Predictive genomics: A cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data

We discuss a cancer hallmark network framework for modelling genome-sequencing data to predict cancer clonal evolution and associated clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for a cancer patient, as well as cancer risks for a healthy individual are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized management and prevention of cancer.Comment: 5 figs, related papers, visit lab homepage: http://www.cancer-systemsbiology.org, Seminar in Cancer Biology, 201

How can transport provision and associated built environment infrastructure be enhanced and developed to support the mobility needs of individuals as they age?

First paragraph: Mobility touches every aspect of most of our lives. Restrictions on our mobility are perceived as a loss of freedom, and we seek wherever possible to regain that mobility, or replace it with other forms of mobility. While we immediately think of physical mobility, virtual mobility is increasingly becoming another world that we inhabit and move around in. Older people, however, are the most likely to experience mobility deprivation. The need to be mobile and to travel is related to psychological well-being in older age, and a reduction in mobility can lead to an increase in isolation, loneliness and depression and overall a poorer quality of life. Mobility is important to older people. There are also benefits to society as a whole in increasing travel for older people, including the economic benefits of older people spending more in shops, of them looking after grandchildren, undertaking voluntary work, and carrying out other caring responsibilities. In order to develop a framework of the mobility of people as they age, we formulated a set of guiding principles that underpin this Evidence Review. These principles are drawn from current thinking in applied gerontology in the many differing fields that cover mobility issues and represent a shift from individual discipline-based silo thinking to person-centred thinking that attempts to cross traditional disciplinary boundaries

Comparing personal insight gains due to consideration of a recent dream and consideration of a recent event using the Ullman and Schredl dream group methods

There have been reports and claims in the psychotherapeutic literature that the consideration of recent dreams can result in personal realizations and insight. There is theoretical support for these claims from work on rapid eye movement (REM) sleep having a function of the consolidation of emotional memories and the creative formation of connections between new and older memories. To investigate these claims, 11 participants (10 females, one male) reported and considered a recent home dream in a dream discussion group that following the “Appreciating dreams” method of Montague Ullman. The group ran 11 times, each participant attending and participating once. A further nine participants (seven females, two males) reported and considered a recent home dream in a group that followed the “Listening to the dreamer” method of Michael Schredl. The two studies each had a control condition where the participant also reported a recent event, the consideration of which followed the same technique as was followed for the dream report. Outcomes of the discussions were assessed by the participants on the Gains from Dream Interpretation (GDI) scale, and on its counterpart, the Gains from Event Interpretation scale. High ratings on the GDI experiential-insight subscale were reported for both methods, when applied to dreams, and for the Ullman method Exploration-Insight ratings for the dream condition were significantly higher than for the control event condition. In the Ullman method, self-assessment of personal insight due to consideration of dream content was also significantly higher than for the event consideration condition. The findings support the view that benefits can be obtained from the consideration of dream content, in terms of identifying the waking life sources of dream content, and because personal insight may also occur. To investigate the mechanisms for the findings, the studies should be repeated with REM and non-REM dream reports, hypothesizing greater insight from the former

Insight from the Consideration of REM dreams, Non-REM Dreams and Daydreams

Throughout history there have been reports and claims that consideration of dreams can produce personal realizations and insight. We assessed Exploration-Insight scores associated with discussing Rapid Eye Movement (REM) and non-REM (NREM) dreams in connection with recent waking life experiences. Thirty-one participants were cued in the sleep laboratory for a daydream report and then awakened from REM and N2 sleep for dream reports. Participants subsequently discussed each of their dream and daydream reports for 30-40 minutes with two experimenters, following the structured Ullman (1996) dream group discussion procedure. Participants assessed the benefit of discussing the reports by completing the Gains from (Day)Dream Interpretation (G(D)DI) questionnaire. We found no difference in G(D)DI scores between discussing REM and N2 dream reports, and no difference between dream and daydream discussions in engagement and thoroughness of exploring the reports. However, discussing dream reports produced higher scores on the G(D)DI Exploration-Insight subscale compared with discussing daydream reports. Significant differences were evident in items reflecting the learning of what the report means in terms of waking life issues. Frontal theta prior to waking from N2 was significantly associated with Exploration-Insight score obtained after N2 dream discussion, but this relationship was not found for REM dreams. The findings of high ratings of Exploration-Insight after discussing dreams were evident even though participants did not select the dream, unlike what can occur for home recorded dreams, and even though discussion was brief. We suggest that insight might be produced by embodied and metaphorical thinking in dreams

YourWellness: Designing an Application to Support Positive Emotional Wellbeing in Older Adults

Emotional wellbeing is an important indicator of overall health in adults over 65. For some older people, age-related declines to physical, cognitive or social wellbeing can negatively impact on their emotional wellbeing, as can the notion of growing older, the loss of a spouse, a loss of sense of purpose or general worries about coping, becoming ill and/or death. Yet, within the field of technology design for older adults to support independence, emotional wellbeing is often overlooked. In this paper we describe the design process of an application that supports older adults in monitoring their emotional wellbeing, as well as other parameters of wellbeing they consider important to their overall health. This application also provides informative and useful feedback to support the older person in managing their wellbeing, as well as clinically-based interventions if it is determined that some action or behaviour change is required on the part of the older person. We outline findings from a series of focus groups with older adults that have contributed to the design of the YourWellness application

Network Analysis Reveals A Signaling Regulatory Loop in the PIK3CA-mutated Breast Cancer Predicting Survival Outcome

Mutated genes are rarely common even in the same pathological type between cancer patients and as such, it has been very challenging to interpret genome sequencing data and difficult to predict clinical outcomes. PIK3CA is one of a few genes whose mutations are relatively popular in tumors. For example, more than 46.6% of luminal-A breast cancer samples have PIK3CA mutated, whereas only 35.5% of all breast cancer samples contain PIK3CA mutations. To understand the function of PIK3CA mutations in luminal A breast cancer, we applied our recently-proposed Cancer Hallmark Network Framework to investigate the network motifs in the PIK3CA-mutated luminal A tumors. We found that more than 70% of the PIK3CA-mutated luminal A tumors contain a positive regulatory loop where a master regulator (PDGF-D), a second regulator (FLT1) and an output node (SHC1) work together. Importantly, we found the luminal A breast cancer patients harboring the PIK3CA mutation and this positive regulatory loop in their tumors have significantly longer survival than those harboring PIK3CA mutation only in their tumors. These findings suggest that the underlying molecular mechanism of PIK3CA mutations in luminal A patients can participate in a positive regulatory loop, and furthermore the positive regulatory loop (PDGF-D/FLT1/SHC1) has a predictive power for the survival of the PIK3CA-mutated luminal A patients

Childhood Adversities and Thriving Skills: Sample Case of Older Swiss Former Indentured Child Laborers

OBJECTIVE: The study of life-long consequences of severe childhood adversities or trauma has recently received much attention. However, little is known about the subjective coping success and development of positively evaluated resources that may originate within these adverse experiences and may be conceptualized as thriving. This study set out to examine the relationship between thriving in response to early adversity and successful aging with a sample of former indentured child laborers in Switzerland (Verdingkinder). METHODS: Participants were screened according to subjective and objective health-related attributes, and those who were evaluated to be "successful agers" were included. Semistructured interviews were conducted with 12 former Verdingkinder (mean age: 71 years) that lasted 60-120 minutes. The interviews were analyzed using the paradigm model of the Grounded Theory. RESULTS: In the interviews adverse experiences and negative consequences were reported. However, where thriving was triggered in response to these experiences, the factors identified as "lightheartedness," "social purpose," and "self-enhancement" were associated with successful aging. Factors including motivation, reflection, personality traits, social support, individual coping strategies, turning points, and processing were reported as central to thriving. CONCLUSION: The identified factors show similarities with established predictors of health and well-being. Thus, under certain circumstances early and prolonged adverse experiences can also provide the opportunity to develop positive resources for successful aging

Relating Fractal Dimension to Branching Behaviour in Filamentous Microorganisms

The productivity of an industrial fermentation process involving a filamentous microbe is heavily dependent on the morphological form adopted by the organism. The development of systems capable of rapidly and accurately characterising morphology within a given process represents a significant challenge to biotechnologists, as the complex phenotypes that are manifested are often not easily quantified. Conventional parameters employed in these analyses are of limited value, as they reveal little about the specific branching behaviour of the organism, which is an important consideration given the demonstrated link between branching frequency and metabolite production. More recently, fractal geometry has been employed in the analysis of microbes, but a clear link between fractal dimension and branching behaviour has not been demonstrated. This study presents an alternative means of enumerating the fractal dimension of fungal mycelial structures, by generating a ‘fractal signal’ from an object boundary. In the analysis of a population of Aspergillus oryzae mycelia, both fractal dimension and hyphal growth unit were found to increase together over time. An extensive analysis of different populations of Penicillium chrysogenum and A. oryzae mycelia, cultivated under a variety of different conditions, revealed a strong correlation between fractal dimension and hyphal growth unit. The technique has the potential to be adapted and applied to any morphological form that may be encountered in a fermentation process, providing a universally applicable process parameter for more complete data acquisition

Psychological characteristics and stress differentiate between high from low health trajectories in later life: a machine learning analysis

OBJECTIVE: This study set out to empirically identify joint health trajectories in individuals of advanced age. Predictors of subgroup allocation were investigated to identify the impact of psychological characteristics, stress, and socio-demographic variables on more favorable aging trajectories. METHOD: The sample consisted of N = 334 older adults (M=68.31 years; SD = 9.71). Clustered health trajectories were identified using a longitudinal variant of k-means and were based on health and satisfaction with life. Random forests with conditional interference were computed to examine predictive capabilities. Key predictors included psychological resilience resources, exposure to childhood adversities, and chronic stress. Data was collected via a survey, at two different time points one year apart. RESULTS: Two different clustered health trajectories were identified: A 'constant high health' (low number of health-related symptoms, 65.6%) and a 'maintaining low health' profile (high number of symptoms, 34.4%). Over the one-year study period, both symptom profiles remained stable. Random forest analyses showed chronic stress to be the most important predictor in the interaction with other risk and also buffering factors. CONCLUSION: This study provides empirical evidence for two stable health trajectories in later life over one year. These results highlight the importance of chronic stress, but also psychological resilience resources in predicting aging trajectories