Active Notch1 confers a transformed phenotype to primary human melanocytes

The importance of mitogen-activated protein kinase signaling in melanoma is underscored by the prevalence of activating mutations in N-Ras and B-Raf, yet clinical development of inhibitors of this pathway has been largely ineffective, suggesting that alternative oncogenes may also promote melanoma. Notch is an interesting candidate that has only been correlated with melanoma development and progression; a thorough assessment of tumor-initiating effects of activated Notch on human melanocytes would clarify the mounting correlative evidence and perhaps identify a novel target for an otherwise untreatable disease. Analysis of a substantial panel of cell lines and patient lesions showed that Notch activity is significantly higher in melanomas than their nontransformed counterparts. The use of a constitutively active, truncated Notch transgene construct (N(IC)) was exploited to determine if Notch activation is a "driving" event in melanocytic transformation or instead a "passenger" event associated with melanoma progression. N(IC)-infected melanocytes displayed increased proliferative capacity and biological features more reminiscent of melanoma, such as dysregulated cell adhesion and migration. Gene expression analyses supported these observations and aided in the identification of MCAM, an adhesion molecule associated with acquisition of the malignant phenotype, as a direct target of Notch transactivation. N(IC)-positive melanocytes grew at clonal density, proliferated in limiting media conditions, and also exhibited anchorage-independent growth, suggesting that Notch alone is a transforming oncogene in human melanocytes, a phenomenon not previously described for any melanoma oncogene. This new information yields valuable insight into the basic epidemiology of melanoma and launches a realm of possibilities for drug intervention in this deadly disease.

Intelligent computing and sensing for active safety on construction sites

On obstacle-cluttered construction sites where heavy equipment is in use, safety issues are of major concern. The main objective of this paper is to develop a framework with algorithms for obstacle avoidance and path planning based on real-time three-dimensional job site models to improve safety during equipment operation. These algorithms have the potential to prevent collisions between heavy equipment vehicles and other on-site objects. In this study, algorithms were developed for image data acquisition, real-time 3D spatial modeling, obstacle avoidance, and shortest path finding and were all integrated to construct a comprehensive collision-free path. Preliminary research results show that the proposed approach is feasible and has the potential to be used as an active safety feature for heavy equipment.

Identifying parent perspectives to guide active travel intervention with small populations : case study in Denver, Colorado

This paper investigates a strategy for guiding school-based active travel intervention. School-based active travel programs address the travel behaviors and perceptions of small target populations (i.e., at individual schools) so they can encourage people to walk or bike. Thus, planners need to know as much as possible about the behaviors and perceptions of their target populations. However, existing strategies for modeling travel behavior and segmenting audiences typically work with larger populations and may not capture the attitudinal diversity of smaller groups. This case study used Q technique to identify salient travel-related attitude types among parents at an elementary school in Denver, Colorado; 161 parents presented their perspectives about school travel by rank-ordering 36 statements from strongly disagree to strongly agree in a normalized distribution, single centered around no opinion. Thirty-nine respondents' cases were selected for case-wise cluster analysis in SPSS according to criteria that made them most likely to walk: proximity to school, grade, and bus service. Analysis revealed five core perspectives that were then correlated with the larger respondent pool: optimistic walkers, fair-weather walkers, drivers of necessity, determined drivers, and fence sitters. Core perspectives are presented—characterized by parents' opinions, personal characteristics, and reported travel behaviors—and recommendations are made for possible intervention approaches. The study concludes that Q technique provides a fine-grained assessment of travel behavior for small populations, which would benefit small-scale behavioral interventions

Service providers' perceptions of active ageing among older adults with lifelong intellectual disabilities

Background: Considerable attention is currently being directed towards both active ageing and the revising of standards for disability services within Australia and internationally. Yet, to date, no consideration appears to have been given to ways to promote active ageing among older adults with intellectual disabilities. Methods: Semi-structured interviews were conducted with 16 Australian professional direct-care support staff (service providers) about their perceptions of ageing among older adults with lifelong intellectual disabilities and what active ageing might entail for an individual from this population who is currently under their care, in both the present and future. Data were analysed against the six core World Health Organization active ageing outcomes for people with intellectual disabilities. Results: Service providers appeared to be strongly focused on encouraging active ageing among their clients. However, their perceptions of the individual characteristics, circumstances and experiences of older adults with intellectual disabilities for whom they care suggest that active ageing principles need to be applied to this group in a way that considers both their individual and diverse needs, particularly with respect to them transitioning from day services, employment or voluntary work to reduced activity, and finally to aged care facilities. The appropriateness of this group being placed in nursing homes in old age was also questioned. Conclusion: Direct-care staff of older adults with intellectual disabilities have a vital role to play in encouraging and facilitating active ageing, as well as informing strategies that need to be implemented to ensure appropriate care for this diverse group as they proceed to old age.

A human factors investigation into the unavailability of active warnings at railway level crossings

This paper discusses human factors issues of low cost railway level crossings in Australia. Several issues are discussed in this paper including safety at passive level railway crossings, human factors considerations associated with unavailability of a warning device, and a conceptual model for how safety could be compromised at railway level crossings following prolonged or frequent unavailability. The research plans to quantify safety risk to motorists at level crossings using a Human Reliability Assessment (HRA) method, supported by data collected using an advanced driving simulator. This method aims to identify human error within tasks and task units identified as part of the task analysis process. It is anticipated that by modelling driver behaviour the current study will be able to quantify meaningful task variability including temporal parameters, between participants and within participants. The process of complex tasks such as driving through a level crossing is fundamentally context-bound. Therefore this study also aims to quantify those performance-shaping factors that contribute to vehicle train collisions by highlighting changes in the task units and driver physiology. Finally we will also consider a number of variables germane to ensuring external validity of our results. Without this inclusion, such an analysis could seriously underestimate risk.

Active ageing : developing a quantitative multi-dimensional measure

With estimates that two billion of the world’s population will be 65 years or older by 2050, ensuring that older people ‘age well’ is an international priority. To date, however, there is significant disagreement and debate about how to define and measure ‘ageing well’, with no consensus on either terminology or measurement. Thus, this chapter describes the research rationale, methodology and findings of the Australian Active Ageing Study (Triple A Study), which surveyed 2620 older Australians to identify significant contributions to quality of life for older people: work, learning, social participation, spirituality, emotional wellbeing, health, and life events. Exploratory factor analyses identified eight distinct elements (grouped into four key concepts) which appear to define ‘active ageing’ and explained 55% of the variance: social and life participation (25%), emotional health (22%), physical health and functioning (4%) and security (4%). These findings highlight the importance of understanding and supporting the social and emotional dimensions of ageing, as issues of social relationships, life engagement and emotional health dominated the factor structure. Our intension is that this paper will prompt informed debate and discussion on defining and measuring active ageing, facilitating exploration and understanding of the complexity of issues that intertwine, converge and enhance the ageing experience.

From barrier elimination to barrier negotiation : a qualitative study of parents' attitudes about active travel for elementary school trips

This paper examines parents' responses to key factors associated with mode choices for school trips. The research was conducted with parents of elementary school students in Denver Colorado as part of a larger investigation of school travel. School-based active travel programs aim to encourage students to walk or bike to school more frequently. To that end, planning research has identified an array of factors associated with parents' decisions to drive children to school. Many findings are interpreted as ‘barriers’ to active travel, implying that parents have similar objectives with respect to travel mode choices and that parents respond similarly and consistently to external conditions. While the conclusions are appropriate in forecasting demand and mode share with large populations, they are generally too coarse for programs that aim to influence travel behavior with individuals and small groups. This research uses content analysis of interview transcripts to examine the contexts of factors associated with parents' mode choices for trips to and from elementary school. Short, semi-structured interviews were conducted with 65 parents from 12 Denver Public Elementary Schools that had been selected to receive 2007–08 Safe Routes to School non-infrastructure grants. Transcripts were analyzed using Nvivo 8.0 to find out how parents respond to selected factors that are often described in planning literature as ‘barriers’ to active travel. Two contrasting themes emerged from the analysis: barrier elimination and barrier negotiation. Regular active travel appears to diminish parents' perceptions of barriers so that negotiation becomes second nature. Findings from this study suggest that intervention should build capacity and inclination in order to increase rates of active travel.

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers : a potential marker of physical activity

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic / anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3 / endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk / survival.

Active regulation of the epidermal calcium profile

A distinct calcium profile is strongly implicated in regulating the multi-layered structure of the epidermis. However, the mechanisms that govern the regulation of this calcium profile are currently unclear. It clearly depends on the relatively impermeable barrier of the stratum corneum (passive regulation) but may also depend on calcium exchanges between keratinocytes and extracellular fluid (active regulation). Using a mathematical model that treats the viable sublayers of unwounded human and murine epidermis as porous media and assumes that their calcium profiles are passively regulated, we demonstrate that these profiles are also actively regulated. To obtain this result, we found that diffusion governs extracellular calcium motion in the viable epidermis and hence intracellular calcium is the main source of the epidermal calcium profile. Then, by comparison with experimental calcium profiles and combination with a hypothesised cell velocity distribution in the viable epidermis, we found that the net influx of calcium ions into keratinocytes from extracellular fluid may be constant and positive throughout the stratum basale and stratum spinosum, and that there is a net outflux of these ions in the stratum granulosum. Hence the calcium exchange between keratinocytes and extracellular fluid differs distinctly between the stratum granulosum and the underlying sublayers, and these differences actively regulate the epidermal calcium profile. Our results also indicate that plasma membrane dysfunction may be an early event during keratinocyte disintegration in the stratum granulosum.

Stop and revive? : the effectiveness of nap and active rest breaks for reducing driver sleepiness

The incidence of sleep-related crashes has been estimated to account for approximately 20% of all fatal and severe crashes. The use of sleepiness countermeasures by drivers is an important component to reduce the incidence rates of sleep-related crashes. Taking a brief nap and stopping for a rest break are two highly publicised countermeasures for driver sleepiness and are also believed by drivers to be the most effective countermeasures. Despite this belief, there is scarce evidence to support the utility of these countermeasures for reducing driver sleepiness levels. Therefore, determining the effectiveness of these countermeasures is an important road safety concern. The current study utilised a young adult sample (N = 20) to investigate the effectiveness of a nap and an active rest break. The countermeasures effects were evaluated by physiological, behavioural (hazard perception skill), and subjective measures previously found sensitive to sleepiness. Participants initially completed two hours of a simulated driving task followed by a 15 minute nap opportunity or a 15 minute active rest break that included 10 minutes of brisk walking. After the break, participants completed one final hour of the simulated driving task. A within-subjects design was used so that each participant completed both the nap and the active rest break conditions on separate occasions. The analyses revealed that only the nap break provided any meaningful reduction in physiological sleepiness, reduced subjective sleepiness levels, and maintained hazard perception performance. In contrast, the active rest break had no effect for reducing physiological sleepiness and resulted in a decrement in hazard perception performance (i.e., an increase of reaction time latencies), with a transient reduction in subjective sleepiness levels. A number of theoretical, empirical and practical issues were identified by the current study.