A physical based modeling approach for the dynamic behavior of ultrafine grained structures

This paper discusses some experimental results on the influence of grain refinement on the final mechanical properties of IF and microalloyed steels designed for auto-body components. It shows also some modeling approaches to understanding the dynamic behavior of fine-rained materials. The Zerilli–Armstrong (Z–A) and Khan–Huang–Liang (KHL) models for studied steels were implemented into FEM code in order to simulate the dynamic compression tests with different strain rates.

A mechanistic study on reduced toxicity of irontecan by coadministered thalidomide, a tumor necrosis factor-a inhibitor

Dose-limiting diarrhea and myelosuppression compromise the success of irinotecan (7-ethyl-10-[4-[1-piperidino]-1-piperidino] carbonyloxycamptothecin) (CPT-11)-based chemotherapy. A recent pilot study indicates that thalidomide attenuates the toxicity of CPT-11 in cancer patients. This study aimed to investigate whether coadministered thalidomide modulated the toxicities of CPT-11 and the underlying mechanisms using several in vivo and in vitro models. Diarrhea, intestinal lesions, cytokine expression, and intestinal epithelial apoptosis were
monitored. Coadministered thalidomide (100 mg/kg i.p. for 8 days) significantly attenuated body weight loss, myelosuppression, diarrhea, and intestinal histological lesions caused by CPT-11 (60 mg/kg i.v. for 4 days). This was accompanied by inhibition of tumor necrosis factor-, interleukins 1 and 6 and interferon-, and intestinal epithelial apoptosis. Coadministered
thalidomide also significantly increased the systemic exposure of CPT-11 but decreased that of SN-38 (7-ethyl-10-hydroxycampothecin). It significantly reduced the biliary excretion and cecal exposure of CPT-11, SN-38, and SN-38 glucuronide. Thalidomide hydrolytic products inhibited hydrolysis of CPT-11 in rat liver microsomes but not in primary rat hepatocytes. In addition, thalidomide and its major hydrolytic products, such as phthaloyl glutamic acid (PGA), increased the intracellular accumulation of CPT-11 and SN-38 in primary rat hepatocytes. They also significantly decreased the transport of CPT-11 and SN-38 in Caco-2 and parental MDCKII cells. Thalidomide and PGA also significantly inhibited P-glycoprotein (PgP/MDR1), multidrug resistance-associated protein (MRP1)- and MRP2-mediated CPT-11 and SN-38 transport in MDCKII cells. These results provide insights into the pharmacodynamic and  pharmacokinetic mechanisms for the protective effects of thalidomide against CPT-11-induced intestinal toxicity.

Pharmacokinetic mechanisms for reduced toxicity of irinotecan by coadministered Thalidomide

The clinical use of irinotecan (CPT-11) is hindered by dose-limiting diarrhea and myelosuppression. Recent clinical studies indicate that thalidomide, a known tumor necrosis factor-alpha inhibitor, ameliorated the toxicities induced by CPT-11. However, the mechanisms for this are unknown. This study aimed to investigate whether combination of thalidomide modulated the toxicities of CPT-11 using a rat model and the possible role of the altered pharmacokinetic component in the toxicity modulation using in vitro models. The toxicity model was constructed by treatment of healthy rats with CPT-11 at 60 mg/kg per day by intravenous (i.v.) injection. Body weight, acute and delayed-onset diarrhea, blood cell counts, and macroscopic and microscopic intestinal damages were monitored in rats treated with CPT-11 alone or combined therapy with thalidomide at 100 mg/kg administered by intraperitoneal (i.p.) injection. Single dose and 5-day multiple-dose studies were conducted in rats to examine the effects of concomitant thalidomide on the plasma pharmacokinetics of CPT-11 and its major metabolites SN-38 and SN-38 glucuronide (SN-38G). The effect of CPT-11 on thalidomide's pharmacokinetics was also checked. Rat liver microsomes and a rat hepatoma cell line, H4-II-E cells, were used to study the in vitro metabolic interactions between these two drugs. H4-II-E cells were also used to investigate the effect of thalidomide and its hydrolytic products on the transport of CPT-11 and SN-38. In addition, the effect of thalidomide and its hydrolytic products on rat plasma protein binding of CPT-11 and SN-38 was examined. Administration of CPT-11 by i.v. for 4 consecutive days to rats induced significant body weight loss, decrease in neutrophil and lymphocyte counts, severe acute- and delayed-onset diarrhea, and intestinal damages. These toxicities were alleviated when CPT-11 was combined with thalidomide. In both single-dose and 5-day multiple-dose pharmacokinetic study, coadministered thalidomide significantly increased the area under the plasma concentration-time curve (AUC) of CPT-11, but the AUC and elimination half-life (t(1/2)) of SN-38 were significantly decreased. However, CPT-11 did not significantly alter the pharmacokinetics of thalidomide. Thalidomide at 25 and 250 microM and its hydrolytic products at a total concentration of 10 microM had no significant effect on the plasma protein binding of CPT-11 and SN-38, except for that thalidomide at 250 microM caused a significant increase in the unbound fraction (f(u)) of CPT-11 by 6.7% (P < 0.05). The hydrolytic products of thalidomide (total concentration of 10 microM), but not thalidomide, significantly decreased CPT-11 hydrolysis by 16% in rat liver microsomes (P < 0.01). The formation of both SN-38 and SN-38G from CPT-11, SN-38 glucuronidation, or intracellular accumulation of both CPT-11 and SN-38 in H4-II-E cells followed Michaelis-Menten kinetics with the one-binding site model being the best fit for the kinetic data. Coincubation or 2-hr preincubation of thalidomide at 25 microM and 250 microM and its hydrolytic products at 10 microM did not show any significant effects on CPT-11 hydrolysis and SN-38 glucuronidation. However, preincubation of H4-II-E cells with thalidomide (250 microM), its hydrolytic products (total concentration of 10 microM), or phthaloyl glutamic acid (one major thalidomide hydrolytic product, 10 microM) significantly increased the intracellular accumulation of SN-38, but not CPT-11 (P < 0.01). The dose-limiting toxicities of CPT-11 were alleviated by combination with thalidomide in rats and the pharmacokinetic modulation by thalidomide may partially explain its antagonizing effects on the toxicities of CPT-11. The hydrolytic products of thalidomide, instead of the parental drug, modulated the hepatic hydrolysis of CPT-11 and intracellular accumulation of SN-38, probably contributing to the altered plasma pharmacokinetics of CPT-11 and SN-38. Further studies are needed to explore the role of both pharmacokinetics and pharmacodynamic components in the protective effect of thalidomide against the toxicities of CPT-11.

Environmental factors associated with adults' participation in physical activity- a review

Background: Promoting physical activity is a public health priority, and changes in the environmental contexts of adults’ activity choices are believed to be crucial. However, of the factors associated with physical activity, environmental influences are among the least understood. Method: Using journal scans and computerized literature database searches, we identified 19 quantitative studies that assessed the relationships with physical activity behavior of perceived and objectively determined physical environment attributes. Findings were categorized into those examining five categories: accessibility of facilities, opportunities for activity, weather, safety, and aesthetic attributes. Results: Accessibility, opportunities, and aesthetic attributes had significant associations with physical activity. Weather and safety showed less-strong relationships. Where studies pooled different categories to create composite variables, the associations were less likely to be statistically significant. Conclusions: Physical environment factors have consistent associations with physical activity behavior. Further development of ecologic and environmental models, together with behavior-specific and context-specific measurement strategies, should help in further  understanding of these associations. Prospective studies are required to identify possible causal relationships.

Decision-making models used by `graduate nurses` managing patients` medications

Background. Nurses in a graduate programme in Australia are those who are in the first year of clinical practice following completion of a 3-year undergraduate nursing degree. When working in an acute care setting, they need to make complex and ever-changing decisions about patients' medications in a clinical environment affected by multifaceted, contextual issues. It is important that comprehensive information about graduate nurses' decision-making processes and the contextual influences affecting these processes are obtained in order to prepare them to meet patients' needs.
Aim. The purpose of this paper is to report a study that sought to answer the following questions: What are the barriers that impede graduate nurses' clinical judgement in their medication management activities? How do contextual issues impact on graduate nurses' medication management activities? The decision-making models considered were: hypothetico-deductive reasoning, pattern recognition and intuition.
Methods. Twelve graduate nurses who were involved in direct patient care in medical and surgical wards of a metropolitan teaching hospital located in Melbourne, Australia participated in the study. Participant observations were conducted with the graduate nurses during a 2-hour period during the times when medications were being administered to patients. Graduate nurses were also interviewed to elicit further information about how they made decisions about patients' medications.
Results. The most common model used was hypothetico-deductive reasoning, followed by pattern recognition and then intuition. The study showed that graduate nurses had a good understanding of how physical assessment affected whether medications should be administered or not. When negotiating treatment options, graduate nurses readily consulted with more experienced nursing colleagues and doctors.
Study limitations. It is possible that graduate nurses demonstrated a raised awareness of managing patients' medications as a consequence of being observed.
Conclusions. The complexity of the clinical practice setting means that graduate nurses need to adapt rapidly to make sound and appropriate decisions about patient care.

Understanding and influencing physical activity to improve health outcomes

Participation in physical activity is associated with significant benefits to health. We provide an overview of research relevant to understanding and influencing health-enhancing physical activity in adults. We describe a behavioural epidemiology framework that is designed to integrate the range of studies in the field; give brief examples of studies on the relationships between physical activity and health outcomes; and, we consider descriptive studies of adult populations on levels of participation. We describe research findings on the correlates of physical activity participation; describe ecological models of health behaviour that may be used in understanding and influencing physical activity; and, we review research findings on how environmental attributes can influence adults’ physical activity, particularly walking. There is considerable potential to use evidence-based approaches to increase the physical activity levels of whole populations, particularly through a focus on developing the attributes of community environments that can promote walking.

Year 12 students' mental models of the nature of light

This paper reports on the third year of a three-year longitudinal investigation into six Year 10 secondary students’ understanding of optics at a secondary school level. During the first two years of the study the students’ understanding of geometrical optics was explored with the adoption of constructivist teaching and learning strategies. The students' understanding of geometrical optics following the Year 11 teaching stage then formed the basis of exploration of their mental models of the nature of light. This exploration occurred before, during and following a Year 12 teaching stage where the students studied physical optics and quantum ideas. Before the Year 12 teaching stage the students had constructed mental models of light that related to their understanding of a ray. Over the Year 12 teaching stage the students’ mental models changed to conceptualizations of a photon. There was evidence in the students’ mental models of a hybridization of the particle and wave scientific models. That is, they conceptualized the photon as having both wave and particle characteristics. The variation in the students’ hybrid models also suggested a variation in the way they conceived of the nature of scientific models.

Associations of neighbourhood greenness with physical and mental health : do walking, social coherence and local social interaction explain the relationships?

Background: Studies have shown associations between health indices and access to “green” environments but the underlying mechanisms of this association are not clear.

Objectives: To examine associations of perceived neighbourhood “greenness” with perceived physical and mental health and to investigate whether walking and social factors account for the relationships.

Methods: A mailed survey collected the following data from adults (n  =  1895) in Adelaide, Australia: physical and mental health scores (12-item short-form health survey); perceived neighbourhood greenness; walking for recreation and for transport; social coherence; local social interaction and sociodemographic variables.

Results: After adjusting for sociodemographic variables, those who perceived their neighbourhood as highly green had 1.37 and 1.60 times higher odds of better physical and mental health, respectively, compared with those who perceived the lowest greenness. Perceived greenness was also correlated with recreational walking and social factors. When walking for recreation and social factors were added to the regression models, recreational walking was a significant predictor of physical health; however, the association between greenness and physical health became non-significant. Recreational walking and social coherence were associated with mental health and the relationship between greenness and mental health remained significant.

Conclusions: Perceived neighbourhood greenness was more strongly associated with mental health than it was with physical health. Recreational walking seemed to explain the link between greenness and physical health, whereas the relationship between greenness and mental health was only partly accounted for by recreational walking and social coherence. The restorative effects of natural environments may be involved in the residual association of this latter relationship.

How socio-economic status contributes to participation in leisure-time physical activity

The aim of this cross-sectional study was to identify individual, social, and environmental contributors (mediators) to individual- and area-level differences in leisure-time physical activity across socio-economic groups. A two-stage stratified sampling design was used to recruit 20–65 year old adults (N = 2194) living in 154 census collection districts of Adelaide, Australia (overall response rate: 12%). Participants completed two surveys six months apart (response rate on the second survey: 83%). Individual-level socio-economic status (SES) was assessed using self-report measures on educational attainment, household income, and household size. Area-level SES was assessed using census data on median household income and household size for each selected census district. Bootstrap generalized linear models were used to examine associations between SES, potential mediators, and leisure-time physical activity. The product-of-coefficient test was used to estimate mediating effects. All SES measures were independently associated with potential individual and social mediators of the SES-activity relationships. Individual- and area-level income was also associated with perceived neighborhood attributes. Self-efficacy and social support for physical activity explained virtually all of the differences in physical activity across educational attainment groups. Physical barriers to walking and access to public open space contributed in part to the explanation of differences in recreational walking across income groups. Yet, self-efficacy and social support were the key mediators of the observed relationships between individual- and area-level income and physical activity. This study suggests that in order to increase physical activity participation in the more disadvantaged segments of the population, comprehensive, multilevel interventions targeting activity-related attitudes and skills as well as social and physical environments are needed.

Sociocultural factors relating to Tongans' and Indigenous Fijians' patterns of eating, physical activity and body size

This paper reviews literature between 1974 and 2007 that addresses the impact of sociocultural factors on reported patterns of eating, physical activity (activity) and body size of Tongans and indigenous Fijians (Fijians) in their countries of origin. There have been changes in diet (more imported and fewer traditional foods), activity (reduced, especially in urban settings), residence (rural-urban shift) and body size (increased obesity and at a younger age). The prevalence of overweight/obesity in Tongans and Fijians has increased rapidly over the last two decades and remains among the highest in the world (>80% in Tonga; >40% in Fiji), with more females reported to be obese than males. The few studies that investigated sociocultural influences on patterns of eating, activity and/or body size in this population have examined the impact of hierarchical organisation, rank and status (sex, seniority), values (respect, care, co-operation) and/or role expectations. It is important to examine how sociocultural factors influence eating, activity and body size in order to i) establish factors that promote or protect against obesity, ii) inform culturally-appropriate interventions to promote healthy lifestyles and body size, and iii) halt the obesity epidemic, especially in cultural groups with a high prevalence of obesity. There is an urgent need for more systematic investigations of key sociocultural factors, whilst taking into account the complex interplay between sociocultural factors, behaviours and other influences (historical; socioeconomic; policy; external global influences; physical environment).

Perceived sports competence mediates the relationship between childhood motor skill proficiency and adolescent physical activity and fitness : a longitudinal assessment

Background: The purpose of this paper was to investigate whether perceived sports competence mediates the relationship between childhood motor skill proficiency and subsequent adolescent physical activity and fitness.

Methods: In 2000, children's motor skill proficiency was assessed as part of a school-based physical activity intervention. In 2006/07, participants were followed up as part of the Physical Activity and Skills Study and completed assessments for perceived sports competence (Physical Self-Perception Profile), physical activity (Adolescent Physical Activity Recall Questionnaire) and cardiorespiratory fitness (Multistage Fitness Test). Structural equation modelling techniques were used to determine whether perceived sports competence mediated between childhood object control skill proficiency (composite score of kick, catch and overhand throw), and subsequent adolescent self-reported time in moderate-to-vigorous physical activity and cardiorespiratory fitness.

Results: Of 928 original intervention participants, 481 were located in 28 schools and 276 (57%) were assessed with at least one follow-up measure. Slightly more than half were female (52.4%) with a mean age of 16.4 years (range 14.2 to 18.3 yrs). Relevant assessments were completed by 250 (90.6%) students for the Physical Activity Model and 227 (82.3%) for the Fitness Model. Both hypothesised mediation models had a good fit to the observed data, with the Physical Activity Model accounting for 18% (R2 = 0.18) of physical activity variance and the Fitness Model accounting for 30% (R2 = 0.30) of fitness variance. Sex did not act as a moderator in either model.

Conclusion: Developing a high perceived sports competence through object control skill development in childhood is important for both boys and girls in determining adolescent physical activity participation and fitness. Our findings highlight the need for interventions to target and improve the perceived sports competence of youth.

Physical activity and likelihood of depression in adults : a review

Objective : This review examines original research which has investigated associations between physical activity (PA) dose (i.e. frequency, intensity and duration) and domain and depression or symptoms of depression in adults.

Methods : A search of electronic databases and authors' own bibliographic libraries was performed between 2006 and 2007 for original research articles investigating associations between PA and depression in adults. A total of 27 observational and 40 intervention studies were included.

Results : Of the studies that focused on the association between duration of PA and likelihood of depression, all five observational studies, and five of the seven intervention studies found both shorter and longer durations of PA were associated with reduced likelihood of depression. Of the studies that focused on the association between intensity of PA and likelihood of depression, four of the six observational studies found that vigorous-intensity PA was more strongly associated with decreased likelihood of depression than lower intensities. Most intervention studies showed that both intensities were effective in reducing the likelihood of depression. Two observational studies found a stronger inverse relationship of leisure-time PA with depression than PA in other domains. There is insufficient evidence regarding the importance of the PA setting on depression.

Conclusion : Although the dose and domain of physical activity varied across studies reviewed, evidence suggests that even low doses of PA may be protective against depression. Further studies examining the optimal domain of PA for reducing the likelihood of depression are needed.

The association between physical activity and depressive symptoms in young women : a review

Objective : This review synthesises results of studies examining the association between physical activity (PA) and depressive symptoms and the effects of PA intervention studies on depression among young women.
Methods : A search of electronic databases and bibliographic searches of observational and intervention studies was conducted that included women between the ages of 18 and 35.
Results : A total of eight observational and five intervention studies were identified. Evidence from observational studies indicated that physical activity was inversely associated with depressive symptoms in young women. Even a small amount of physical activity was found to be associated with reduced depressive symptoms. No clear dose–response relationship was shown. Evidence from intervention studies indicated that physical activity reduced depressive symptoms. Direct study comparisons were difficult due to variations in study methods and measures. The studies provided little or no information on understanding dose–response effects or on the mechanisms involved.
Conclusion : The limited number of studies examining physical activity and depressive symptoms in young women and the methodological problems identified in a number of these studies, make it difficult to draw firm conclusions. However, this review suggests that engaging in even low levels of physical activity may be protective against depressive symptoms in young women. There is a need for objective measures of physical activity in future studies, particularly with a focus on those with clinical depression in non-student populations.

A comparison of subjective and objective measures of physical activity and fitness in identifying associations with cardiometabolic risk factors

Purpose
To compare the ability of alternative measures of physical activity and fitness to quantify associations with health outcomes.

Methods
Associations between a range of subjective and objective physical activity and fitness measures and cardiometabolic risk factors were examined using data from 1,631 Australians aged 26–36 years. Anthropometry, fitness, blood pressure, and fasting blood glucose, insulin, and lipids were measured at study clinics. Participants completed the International Physical Activity Questionnaire (IPAQ) and 7-day pedometer diaries; they also reported sedentary behavior (sitting, television viewing).

Results
In men and women, associations were strongest for fitness, with those in the highest (vs. lowest) fitness quarter having a 75% to 80% lower prevalence of two or more primary risk factors (waist circumference, high-density lipoprotein cholesterol, and insulin resistance). In men, a 60% to 70% reduced prevalence of two or more risk factors was observed across extreme quarters of IPAQ leisure, IPAQ vigorous, sitting duration, and pedometer measures. Similar reductions in prevalence were observed only across extreme quarters of pedometer activity and television viewing in women.

Conclusions
Associations between alternative measures and cardiometabolic risk were relatively independent, suggesting that a range of physical activity and fitness measures may be needed to most accurately quantify associations between physical activity and health.

Developing recreation programs for disadvantaged sectors of the community

Physical activity participation can provide benefits for both the health and well-being of the community. Many people, however, are not active enough to achieve these health and well-being outcomes. The Victorian Health Promotion Foundation’s (VicHealth) 2001 Active Recreation Scheme funded 27 projects designed to provide recreation programs to address the active recreation needs of disadvantaged groups who are often the least physically active members of Victorian communities. This research aimed to identify themes and strategies of these projects that increased participation or reduced barriers to participation in active recreation. Site visit interviews were conducted with representatives of 11 projects to become familiar with successful program strategies and barriers to recreation program development. Following the site visits a focus group discussion with representatives from all 27 funded projects was conducted to explore ways in which barriers to recreation participation could be minimized and what strategies were effective in increasing recreation participation. Nine general dimensions that were identified as strategic approaches to increase the participation of disadvantaged groups in recreation programs were relationships, resources, community values/attitudes, communication (promotion and education), participant awareness/motivation, autonomy supportive, planning, program design, and mentors/role models. It was found that a focus on a community coalitions and complementary policy developments had positive effects on creating active communities. Four themes that guided the community and policy developments were i) community partnerships, ii) community support, iii) focus on the participants and iv) program design elements. The study also showed that the management and manipulation of these themes assisted agencies to develop programs that increased recreation participation.