Does activity in computer game play have an impact on creative behavior?

This paper describes a behaviour analysis designed to measure the creative potential of computer game activities. The research approach applies a behavioural and verbal protocol to analyze the factors that influence the creative processes used by people as they play computer games from the puzzle genre. Creative components are measured by examining task motivation as well as domain-relevant and creativity-relevant skills factors. This paper focuses on how three puzzle games embody activity that might facilitate creative processes. The findings show that game playing activities significantly impact upon creative potential of computer games.

Exploring the role of activity in genre

This paper provides an outline of genre as we currently know it, and examines the changes occurring as games become more complex. Recent research we've undertaken suggests that our perception of which games fall into which genre category is subjective and that genre hybridization continues to blur our understanding of these categories. Consequently, it is becoming increasingly difficult to categorise game play experience based on traditional genre classifications. We examine the use of videogame activities as a useful mechanism for supplementing our understanding of videogame genre. Through considering activity as a means of classifying game experiences we may obtain a much more nuanced understanding of how players engage with games within a particular genre and across genres.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

A phase II study of Caelyx, liposomal doxorubicin : lack of activity in patients with advanced gastric cancer

Purpose A phase II study was designed to assess the efficacy and safety of Caelyx (liposomal doxorubicin) in patients with advanced or metastatic gastric cancer. Methods A total of 25 patients with gastric adenocarcinoma were treated with Caelyx 45 mg/m2 every 28 days as first-line therapy for advanced disease. Patients were treated until tumour progression or unacceptable toxicity. Results One patient was withdrawn from the study after experiencing a severe infusion reaction. Of the 24 evaluable patients, 1 had a partial response, 7 had stable disease and the others progressed. Side effects, in particular palmar-plantar erythrodysaesthesia and haematological toxicity, were minor. Conclusions We conclude that while this dose and schedule of Caelyx in this patient group is acceptable, further studies with this regimen cannot be recommended due to the lack of antitumour activity seen.

Correlating flow induced shear stress and chondrocytes activity in micro-porous scaffold using computational fluid dynamics and rapid prototyping

Flow induced shear stress plays an important role in regulating cell growth and distribution in scaffolds. This study sought to correlate wall shear stress and chondrocytes activity for engineering design of micro-porous osteochondral grafts based on the hypothesis that it is possible to capture and discriminate between the transmitted force and cell response at the inner irregularities. Unlike common tissue engineering therapies with perfusion bioreactors in which flow-mediated stress is the controlling parameter, this work assigned the associated stress as a function of porosity to influence in vitro proliferation of chondrocytes. D-optimality criterion was used to accommodate three pore characteristics for appraisal in a mixed level fractional design of experiment (DOE); namely, pore size (4 levels), distribution pattern (2 levels) and density (3 levels). Micro-porous scaffolds (n=12) were fabricated according to the DOE using rapid prototyping of an acrylic-based bio-photopolymer. Computational fluid dynamics (CFD) models were created correspondingly and used on an idealized boundary condition with a Newtonian fluid domain to simulate the dynamic microenvironment inside the pores. In vitro condition was reproduced for the 3D printed constructs seeded by high pellet densities of human chondrocytes and cultured for 72 hours. The results showed that cell proliferation was significantly different in the constructs (p<0.05). Inlet fluid velocity of 3×10-2mms-1 and average shear stress of 5.65×10-2 Pa corresponded with increased cell proliferation for scaffolds with smaller pores in hexagonal pattern and lower densities. Although the analytical solution of a Poiseuille flow inside the pores was found insufficient for the description of the flow profile probably due to the outside flow induced turbulence, it showed that the shear stress would increase with cell growth and decrease with pore size. This correlation demonstrated the basis for determining the relation between the induced stress and chondrocyte activity to optimize microfabrication of engineered cartilaginous constructs.

Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.

Light exposure and physical activity in myopic and emmetropic children

Purpose: To objectively assess daily light exposure and physical activity levels in myopic and emmetropic children. Methods: One hundred and two children (41 myopes and 61 emmetropes) aged 10 to 15 years old had simultaneous objective measures of ambient light exposure and physical activity collected over a 2 week period during school term, using a wrist worn actigraphy device (Actiwatch-2). Measures of visible light illuminance and physical activity were captured every 30 seconds, 24 hours a day over this period. Mean hourly light exposure and physical activity for weekdays and weekends were examined. To ensure that seasonal variations didn’t confound comparisons, the light and activity data of the 41 myopes, was compared with 41 age and gender matched emmetropes who wore the Actiwatch over the same two week period. Results: Mean light exposure and physical activity for all 101 children with valid data exhibited significant changes with time of day and day of the week (p<0.0001). On average greater daily light exposure occurred on weekends compared to weekdays (p<0.05), and greater physical activity occurred on weekdays compared to weekends (p<0.01). Myopic children (n = 41, mean daily light exposure 915 ± 519 lux) exhibited significantly lower average light exposure compared to 41 age and gender matched emmetropic children (1272 ± 625 lux, p<0.01). The amount of daily time spent in bright light conditions (>1000 lux) was also significantly greater in emmetropes (127 ± 51 minutes) compared to myopes (91 ± 44 minutes, p<0.001). No significant differences were found between the average daily physical activity levels of myopes and emmetropes (p>0.05). Conclusions: Myopic children exhibit significantly lower daily light exposure, but no significant difference in physical activity compared to emmetropic children. This suggests the important factor involved in documented associations between myopia and outdoor activity is likely exposure to bright outdoor light rather than greater physical activity.

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

Evidence of effectiveness : high level synthesis of research to prevent obesity and increase physical activity in children

Background Prevention of childhood obesity is a public health priority for Malaysia and many other countries. Physical activity for children is also decreasing at an alarming rate. Both conditions are associated with non-communicable diseases and with significant morbidity and mortality in later life. Systematic reviews of public health interventions provide a useful summary to inform public health practice by combining the results of a range of research studies on a specific intervention into a single report. Systematic reviews are deemed most valuable for health program development and evidence based practice. Unfortunately, many policy makers and practitioners are simply unaware of the evidence: which strategies which are most likely to provide benefit; and which strategies are known to be harmful or useless. This presentation provides a “birds eye” overview based upon recent (since 2007 to present) high quality systematic reviews of public health interventions. Method HealthEvidece.org and the Cochrane Library were searched for systematic reviews which evaluated interventions targeting obesity prevention and increasing physical activity for children. The findings of the included reviews were themed and summarized. Results Seven reviews were identified addressing obesity in the early years, and fifteen reviews addressing obesity more broadly in childhood. Additional reviews were identified aimed at increasing physical activity. The synthesis shows several strategies to be effective, however many popular strategies clearly are not. Several of the reviews were inconclusive due to an absence of robust primary studies. Amongst the findings, interventions undertaken in the school setting appear very promising. Conclusions There is significant evidence from systematic reviews to guide public health practice and policy, and to inform future research.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. Because fMRI records, through the monitoring of blood flow activity, the location of localised brain activity within the brain, the possibility of combining fMRI measurements with EEG, as a joint inversion activity, was discussed and examined in detail. (3) A major goal for the BRI is to improve understanding about ``when'' (at what time) an epileptic seizure actually commenced before it is identified on an eeg recording, ``where'' the source of this initiation is located in the brain, and ``what'' is the initiator. Because of the general agreement in the literature that, in one way or another, epileptic events and seizures represent abnormal synchronisations of localised and/or global brain activity the modelling of synchronisations was examined in some detail. References C. M. Michel, G. Thut, S. Morand, A. Khateb, A. J. Pegna, R. Grave de Peralta, S. Gonzalez, M. Seeck and T. Landis, Electric source imaging of human brain functions, Brain Res. 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Age and gender differences in objectively measured physical activity in youth

Purpose The purpose of this study was to evaluate age and gender differences in objectively measured physical activity (PA) in a population-based sample of students in grades 1–12. Methods Participants (185 male, 190 female) wore a CSA 7164 accelerometer for 7 consecutive days. To examine age-related trends, students were grouped as follows: grades 1–3 (N = 90), grades 4–6 (N = 91), grades 7–9 (N = 96), and grades 10–12 (N = 92). Bouts of PA and minutes spent in moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) were examined. Results Daily MVPA and VPA exhibited a significant inverse relationship with grade level, with the largest differences occurring between grades 1–3 and 4–6. Boys were more active than girls; however, for overall PA, the magnitudes of the gender differences were modest. Participation in continuous 20-min bouts of PA was low to nonexistent. Conclusion Our results support the notion that PA declines rapidly during childhood and adolescence and that accelerometers are feasible alternatives to self-report methods in moderately sized population-level surveillance studies.

Physical activity and determinants of physical activity in obese and non-obese children

OBJECTIVE To compare the physical activity (PA) patterns and the hypothesized psychosocial and environmental determinants of PA in an ethnically diverse sample of obese and non-obese middle school children. DESIGN Cross-sectional study. SUBJECTS One-hundred and thirty-three non-obese and 54 obese sixth grade children (mean age of 11.4 +/-0.6). Obesity status determined using the age-, race- and gender-specific 95th percentile for BMI from NHANES-1. MEASUREMENTS Objective measurements were collected of PA over a 7-day period using the CSA 7164 accelerometer: total daily counts; daily moderate (3-5.9 METs) physical activity (MPA); daily vigorous physical activity (greater than or equal to 6 METs; VPA); and weekly number of 5, 10 and 20 min bouts of moderate-to-vigorous physical activity (greater than or equal to 3 METs, MVPA). Self-report measures were collected of PA self-efficacy; social influences regarding PA, beliefs about PA outcomes; perceived PA levels of parents and peers, access to sporting and/or fitness equipment at home, involvement in community-based PA organizations; participation in community sports teams; and hours spent watching television or playing video games. RESULTS Compared to their non-obese counterparts, obese children exhibited significantly lower daily accumulations of total counts, MPA and VPA as well as significantly fewer 5, 10 and 20 min bouts of MVPA. Obese children reported significantly lower levels of PA self-efficacy, were involved in significantly fewer community organizations promoting PA and were significantly less likely to report their father or male guardian as physically active. CONCLUSIONS The results are consistent with the hypothesis that physical inactivity is an important contributing factor in the maintenance of childhood obesity. Interventions to promote PA in obese children should endeavor to boost self-efficacy perceptions regarding exercise, increase awareness of, and access to, community PA outlets, and increase parental modeling of PA.

Assessing physical activity during youth sport : the observational system for recording activity in children : youth sports (OSRAC:YS)

The purpose of this study was to evaluate the validity and inter-rater reliability of the Observation System for Recording Activity in Children: Youth Sports (OSRAC:YS). Children (N=29) participating in a parks and recreation soccer program were observed during regularly scheduled practices. Physical activity (PA) intensity and contextual factors were recorded by momentary time-sampling procedures (10-sec observe, 20-sec record). Two observers simultaneously observed and recorded children's PA intensity, practice context, social context, coach behavior, and coach proximity. Inter-rater reliability was based on agreement (Kappa) between the observer's coding for each category, and the Intraclass Correlation Coefficient (ICC) for percent of time spent in MVPA. Validity was assessed by calculating the correlation between OSRAC:YS estimated and objectively measured MVPA. Kappa statistics for each category demonstrated substantial to almost perfect inter-observer agreement (Κappa = 0.67 to 0.93). The ICC for percent time in MVPA was 0.76 (95% C.I. = 0.49 - 0.90). A significant correlation (r = 0.73) was observed for MVPA recorded by observation and MVPA measured via accelerometry. The results indicate the OSRAC:YS is a reliable and valid tool for measuring children's PA and contextual factors during a youth soccer practice.

Alterations in cervical muscle activity in functional and stressful tasks in female office workers with neck pain

This study determined differences between computer workers with varying levels of neck pain in terms of work stressors, employee strain, electromyography (EMG) amplitude and heart rate response to various tasks. Participants included 85 workers (33, no pain; 38, mild pain; 14, moderate pain) and 22 non-working controls. Work stressors evaluated were job demands, decision authority, and social support. Heart rate was recorded during three tasks: copy-typing, typing with superimposed stress and a colour word task. Measures included electromyography signals from the sternocleidomastoid (SCM), anterior scalene (AS), cervical extensor (CE) and upper trapezius (UT) muscles bilaterally. Results showed no difference between groups in work stressors or employee strain measures. Workers with and without pain had higher measured levels of EMG amplitude in SCM, AS and CE muscles during the tasks than controls (all P < 0.02). In workers with neck pain, the UT had difficulty in switching off on completion of tasks compared with controls and workers without pain. There was an increase in heart rate, perceived tension and pain and decrease in accuracy for all groups during the stressful tasks with symptomatic workers producing more typing errors than controls and workers without pain. These findings suggest an altered muscle recruitment pattern in the neck flexor and extensor muscles. Whether this is a consequence or source of the musculoskeletal disorder cannot be determined from this study. It is possible that workers currently without symptoms may be at risk of developing a musculoskeletal disorder.