Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women

Lean body mass (LBM) and muscle mass remains difficult to quantify in large epidemiological studies due to non-availability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n= 2220; 36% females; age 18-79 y) representing a wide range of body mass index (14-44 kg/m2) participated in this study. Their LBM including ALST was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height and weight explained > 90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of SFTs) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all the above anthropometric variables could predict the DXA measured LBM and ALST accurately as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively) as well as good agreement by Bland Altman analyses. These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.

Investigating the association between sun exposure and folate degradation in the human body

This thesis is the first study to investigate the associations between sun exposure and folate degradation in a group of childbearing age women in a high UV environment. It examined whether the degree of sun exposure experienced by women influenced blood folate levels following a period of folic acid supplementation and found a strong significant relationship between increased sun exposure and folate degradation. This relationship has strong implications for public health and the thesis has provided a foundation for further research in this area.

Associations of body mass index and waist circumference with: energy intake and percentage energy from macronutrients, in a cohort of Australian children

Background It is evident from previous research that the role of dietary composition in relation to the development of childhood obesity remains inconclusive. Several studies investigating the relationship between body mass index (BMI), waist circumference (WC) and/or skin fold measurements with energy intake have suggested that the macronutrient composition of the diet (protein, carbohydrate, fat) may play an important contributing role to obesity in childhood as it does in adults. This study investigated the possible relationship between BMI and WC with energy intake and percentage energy intake from macronutrients in Australian children and adolescents. Methods Height, weight and WC measurements, along with 24 h food and drink records (FDR) intake data were collected from 2460 boys and girls aged 5-17 years living in the state of Queensland, Australia. Results Statistically significant, yet weak correlations between BMI z-score and WC with total energy intake were observed in grades 1, 5 and 10, with only 55% of subjects having a physiologically plausible 24 hr FDR. Using Pearson correlations to examine the relationship between BMI and WC with energy intake and percentage macronutrient intake, no significant correlations were observed between BMI z-score or WC and percentage energy intake from protein, carbohydrate or fat. One way ANOVAs showed that although those with a higher BMI z-score or WC consumed significantly more energy than their lean counterparts. Conclusion No evidence of an association between percentage macronutrient intake and BMI or WC was found. Evidently, more robust longitudinal studies are needed to elucidate the relationship linking obesity and dietary intake.

Tissue viability imaging of skin microcirculation following exposure to whole body cryotherapy (-110°C) and cold water immersion (8°C)

Cryotherapy is currently used in various clinical, rehabilitative, and sporting settings. However, very little is known regarding the impact of cooling on the microcirculatory response. Objectives: The present study sought to examine the influence of two commonly employed modalities of cryotherapy, whole body cryotherapy (WBC; -110°C) and cold water immersion(CWI; 8±1°C), on skin microcirculation in the mid- thigh region. Methods: The skin area examined was a 3 × 3 cm located between the most anterior aspect of the inguinal fold and the patella. Following 10 minutes of rest, 5 healthy, active males were exposed to either WBC for 3 minutes or CWI for 5 minutes in a randomised order. Volunteers lay supine for five minutes after treatment, in order to monitor the variation of red blood cell (RBC) concentration in the region of interest for a duration of 40 minutes. Microcirculation response was assessed using a non-invasive, portable instrument known as a Tissue Viability imaging system. After a minimum of seven days, the protocol was repeated. Subjective assessment of the volunteer’s thermal comfort and thermal sensation was also recorded. Results: RBC was altered following exposure to both WBC and CWI but appeared to stabilise approximately 35 minutes after treatments. Both WBC and CWI affected thermal sensation (p < 0.05); however no betweengroup differences in thermal comfort or sensation were recorded (p > 0.05). Conclusions: As both WBC and CWI altered RBC, further study is necessary to examine the mechanism for this alteration during whole body cooling.

No sex difference in body fat in response to supervised and measured exercise

It is often reported that females lose less body weight than males do in response to exercise. These differences are suggested to be a result of females exhibiting a stronger defense of body fat and a greater compensatory appetite response to exercise than males do. Purpose This study aimed to compare the effect of a 12-wk supervised exercise program on body weight, body composition, appetite, and energy intake in males and females. Methods A total of 107 overweight and obese adults (males = 35, premenopausal females = 72, BMI = 31.4 ± 4.2 kg·m−2, age = 40.9 ± 9.2 yr) completed a supervised 12-wk exercise program expending approximately 10.5 MJ·wk−1 at 70% HRmax. Body composition, energy intake, appetite ratings, RMR, and cardiovascular fitness were measured at weeks 0 and 12. Results The 12-wk exercise program led to significant reductions in body mass (males [M] = −3.03 ± 3.4 kg and females [F] = −2.28 ± 3.1 kg), fat mass (M = −3.14 ± 3.7 kg and F = −3.01 ± 3.0 kg), and percent body fat (M = −2.45% ± 3.3% and F = −2.45% ± 2.2%; all P < 0.0001), but there were no sex-based differences (P > 0.05). There were no significant changes in daily energy intake in males or females after the exercise intervention compared with baseline (M = 199.2 ± 2418.1 kJ and F = −131.6 ± 1912.0 kJ, P > 0.05). Fasting hunger levels significantly increased after the intervention compared with baseline values (M = 11.0 ± 21.1 min and F = 14.0 ± 22.9 mm, P < 0.0001), but there were no differences between males and females (P > 0.05). The exercise also improved satiety responses to an individualized fixed-energy breakfast (P < 0.0001). This was comparable in males and females. Conclusions Males and premenopausal females did not differ in their response to a 12-wk exercise intervention and achieved similar reductions in body fat. When exercise interventions are supervised and energy expenditure is controlled, there are no sex-based differences in the measured compensatory response to exercise.

Exploring schema-driven differences in situation awareness between road users : an on-road study of driver, cyclist and motorcyclist situation awareness

Collisions between different road users make a substantial contribution to road trauma. Although evidence suggests that different road users interpret the same road situations differently, it is not clear how road users' situation awareness differs, nor is it clear which differences might lead to conflicts. This article presents the findings from an on-road study conducted to examine driver, motorcyclist and cyclist situation awareness in different road environments. The findings suggest that, in addition to minor differences in the structure of different road users' situation awareness (i.e. amount of information and how it is integrated), the actual content of situation awareness in terms of road user schemata, the resulting interaction with the world and the information underpinning situation awareness is markedly different. Further examination indicates that the differences are likely to be compatible along arterial roads, shopping strips and at roundabouts, but that they may create conflicts between different road users at intersections. Interventions designed to support compatible situation awareness and behaviour between different road users are discussed. Practitioner Summary: Incompatible situation awareness plays a key role in collisions between different road users (e.g. drivers and motorcyclists). This on-road study examined situation awareness in drivers, motorcyclists and cyclists, identifying the key differences and potential conflicts that arise. The findings are used to propose interventions designed to enhance the compatibility of situation awareness between road users.

Body stories

This research is in the field of arts education. Eisner claims that ‘teachers rarely view themselves as artists’ (Taylor, 1993:21). Situating professional dance artists and teacher-artists (Mc Lean, 2009) in close proximity to classroom dance teachers, spatially, through a shared rehearsal studio and creatively, by engaging them in a co-artistry approach, allows participants to map unique and new creative processes, kinaesthetically and experientially. This pratice encourages teachers to attune and align themselves with artists’ states of mind and enables them to nurture both their teacher-self and their artist-self (Lichtenstein 2009). The research question was: can interactions between professional dance artists, teacher-artists (Mc Lean, 2009) and classroom dance teachers change classroom dance teachers’ self-perceptions? The research found that Artists in Residence projects provide up-skilling in situ for classroom dance teachers, and give credence to the act of art making for classroom dance teachers within their peer context, positively enhancing their self-image and promoting self-identification as ‘teacher-artists’ (Mc Lean, 2009). This project received an Artist in Residence Grant (an Australia Council for the Arts, Education Queensland and Queensland Arts Council partnership). The research findings were chosen for inclusion in the Queensland Performing Arts Complex program, Feet First: an invitation to dance, 2013 and selected for inclusion on the Creative Campus website, http://www.creative-campus.org.uk.

The effect of three different (-135°C) whole body cryotherapy exposure durations on elite rugby league players

Background: Whole body cryotherapy (WBC) is the therapeutic application of extreme cold air for a short duration. Minimal evidence is available for determining optimal exposure time. Purpose: To explore whether the length of WBC exposure induces differential changes in inflammatory markers, tissue oxygenation, skin and core temperature, thermal sensation and comfort. Method: This study was a randomised cross over design with participants acting as their own control. Fourteen male professional first team super league rugby players were exposed to 1, 2, and 3 minutes of WBC at -135°C. Testing took place the day after a competitive league fixture, each exposure separated by seven days. Results: No significant changes were found in the inflammatory cytokine interleukin six. Significant reductions (p<0.05) in deoxyhaemoglobin for gastrocnemius and vastus lateralis were found. In vastus lateralis significant reductions (p<0.05) in oxyhaemoglobin and tissue oxygenation index (p<0.05) were demonstrated. Significant reductions (p<0.05) in skin temperature were recorded. No significant changes were recorded in core temperature. Significant reductions (p<0.05) in thermal sensation and comfort were recorded. Conclusion: Three brief exposures to WBC separated by 1 week are not sufficient to induce physiological changes in IL-6 or core temperature. There are however significant changes in tissue oxyhaemoglobin, deoxyhaemoglobin, tissue oxygenation index, skin temperature and thermal sensation. We conclude that a 2 minute WBC exposure was the optimum exposure length at temperatures of -135°C and could be applied as the basis for future studies.

Reported consumption of takeaway food and its contribution to socioeconomic inequalities in body mass index

The aim of this study was to examine whether takeaway food consumption mediated (explained) the association between socioeconomic position and body mass index (BMI). A postal-survey was conducted among 1500 randomly selected adults aged between 25 and 64 years in Brisbane, Australia during 2009 (response rate 63.7%, N=903). BMI was calculated using self-reported weight and height. Participants reported usual takeaway food consumption, and these takeaway items were categorised into "healthy" and "less healthy" choices. Socioeconomic position was ascertained by education, household income, and occupation. The mean BMI was 27.1kg/m(2) for men and 25.7kg/m(2) for women. Among men, none of the socioeconomic measures were associated with BMI. In contrast, women with diploma/vocational education (β=2.12) and high school only (β=2.60), and those who were white-collar (β=1.55) and blue-collar employees (β=2.83) had significantly greater BMI compared with their more advantaged counterparts. However, household income was not associated with BMI. Among women, the consumption of "less healthy" takeaway food mediated BMI differences between the least and most educated, and between those employed in blue collar occupations and their higher status counterparts. Decreasing the consumption of "less healthy" takeaway options may reduce socioeconomic inequalities in overweight and obesity among women but not men.

Professionalizing Business Process Management : towards a Body of Knowledge for BPM

Business Process Management (BPM) is rapidly evolving as an established discipline. There are a number of efforts underway to formalize the various aspects of BPM practice; creating a formal Body of Knowledge (BoK) is one such effort. Bodies of knowledge are artifacts that have a proven track record for accelerating the professionalization of various disciplines. In order for this to succeed in BPM, it is vital to involve the broader business process community and derive a BoK that has essential characteristics that addresses the discipline’s needs. We argue for the necessity of a comprehensive BoK for the BPM domain, and present a core list of essential features to consider when developing a BoK based on preliminary empirical evidence. The paper identifies and critiques existing Bodies of Knowledge related to BPM, and firmly calls for an effort to develop a more accurate and sustainable BoK for BPM. An approach for this effort is presented with preliminary outcomes.

A preliminary study on assessing body burden of persistent organic pollutants (POPs) in infants through analysis of faeces

Most persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs), a range of polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs) are readily absorbed (via the ingestion and inhalation) and accumulate in fatty tissue, including adipose tissue and human milk [1]. Health effects related to exposure to these chemicals may include neurological effects, altered functioning of the nervous system and/or endocrine disruption [2-4]. The burden of environmental disease is recognized as much higher for children than adults, especially in young children under 5 years of age worldwide [5]. There is increased concern regarding the environmental impact on the health of children who have been disproportionately affected by environmental problems. For example they may be subjected to relatively higher exposure, have greater physiological susceptibility and/or suffer more extreme consequences due to growth [6-9]. It is therefore worthwhile to assess the correlation between burden of disease and exposure to xenobiotic chemical pollutants like POPs. Such assessment may provide guidance for legislative changes regarding chemical bans and give reliable advice to parents including lactating mothers.

Development and validation of anthropometric prediction equations for estimation of body fat in Indonesian men

Body composition of 292 males aged between 18 and 65 years was measured using the deuterium oxide dilution technique. Participants were divided into development (n=146) and cross-validation (n=146) groups. Stature, body weight, skinfold thickness at eight sites, girth at five sites, and bone breadth at four sites were measured and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) calculated. Equations were developed using multiple regression analyses with skinfolds, breadth and girth measures, BMI, and other indices as independent variables and percentage body fat (%BF) determined from deuterium dilution technique as the reference. All equations were then tested in the cross-validation group. Results from the reference method were also compared with existing prediction equations by Durnin and Womersley (1974), Davidson et al (2011), and Gurrici et al (1998). The proposed prediction equations were valid in our cross-validation samples with r=0.77- 0.86, bias 0.2-0.5%, and pure error 2.8-3.6%. The strongest was generated from skinfolds with r=0.83, SEE 3.7%, and AIC 377.2. The Durnin and Womersley (1974) and Davidson et al (2011) equations significantly (p<0.001) underestimated %BF by 1.0 and 6.9% respectively, whereas the Gurrici et al (1998) equation significantly (p<0.001) overestimated %BF by 3.3% in our cross-validation samples compared to the reference. Results suggest that the proposed prediction equations are useful in the estimation of %BF in Indonesian men.