53 research outputs found
An integrative paradigm to impart quality to correlative science
Correlative studies are a primary mechanism through which insights can be obtained about the bioactivity and potential efficacy of candidate therapeutics evaluated in early-stage clinical trials. Accordingly, well designed and performed early-stage correlative studies have the potential to strongly influence further clinical development of candidate therapeutic agents, and correlative data obtained from early stage trials has the potential to provide important guidance on the design and ultimate successful evaluation of products in later stage trials, particularly in the context of emerging clinical trial paradigms such as adaptive trial design
Assessing Physical Activity and its Relationship to Cardiovascular Risk Factors: NHANES 2003-2006
Estimates of adherence and error analysis of physical activity data collected via accelerometry in a large study of free-living adults
<p>Abstract</p> <p>Background</p> <p>Activity monitors (AM) are small, electronic devices used to quantify the amount and intensity of physical activity (PA). Unfortunately, it has been demonstrated that data loss that occurs when AMs are not worn by subjects (removals during sleeping and waking hours) tend to result in biased estimates of PA and total energy expenditure (TEE). No study has reported the degree of data loss in a large study of adults, and/or the degree to which the estimates of PA and TEE are affected. Also, no study in adults has proposed a methodology to minimize the effects of AM removals.</p> <p>Methods</p> <p>Adherence estimates were generated from a pool of 524 women and men that wore AMs for 13 – 15 consecutive days. To simulate the effect of data loss due to AM removal, a reference dataset was first compiled from a subset consisting of 35 highly adherent subjects (24 HR; minimum of 20 hrs/day for seven consecutive days). AM removals were then simulated during sleep and between one and ten waking hours using this 24 HR dataset. Differences in the mean values for PA and TEE between the 24 HR reference dataset and the different simulations were compared using paired <it>t</it>-tests and/or coefficients of variation.</p> <p>Results</p> <p>The estimated average adherence of the pool of 524 subjects was 15.8 ± 3.4 hrs/day for approximately 11.7 ± 2.0 days. Simulated data loss due to AM removals during sleeping hours in the 24 HR database (n = 35), resulted in biased estimates of PA (p < 0.05), but not TEE. Losing as little as one hour of data from the 24 HR dataset during waking hours results in significant biases (p < 0.0001) and variability (coefficients of variation between 7 and 21%) in the estimates of PA. Inserting a constant value for sleep and imputing estimates for missing data during waking hours significantly improved the estimates of PA.</p> <p>Conclusion</p> <p>Although estimated adherence was good, measurements of PA can be improved by relatively simple imputation of missing AM data.</p
Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition
Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested
Energy compensation and adiposity in humans
Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity
A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment
The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues
Daily energy expenditure through the human life course
Total daily energy expenditure (“total expenditure”) reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass–adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span
Targeting cancer stem cells by using chimeric antigen receptor-modified T cells: a potential and curable approach for cancer treatment
Human total, basal and activity energy expenditures are independent of ambient environmental temperature
Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures
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