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Background/Objectives:The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER) improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER attenuated compensatory responses associated with ER.Subjects/Methods:Fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the intervention (CON: N=23, 39.4±6.8 years, 111.1±9.1 kg, 34.3±3.0 kg m-2 ; INT: N=24, 39.8±9.5 years, 110.2±13.8 kg, 34.1±4.0 kg m-2 ). During ER, energy intake was equivalent to 67% of weight maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) were measured throughout the study.Results:For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: -624±557 kJ d-1 ; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: -360±502 vs CON: -749±498 kJ d-1 ; P<0.05).Conclusions:Greater weight and fat loss was achieved with intermittent ER. Interrupting ER with energy balance 'rest periods' may reduce compensatory metabolic responses and, in turn, improve weight loss efficiency.

Objective: We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention. Design: In all, 16 obese men and women (41±9 years; body mass index (BMI) 39±6 kg m −2 ) were investigated in energy balance before, after and twice during a 12-week very-low-energy diet(565–650 kcal per day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74%–87%). Body composition was measured by deuterium dilution and dual energy X-ray absorptiometry, and resting metabolic rate (RMR) was measured by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants 9.45 kcal per g FM and 1.13 kcal per g FFM. Predicted weight loss was calculated from the EDef using the ′7700 kcal kg −1 rule′. Results: Changes in weight (−18.6±5.0 kg), FM (−15.5±4.3 kg) and FFM (−3.1±1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39% to 94%. Relative EDef was correlated with the decrease in RMR ( R =0.70, P <0.01), and the decrease in RMR correlated with the difference between actual and expected weight loss ( R =0.51, P <0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of the predicted values. Conclusion: Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. Although lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic downregulation should not be discounted.

Objective: To determine the minimum number of days of dietary intake interviews required to reduce the effects of random error (day-to-day variability in dietary intake) when using the multiple-pass, multiple-day, 24-h recall method. Design: Cross-sectional study. Setting: University research department. Subjects: A total of 50 healthy non-smoking overweight and obese (body mass index=26-40 kg/m2) adult men and women aged 39-45 years completed the study. Participants were randomly selected from volunteers for a larger unrelated study. Interventions: Each participant completed 10, multiple-pass, 24-h recall interviews on randomly chosen days over 4 weeks. The minimum number of record days was determined for each macronutrient (carbohydrate, fat, protein) and energy, for each gender, to obtain a 'true' (unobservable) representative intake from reported (observed) dietary intakes. Results: The greatest number of days required to obtain a 'true' representative intake was 8 days. Carbohydrate intakes required the greatest number of days of dietary record among males (7 days), whereas protein required the greatest number of days among females (8 days) in this cohort. Sunday was the day of the week that showed greatest variability in macronutrient intakes. Protein (P<0.05) and fat (P<0.001) intakes were significantly more variable than carbohydrate on Sundays compared with weekdays, for both men and women. Conclusion: A logistically achievable 8 days of dietary intake interviews was sufficient to minimize the effect of random error when using the multiple-pass, 24-h recall dietary intake method. Sunday should be included among the dietary interview days to ensure a 'true' representation of macronutrient intakes. This method can be confidently applied to small cohort studies in which dietary intakes from different groups are to be compared or to investigations of associations between nutrient intakes and disease.

Objective: To measure adherence to a specific exercise prescription (1500 kcal week- 1) by objectively quantifying unsupervised exercise energy expenditure (ExEE) in obese women. Design: The 16-week lifestyle intervention consisted of weekly meetings with research staff and promotion of increased ExEE (1500 kcal week- 1) and a decreased dietary intake (- 500 kcal day- 1). Participants: Twenty-nine obese females (body mass index=36.85.0 kg m- 2, body fat=49.63.7% ) from a hospital-based lifestyle intervention were included in the analysis. Measurements: ExEE was estimated and monitored weekly using heart rate monitoring, and body composition was measured before and after the intervention by dual-energy X-ray absorptiometry. Results: Free-living adherence to the exercise prescription was variable and, on average, modest such that 14% achieved 1500 kcal week- 1, and the average weekly ExEE (768 kcal week- 1) represented 51.2% of the total amount prescribed. ExEE was correlated with changes in body weight (r=0.65, P<0.001) and fat mass (r=0.65, P<0.001). Achievement of a 5% weight loss target was dependent on the achievement of an ExEE level of 1000 kcal week- 1 (P<0.001). Exercise 'adherers' (>1000 kcal week- 1) lost more weight (- 9.9 vs - 4.1 kg), more fat mass (- 6.8 vs - 3.0 kg) and more waist circumference (- 9.8 vs - 5.6 cm) when compared to 'non-adherers' (<1000 kcal week- 1). Discussion: Exercise is an integral component of lifestyle interventions aimed at reducing obesity and its complications. However, without accurate and objective measures of ExEE, it is difficult for relationships between exercise and health outcomes to be elucidated. The present study suggests an alternative to self-report to increase the confidence with which conclusions are drawn regarding the role of exercise within lifestyle interventions.

Background/Objectives: To develop and cross-validate bioelectrical impedance analysis (BIA) prediction equations of total body water (TBW) and fat-free mass (FFM) for Asian pre-pubertal children from China, Lebanon, Malaysia, Philippines and Thailand. Subjects/Methods: Height, weight, age, gender, resistance and reactance measured by BIA were collected from 948 Asian children (492 boys and 456 girls) aged 8–10 years from the five countries. The deuterium dilution technique was used as the criterion method for the estimation of TBW and FFM. The BIA equations were developed using stepwise multiple regression analysis and cross-validated using the Bland–Altman approach. Results: The BIA prediction equation for the estimation of TBW was as follows: TBW=0.231 × height 2 /resistance+0.066 × height+0.188 × weight+0.128 × age+0.500 × sex−0.316 × Thais−4.574 ( R 2 =88.0%, root mean square error (RMSE)=1.3 kg), and for the estimation of FFM was as follows: FFM=0.299 × height 2 /resistance+0.086 × height+0.245 × weight+0.260 × age+0.901 × sex−0.415 × ethnicity (Thai ethnicity =1, others = 0)−6.952 ( R 2 =88.3%, RMSE=1.7 kg). No significant difference between measured and predicted values for the whole cross-validation sample was found. However, the prediction equation for estimation of TBW/FFM tended to overestimate TBW/FFM at lower levels whereas underestimate at higher levels of TBW/FFM. Accuracy of the general equation for TBW and FFM was also valid at each body mass index category. Conclusions: Ethnicity influences the relationship between BIA and body composition in Asian pre-pubertal children. The newly developed BIA prediction equations are valid for use in Asian pre-pubertal children.

Background Identification of bacterial pathogens is paramount for prompt and effective treatment of respiratory exacerbations in children with cystic fibrosis (CF). This can be a challenge in non-expectorating patients as reliability of cough swabs (CS) is poor. More recently, cough plates (CP) have been reported to give high yields in some series. The aim of the study was to ascertain their effectiveness compared to CS and to assess the impact of cough strength on efficacy of CP. Method Non-expectorating children with CF aged 3–16 years were recruited. Baseline data was recorded and peak cough flow measured. Specimens were obtained with CP and a cough swab in a randomised order and repeated at up to four clinic visits to obtain multiple measurements. Subjects completed a short questionnaire. Results Number of subjects was 95, mean age 8.8±4.1 years, 45 males. Mean baseline % predicted FEV1 was 90.8±18. In total, 324 sets of specimens were collected. Pathogens were isolated in 18.2% of CS and 8% of CP. Agreement between the two specimens occurred in only 5.5% of cases. CP isolated pathogens on six occasions when the CS was negative while 40 CS were positive with a corresponding negative CP. Cough strength increased with age, and there was a trend towards older children isolating more pathogens on CP. However, this was not statistically significant. The majority of subjects preferred the CP. Conclusions CP are less effective than CS in identifying respiratory pathogens in children with CF.

Background: When single-agent androgen deprivation therapy (ADT) is administered for locally advanced prostate cancer, men usually relapse within 1–2 years with more malignant castrate-resistant disease. The reason for this is currently unknown. We now hypothesise that an initial treatment response that increases tumour hypoxia drives selection of more malignant tumours. Methods: The LNCaP prostate tumour xenografts were analysed for physiological (oxygen and vasculature) and genetic (PCR array) changes during longitudinal treatment with ADT (bicalutamide, 6 or 2 mg kg −1 daily for 28 days). Results: Bicalutamide caused an immediate (within 24 h) dose-dependent fall in oxygenation in LNCaP-luc prostate tumours with a nadir of ≤0.1% oxygen within 3–7 days; this was attributed to a significant loss of tumour microvessels (window chamber study). The hypoxic nadir persisted for 10–14 days. During the next 7 days, tumours regrew, oxygenation improved and the vasculature recovered; this was inhibited by the VEGF inhibitor B20.4.1.1. Gene expression over 28 days showed marked fluctuations consistent with the physiological changes. Accompanying the angiogenic burst (day 21) was a particularly striking increase in expression of genes associated with epithelial-to-mesenchymal transition (EMT). In particular, insulin-like growth factor 1 (IGF-1) showed increases in mRNA and protein expression. Conclusions: Hypoxic stress caused by ADT promotes EMT, providing a mechanism for the cause of malignant progression in prostate cancer.

Objective: To investigate the variability in isotopic equilibrium time under field conditions, and the impact of this variability on estimates of total body water (TBW) and body composition. Design and Setting: Following collection of a fasting baseline urine sample, 10 women and 10 men were dosed with deuterium oxide (0.05 g/kg body weight). Urine samples were collected every hour for 8 h. The samples were analysed using isotope ratio mass spectrometry. Time to equilibration was determined using three commonly employed data analysis approaches. Results: Isotopic equilibrium was reached by 50, 80 and 100% of participants at 4, 6 and 8 h, respectively. The mean group equilibration determined using the three different plateau determination methods were 4.81.5, 3.80.8 and 4.91.4 h. Isotopic enrichment, TBW, and percent body fat estimates differed between early (3-5 h), but not later sampling times (5-8 h). Conclusion: Although the three different plateau determination approaches resulted in differences in equilibration time, all suggest that sampling at 6 h or later will decrease the likelihood of error in body composition estimates resultant from incomplete isotopic equilibration in a small proportion of individuals.

Summary Objective and methods Finding effective solutions to curb the obesity epidemic is a great global public health challenge. The need for long‐term follow‐up necessitates weight loss trials conducted in real‐world settings, outside the confines of tightly controlled laboratory or clinic conditions. Given the complexity of eating behaviour and the food supply, this makes the process of designing a practical dietary intervention that stands up to scientific rigor difficult. Detailed information about the dietary intervention itself, as well as the process of developing the final intervention and its underlying rationale, is rarely reported in scientific weight management publications but is valuable and essential for translating research into practice. Thus, this paper describes the design process and underlying rationale behind the dietary interventions in an exemplar weight loss trial – the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity). This trial assesses the long‐term effects of fast versus slow weight loss on adiposity, fat free mass, muscle strength and bone density in women with obesity (body mass index 30–40 kg m−2) that are 45–65 years of age, postmenopausal and sedentary. Results and conclusions This paper is intended as a resource for researchers and/or clinicians to illustrate how theoretical values based on a hypothesis can be translated into a dietary weight loss intervention to be used in free‐living women of varying sizes.

Despite increased evidence for the importance of lifestyle modification, physical activity and diet in diabetes prevention and management, habitual physical activity levels have declined in recent decades in China and India. Further, other risk factors for type 2 diabetes, including overweight, obesity and physical inactivity, have also worsened. Here we present evidence for the importance of physical activity and exercise in the amelioration of type 2 diabetes and propose a novel approach to address the challenge of improving lifestyle behaviors in China and India—Movement is Medicine and a P4 (predictive, preventive, personalized and participatory) approach.