous attempts to produce transgenic potato tubers biofortified with astaxanthin have met with limited success. In this study we have investigated approaches to optimising tuber astaxanthin content. It is demonstrated that the selection of appropriate parental genotype for transgenic approaches and stacking carotenoid biosynthetic pathway genes with the cauliflower Or gene result in enhanced astaxanthin content, to give six-fold higher tuber astaxanthin content than has been achieved previously. Additionally we demonstrate the effects of growth environment on tuber carotenoid content in both wild type and astaxanthin-producing transgenic lines and describe the associated transcriptome and metabolome restructuring.

Role of rainfall and catchment characteristics on urban stormwater quality

Urbanisation significantly changes the characteristics of a catchment as natural areas are transformed to impervious surfaces such as roads, roofs and parking lots. The increased fraction of impervious surfaces leads to changes to the stormwater runoff characteristics, whilst a variety of anthropogenic activities common to urban areas generate a range of pollutants such as nutrients, solids and organic matter. These pollutants accumulate on catchment surfaces and are removed and trans- ported by stormwater runoff and thereby contribute pollutant loads to receiving waters. In summary, urbanisation influences the stormwater characteristics of a catchment, including hydrology and water quality. Due to the growing recognition that stormwater pollution is a significant environmental problem, the implementation of mitigation strategies to improve the quality of stormwater runoff is becoming increasingly common in urban areas. A scientifically robust stormwater quality treatment strategy is an essential requirement for effective urban stormwater management. The efficient design of treatment systems is closely dependent on the state of knowledge in relation to the primary factors influencing stormwater quality. In this regard, stormwater modelling outcomes provide designers with important guidance and datasets which significantly underpin the design of effective stormwater treatment systems. Therefore, the accuracy of modelling approaches and the reliability modelling outcomes are of particular concern. This book discusses the inherent complexity and key characteristics in the areas of urban hydrology and stormwater quality, based on the influence exerted by a range of rainfall and catchment characteristics. A comprehensive field sampling and testing programme in relation to pollutant build-up, an urban catchment monitoring programme in relation to stormwater quality and the outcomes from advanced statistical analyses provided the platform for the knowledge creation. Two case studies and two real-world applications are discussed to illustrate the translation of the knowledge created to practical use in relation to the role of rainfall and catchment characteristics on urban stormwater quality. An innovative rainfall classification based on stormwater quality was developed to support the effective and scientifically robust design of stormwater treatment systems. Underpinned by the rainfall classification methodology, a reliable approach for design rainfall selection is proposed in order to optimise stormwater treatment based on both, stormwater quality and quantity. This is a paradigm shift from the common approach where stormwater treatment systems are designed based solely on stormwater quantity data. Additionally, how pollutant build-up and stormwater runoff quality vary with a range of catchment characteristics was also investigated. Based on the study out- comes, it can be concluded that the use of only a limited number of catchment parameters such as land use and impervious surface percentage, as it is the case in current modelling approaches, could result in appreciable error in water quality estimation. Influential factors which should be incorporated into modelling in relation to catchment characteristics, should also include urban form and impervious surface area distribution. The knowledge created through the research investigations discussed in this monograph is expected to make a significant contribution to engineering practice such as hydrologic and stormwater quality modelling, stormwater treatment design and urban planning, as the study outcomes provide practical approaches and recommendations for urban stormwater quality enhancement. Furthermore, this monograph also demonstrates how fundamental knowledge of stormwater quality processes can be translated to provide guidance on engineering practice, the comprehensive application of multivariate data analyses techniques and a paradigm on integrative use of computer models and mathematical models to derive practical outcomes.

Fear of falling in vision impairment

Falls are the leading cause of injury-related morbidity and mortality among older adults. In addition to the resulting physical injury and potential disability after a fall, there are also important psychological consequences, including depression, anxiety, activity restriction, and fear of falling. Fear of falling affects 20 to 43% of community-dwelling older adults and is not limited to those who have previously experienced a fall. About half of older adults who experience fear of falling subsequently restrict their physical and everyday activities, which can lead to functional decline, depression, increased falls risk, and reduced quality of life. Although there is clear evidence that older adults with visual impairment have higher falls risk, only a limited number of studies have investigated fear of falling in older adults with visual impairment and the findings have been mixed. Recent studies suggest increased levels of fear of falling among older adults with various eye conditions, including glaucoma and age-related macular degeneration, whereas other studies have failed to find differences. Interventions, which are still in their infancy in the general population, are also largely unexplored in those with visual impairment. The major aims of this review were to provide an overview of the literature on fear of falling, its measurement, and risk factors among older populations, with specific focus on older adults with visual impairment, and to identify directions for future research in this area.

Ultrafine particle emission of waste incinerators and comparison to the exposure of urban citizens

On the basis of the growing interest on the impact of airborne particles on human exposure as well as the strong debate in Western countries on the emissions of waste incinerators, this work reviewed existing literature to: (i) show the emission factors of ultrafine particles (particles with a diameter less than 100 nm) of waste incinerators, and; (ii) assess the contribution of waste incinerators in terms of ultrafine particles to exposure and dose of people living in the surrounding areas of the plants in order to estimate eventual risks. The review identified only a limited number of studies measuring ultrafine particle emissions, and in general they report low particle number concentrations at the stack (the median value was equal to 5.5×103 part cm-3), in most cases higher than the outdoor background value. The lowest emissions were achieved by utilization of the bag-house filter which has an overall number-based filtration efficiency higher than 99%. Referring to reference case, the corresponding emission factor is equal to 9.1×1012 part min-1, that is lower than one single high-duty vehicle. Since the higher particle number concentrations found in the most contributing microenvironments to the exposure (indoor home, transportation, urban outdoor), the contribution of the waste incinerators to the daily dose can be considered as negligible.

DoGood : A gamified mobile app to promote civic engagement

The rise of the mobile Internet enables the creation of applications that provide new and easier ways for people to organise themselves, raise issues, take action and interact with their city. However, a lack of motivation or knowledge often prevents many citizens from regularly contributing to the common good. Therefore, this thesis presents DoGood, a smartphone app, that aims at motivating citizens to carry out civic activities. The thesis asks what kinds of activities citizens consider to be civic and to what extent gamification can motivate users in this context. The DoGood app uses gamified elements to encourage citizens to submit and promote their civic activities as well as to join the activities of others. Gamification is sometimes criticized for simply adding a limited number of game elements, such as leaderboards, on top of an existing experience. However, in the case of the DoGood app, the process of game design was an integral part of the development, and the gamified elements target the user’s intrinsic motivations instead of providing them with an external reward. DoGood was implemented as hybrid mobile app and deployed to citizens of Brisbane in a five weeks long user study. The app successfully motivated most of its users to do more civic activities and its gamified elements were well received. Based on the results of the user study, civic activities can be defined as activities that give citizens the opportunity to become involved and improve life in their local community.

Gamifying collective intelligence for the common good

The rise of the mobile internet enables the creation of applications that provide new and easier ways for people to organise themselves, raise issues, take action and interact with their city. At the same time, society faces new problems that can only be solved when citizens work together. Nevertheless, a lack of motivation or knowledge often prevents many citizens from regularly contributing to the common good. In this position paper, we present DoGood – a mobile app – as a socio-technological system that aims at supporting the collective intelligence of citizens in their pursuit of civic engagement and civic collaboratories. Our study asks to what extent gamification can motivate users to “do good” deeds. The DoGood app uses gamified elements to encourage citizens to submit and promote their civic activities as well as to join the activities of others. Gamification is sometimes criticised for simply adding a limited number of game elements, such as leaderboards, on top of an existing experience with the hope of increasing motivation. However, in the case of the DoGood app, the process of game design was an integral part of the development, and the gamified elements target the user’s intrinsic motivations instead of providing them with an external reward. In this paper, we present design elements of the app and discuss their potential to support collective intelligence for the common good.

The short-term accommodation response to aniso-accommodative stimuli in isometropia

Purpose There have been only a limited number of studies examining the accommodative response that occurs when the two eyes are provided with disparate accommodative stimuli, and the results from these studies to date have been equivocal. In this study, we therefore aimed to examine the capacity of the visual system to aniso-accommodate by objectively measuring the interocular difference in the accommodation response between fellow dominant and non-dominant eyes under controlled monocular and binocular viewing conditions during short-term exposure to aniso-accommodative stimuli. Methods The accommodative response of each eye of sixteen young isometropic adults (mean age 22 ± 2 years) with normal binocular vision was measured using an open-field autorefractor during a range of testing conditions; monocularly (accommodative demands ranging from 1.32 to 4.55 D) and binocularly while altering the accommodation demand for each eye (aniso-accommodative stimuli ranging from 0.24 to 2.05 D). Results Under monocular viewing conditions, the dominant and non-dominant eyes displayed a highly symmetric accommodative response; mean interocular difference in spherical equivalent 0.01 ± 0.06 D (relative) and 0.22 ± 0.06 D (absolute) (p>0.05). During binocular viewing, the dominant eye displayed a greater accommodative response (0.11 ± 0.34 D relative and 0.24 ± 0.26 D absolute) irrespective of whether the demand of the dominant or non-dominant eye was altered (p = 0.01). Astigmatic power vectors J0 and J45 did not vary between eyes or with increasing accommodation demands under monocular or binocular viewing conditions (p>0.05). Conclusion The dominant and non-dominant eyes of young isometropic individuals display a similar consensual lag of accommodation under both monocular and binocular viewing conditions, with the dominant eye showing a small but significantly greater (by 0.12 to 0.25 D) accommodative response. Evidence of short-term aniso-accommodation in response to asymmetric accommodation demands was not observed.