Realizing acoustic qubit analogues with nonlinearly tunable phi-bits in externally driven coupled acoustic waveguides.

Using experiments and theory, we investigate the behavior of nonlinear acoustic modes in a physical system composed of an array of three coupled acoustic waveguides, two of which are externally driven with two different frequencies. Nonlinear modes with frequency given by linear combinations of the driving frequencies are realizations of so-called logical phi-bits. A phi-bit is a two-state degree of freedom of an acoustic wave, which can be in a coherent superposition of states with complex amplitude coefficients, i.e., a qubit analogue. We demonstrate experimentally that phi-bit modes are supported in the array of waveguides. Using perturbation theory, we show that phi-bits may result from the intrinsic nonlinearity of the material used to couple the waveguides. We have also isolated possible effects on phi-bit states associated with the systems' electronics, transducers and ultrasonic coupling agents used to probe the array and that may introduce extrinsic nonlinearities. These extrinsic effects are shown to be easily separable from the intrinsic behavior. The intrinsic behavior includes sharp jumps in phi-bit phases occurring over very narrow ranges of driving frequency. These jumps may also exhibit hysteretic behavior dependent on the direction of driving frequency tuning. The intrinsic states of phi-bits and multiple nonlinearly correlated phi-bits may serve as foundation for robust and practical quantum-analogue information technologies.

Evidence-Based Medicine as a Tool for Undergraduate Probability and Statistics Education.

Most students have difficulty reasoning about chance events, and misconceptions regarding probability can persist or even strengthen following traditional instruction. Many biostatistics classes sidestep this problem by prioritizing exploratory data analysis over probability. However, probability itself, in addition to statistics, is essential both to the biology curriculum and to informed decision making in daily life. One area in which probability is particularly important is medicine. Given the preponderance of pre health students, in addition to more general interest in medicine, we capitalized on students' intrinsic motivation in this area to teach both probability and statistics. We use the randomized controlled trial as the centerpiece of the course, because it exemplifies the most salient features of the scientific method, and the application of critical thinking to medicine. The other two pillars of the course are biomedical applications of Bayes' theorem and science and society content. Backward design from these three overarching aims was used to select appropriate probability and statistics content, with a focus on eliciting and countering previously documented misconceptions in their medical context. Pretest/posttest assessments using the Quantitative Reasoning Quotient and Attitudes Toward Statistics instruments are positive, bucking several negative trends previously reported in statistics education.

Visualizing Network Traffic to Understand the Performance of Massively Parallel Simulations.

The performance of massively parallel applications is often heavily impacted by the cost of communication among compute nodes. However, determining how to best use the network is a formidable task, made challenging by the ever increasing size and complexity of modern supercomputers. This paper applies visualization techniques to aid parallel application developers in understanding the network activity by enabling a detailed exploration of the flow of packets through the hardware interconnect. In order to visualize this large and complex data, we employ two linked views of the hardware network. The first is a 2D view, that represents the network structure as one of several simplified planar projections. This view is designed to allow a user to easily identify trends and patterns in the network traffic. The second is a 3D view that augments the 2D view by preserving the physical network topology and providing a context that is familiar to the application developers. Using the massively parallel multi-physics code pF3D as a case study, we demonstrate that our tool provides valuable insight that we use to explain and optimize pF3D's performance on an IBM Blue Gene/P system.

Evaluation of the Accuracy of a Triaxial Accelerometer Embedded into a Cell Phone Platform for Measuring Physical Activity.

BACKGROUND: Physical activity is important in health and weight management. Several cell phone platforms integrate an accelerometer onto the motherboard. Here we tested the validity of the cell phone accelerometer to assess physical activity in a controlled laboratory setting. METHODS: 31 subjects wore the cell phone on their waist along with the validated Physical Activity Monitoring System (PAMS) with different body postures and during graded walking. Energy expenditure was measured using indirect calorimetry. 11 subjects also wore the iPhone at different locations such as arm, hand, pant pocket, etc. RESULTS: The cell phone accelerometer was accurate and precise compared to the PAMS, with an intra-class correlation coefficient (r2> 0.98). The cell phone accelerometer showed excellent sequential increases with increased in walking velocity and energy expenditure (r2>0.9). CONCLUSION: An accelerometer embedded into a cell phone was accurate and reliable in measuring and quantifying physical activity in the laboratory setting. Data from free-living users shows promise for deployment of a comprehensive integrated physical activity promoting and weight loss platform using such mobile technologies.

Feasibility of a walking workstation to increase daily walking.

OBJECTIVE: The number of calories expended in the workplace has declined significantly in the past 75 years. A walking workstation that allows workers to walk while they work has the potential to increase caloric expenditure. We evaluated whether employees can and will use walking workstations while performing their jobs. METHODS AND PROCEDURES: We studied nurses, clinical assistants, secretaries and appointment secretaries using the StepWatch Activity Monitor System (which accurately measures steps taken at slow speeds) while performing their job functions in their usual fashion and while using the walking workstation. RESULTS: Subjects increased the number of steps taken during the workday by 2000 steps per day (p<0.05). This was equivalent to an increase in caloric expenditure of 100 kcal/day. Subjects reported that they enjoyed using the workstation, that it could be used in the actual work arena and that, if available, they would use it. DISCUSSION: Walking workstations have the potential for promoting physical activity and facilitating weight loss. Several subjects in this study expended more than 200 extra calories daily using such a system. Further trials are indicated.

Central neural and endocrine mechanisms of non-exercise activity thermogenesis and their potential impact on obesity.

The rise in obesity is associated with a decline in the amount of physical activity in which people engage. The energy expended through everyday non-exercise activity, called non-exercise activity thermogenesis (NEAT), has a considerable potential impact on energy balance and weight gain. Comparatively little attention has been paid to the central mechanisms of energy expenditure and how decreases in NEAT might contribute to obesity. In this review, we first examine the sensory and endocrine mechanisms through which energy availability and energy balance are detected that may influence NEAT. Second, we describe the neural pathways that integrate these signals. Lastly, we consider the effector mechanisms that modulate NEAT through the alteration of activity levels as well as through changes in the energy efficiency of movement. Systems that regulate NEAT according to energy balance may be linked to neural circuits that modulate sleep, addiction and the stress response. The neural and endocrine systems that control NEAT are potential targets for the treatment of obesity.

Gait and balance of transfemoral amputees using passive mechanical and microprocessor-controlled prosthetic knees.

BACKGROUND: Microprocessor-controlled knee joints appeared on the market a decade ago. These joints are more sophisticated and more expensive than mechanical ones. The literature is contradictory regarding changes in gait and balance when using these sophisticated devices. METHODS: This study employed a crossover design to assess the comparative performance of a passive mechanical knee prosthesis compared to a microprocessor-controlled knee joint in 15 subjects with an above-knee amputation. Objective measurements of gait and balance were obtained. RESULTS: Subjects demonstrated significantly improved gait characteristics after receiving the microprocessor-controlled prosthetic knee joint (p<0.01). Improvements in gait were a transition from a hyperextended knee to a flexed knee during loading response which resulted in a change from an internal knee flexor moment to a knee extensor moment. The participants' balance also improved (p<0.01). All conditions of the Sensory Organization Test (SOT) demonstrated improvements in equilibrium score. The composite score also increased. CONCLUSIONS: Transfemoral amputees using a microprocessor-controlled knee have significant improvements in gait and balance.

Nonexercise activity thermogenesis--liberating the life-force.

Obesity occurs when energy intake exceeds energy expenditure over a protracted period of time. The energy expenditure associated with everyday activity is called NEAT (Nonexercise activity thermogenesis). NEAT varies between two people of similar size by 2000 kcal day(-1) because of people's different occupations and leisure-time activities. Data support the central hypothesis that NEAT is pivotal in the regulation of human energy expenditure and body weight regulation and that NEAT is important for understanding the cause and effective treatment for obesity.

International survey of seat belt use exemptions.

BACKGROUND: Substantial evidence of seatbelt efficacy has been shown by several studies, and it is widely recommended that motor vehicle occupants use properly fitted seat belts. However, some (but a heretofore unknown number of) countries with national seat belt laws permit various exemptions which may lower use rates. The aim of this study was to survey the variety of exemptions to national seat belt laws. METHODS: This investigation relied on identifying respondents from national traffic safety agencies, other governmental and non-governmental organizations, Internet searches, personal contacts, and other sources. Questionnaires were deployed through a web based survey supplemented by email and postal versions. RESULTS: Responses were received from 30 countries of which 28 (93.7%) had a national seat belt law. About two thirds (63.7%) of the 28 national laws applied to both front and back seat passengers. The leading exemption types included vehicles made before a certain year (n = 13), antique vehicles (n = 12), military vehicles (n = 11), buses (n = 9), and emergency vehicles (n = 8). Most responding countries reported one or more specific categories of individuals as exempt including those with medical exemptions (n = 20), taxi drivers (n = 11), police (n = 9), emergency medical personnel (n = 8), physically disabled people (n = 6), and pregnant women (n = 6). Out of 26 responses to the question regarding current level of enforcement, 42.3% felt enforcement was "very good or good" and 57.7% characterized it as "fair or poor". CONCLUSIONS: This study represents one of the largest international traffic law surveys reported. Most national seatbelt laws offer perilous exemptions to a broad array of vehicle types and road user groups. These findings, coupled with concern over the level of enforcement in the majority of countries surveyed, suggest that international road safety efforts have a long way to go to improve coverage and enforcement of national seat belt laws.

Neuromedin U in the paraventricular and arcuate hypothalamic nuclei increases non-exercise activity thermogenesis.

Brain neuromedin U (NMU) has been associated with the regulation of both energy intake and expenditure. We hypothesized that NMU induces changes in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) through its actions on hypothalamic nuclei. We applied increasing doses of NMU directly to the paraventricular (PVN) and arcuate hypothalamic nuclei using chronic unilateral guide cannulae. In both nuclei, NMU significantly and dose-dependently increased physical activity and NEAT. Moreover, NMU increased physical activity and NEAT during the first hour of the dark phase, indicating that the reduction of sleep is unlikely to account for the increased physical activity seen with NMU treatment. As a positive control, we demonstrated that paraventricular NMU also significantly decreased food intake, as well as body weight. These data demonstrate that NMU is positively associated with NEAT through its actions in the PVN and arcuate nucleus. In co-ordination with its suppressive effects on feeding, the NEAT-activating effects of NMU make it a potential candidate in the combat of obesity.

Orexin A mediation of time spent moving in rats: neural mechanisms.

The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0-1000 pmol) into three orexin projection sites in male Sprague-Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A-induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity.

Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats.

Selectively-bred obesity-resistant [diet resistant (DR)] rats weigh less than obesity-prone [diet-induced obese (DIO)] rats, despite comparable daily caloric intake, suggesting phenotypic energy expenditure differences. Human data suggest that obesity is maintained by reduced ambulatory or spontaneous physical activity (SPA). The neuropeptide orexin A robustly stimulates SPA. We hypothesized that DR rats have greater: 1) basal SPA, 2) orexin A-induced SPA, and 3) preproorexin, orexin 1 and 2 receptor (OX1R and OX2R) mRNA, compared with DIO rats. A group of age-matched out-bred Sprague-Dawley rats were used as additional controls for the behavioral studies. DIO, DR, and Sprague-Dawley rats with dorsal-rostral lateral hypothalamic (rLHa) cannulas were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 microl). SPA and food intake were measured for 2 h after injection. Preproorexin, OX1R and OX2R mRNA in the rLHa, and whole hypothalamus were measured by real-time RT-PCR. Orexin A significantly stimulated feeding in all rats. Orexin A-induced SPA was significantly greater in DR and Sprague-Dawley rats than in DIO rats. Two-mo-old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-mo-old DR rats had elevated OX1R and OX2R mRNA compared with DIO rats, although this increase was significant for OX2R only at this age. Thus DR rats show elevated basal and orexin A-induced SPA associated with increased OX1R and OX2R gene expression, suggesting that differences in orexin A signaling through OX1R and OX2R may mediate DIO and DR phenotypes.

NEAT--non-exercise activity thermogenesis--egocentric & geocentric environmental factors vs. biological regulation.

Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all physical activities other than volitional sporting-like exercise. NEAT includes all those activities that render us vibrant, unique and independent beings such as going to work, playing guitar, toe-tapping and dancing. The factors that account for the 2000 kcal day(-1) variability of NEAT can be categorized as environmental or biological. The environmental determinants of NEAT can be view using one of two models. In the egocentric model we consider a single person as the focus, e.g. 'my job'. In the geocentric model we consider the 'environment' as the focus, e.g. well-lit and safe walk ways. These models provide us with a theoretical framework to understand NEAT and how best to intervene to promote NEAT. As well as environmental effectors of NEAT, there are also biological regulatory mechanisms that enable us to account for three-quarters of the biological variance in susceptibility and resistance to fat gain with human over-feeding. NEAT is likely to be regulated through a central mechanism that integrates NEAT with energy intake and energy stores so that NEAT is activated with over-feeding and suppressed with under-feeding. In conclusion, NEAT is likely to serve as a crucial thermoregulatory switch between energy storage and dissipation that is biologically regulated and influenced, and perhaps over-ridden, by environment. Deciphering the role of NEAT may lead to a better understanding of the pathogenesis, prevention and treatment of obesity.

Differential effects of adrenocorticotropic hormone on human and mouse adipose tissue.

Adrenocorticotropic hormone (ACTH) induces lipolysis in a dose-dependent fashion in rodent adipose tissue and adipocytes in vitro. The role of ACTH on lipolysis in human adipose tissue is less clear, however. In this study, we address the hypothesis that ACTH induces lipolysis in human adipose tissue. We used ex vivo organ culture to examine lipolysis in human and mouse adipose tissue. Adipose tissue fragments suspended in culture medium and human ACTH, isoproterenol (positive control), or insulin (negative control) was added in varying concentrations. Lipolysis was measured using glycerol appearance. ACTH receptor mRNA expression was assessed using reverse-transcription polymerase chain reaction (RT-PCR). In mouse adipose tissue, ACTH induced lipolysis in dose-dependent manner; 100 pmol/l ACTH induced 67+/-19% of isoproterenol-stimulated lipolysis and 500 pmol/l ACTH: 86+/-13%. In contrast, human adipose tissue shared no significant response to 100 pmol/l ACTH; ACTH was associated with 9+/-6% and 500 pmol/l of ACTH, 8+/-6% of isoproterenol-stimulated lipolysis. ACTH receptor mRNA was present in mouse adipose tissue, but undetectable in human adipose tissue. These results suggest lipolysis regulation differs between human and mouse adipose tissue in response to ACTH.

Is there a role for gastric accommodation and satiety in asymptomatic obese people?

OBJECTIVE: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non-obese asymptomatic subjects. RESEARCH METHODS AND PROCEDURES: In 13 obese (body mass index [BMI] > or = 30 kg/m(2); mean BMI, 37.0 +/- 4.9 kg/m(2)) and 19 non-obese control subjects (BMI < 30 kg/m(2); mean BMI, 26.2 +/- 2.9 kg/m(2)), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. RESULTS: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. DISCUSSION: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m(2)) did not show either increased postprandial gastric accommodation or reduced satiety. These data suggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.

Validation of the Tracmor triaxial accelerometer system for walking.

PURPOSE: Walking is likely to contribute substantially to nonexercise activity thermogenesis. The Tracmor triaxial accelerometer system (Maastricht, The Netherlands) is the most widely validated system for detecting body movement in free-living subjects. The aim of this study was to validate the Tracmor triaxial accelerometer system for estimating the energy expenditure of walking. METHODS: Experiments were conducted in healthy subjects. First, baseline variability for Tracmor output was determined for subjects standing still. Second, Tracmor output was compared for walking on a treadmill and on level ground. Third, both Tracmor output and energy expenditure were compared for walking on a treadmill and walking on level ground. Finally, the effect of gradient on Tracmor output and energy expenditure was compared for subjects walking on a treadmill. RESULTS: The data demonstrated excellent reproducibility for comparing Tracmor output for standing (CV < 2%). There were excellent log-linear relationships between velocity and Tracmor output walking on a treadmill (r = 0.998) and on level ground (r = 0.999). Tracmor output and the energy expenditure of walking were inseparable for the two modalities of walking. However, the variance in response was such that to reliably derive the relationship between Tracmor output and energy expenditure, separate regression equations are needed for each subject. Finally, the Tracmor accelerometer did not detect the increased energy expenditure of walking that occurs as gradient increases. CONCLUSION: The Tracmor triaxial accelerometer provides reproducible and reliable data on the body motion associated with walking regardless of whether a subject walks on a treadmill or level ground. Tracmor units can be used to predict the energetic cost of walking provided that separate regression equations are derived for each subject to convert Tracmor output to energy expenditure.

Relationship between duration of pain and secondary signs of obstruction of the urinary tract on unenhanced helical CT.

OBJECTIVE: The objective of this study was to investigate the relationship between duration of flank pain and the frequency of secondary signs of ureteral obstruction on unenhanced helical CT. SUBJECTS AND METHODS: The duration of flank pain was prospectively determined in 227 consecutive patients diagnosed with acute ureterolithiasis on unenhanced helical CT. These CT studies were evaluated for the presence or absence of perinephric stranding, ureteral dilatation, perinephric fluid, collecting system dilatation, periureteral stranding, and nephromegaly. The frequency of each sign was determined as a function of the duration of pain. RESULTS: The frequency of moderate or severe perinephric stranding increased from 5% at 1--2 hr to 51% at 7--8 hr (p < 0.001); ureteral dilatation increased from 84% at 1--2 hr to 97% at more than 8 hr (p < 0.03); moderate or severe perinephric fluid increased from 0% at 1--2 hr to 22% at 3--4 hr (p < 0.03); collecting system dilatation increased from 68% at 1--2 hr to 89% at 7-8 hr (p < 0.03); periureteral stranding increased from 35% at 1--2 hr to 76% at 7--8 hr (p < 0.004); and nephromegaly increased from 40% at 1--2 hr to 54% at 7--8 hr (p < 0.36). CONCLUSION: All CT secondary signs of ureteral obstruction except nephromegaly showed a significant increase in frequency as duration of flank pain increased. This observation may explain why the CT studies of some patients with acute ureterolithiasis show negative findings for some or all CT secondary signs of obstruction. Therefore, knowledge of the duration of pain is important when interpreting unenhanced CT studies in patients with acute ureterolithiasis.

Energy expenditure of nonexercise activity.

BACKGROUND: We found recently that changes in nonexercise activity thermogenesis (NEAT) mediate resistance to weight gain with overfeeding in sedentary adults. A potentially important, yet seldom investigated, component of NEAT is the energy expenditure of fidgeting-like activities. OBJECTIVE: Our goal was to measure changes in energy expenditure with fidgeting-like activities. DESIGN: Energy expenditure was measured in 24 subjects (17 women and 7 men x+/- SD body weight: 76 +/- 21 kg) while recumbent at rest, sitting motionless, standing motionless, partaking of self-selected fidgeting-like movements while seated and while standing, and walking on a treadmill at 1.6, 3.2, and 4.8 km/h (1, 2, and 3 mph). Measurements were performed by using a high-precision, indirect calorimeter connected to the subject via a transparent, lightweight facemask that enabled almost unrestricted movement. RESULTS: Compared with metabolic rate in the supine position (5.4 +/- 1.5 kJ/min), energy expenditure increased while sitting motionless by 4 +/- 6%, while fidgeting while seated by 54 +/- 29% (P: < 0.0001), while standing motionless by 13 +/- 8% (P: < 0.0001), while fidgeting while standing by 94 +/- 38% (P: < 0.0001), while walking at 1.6 km/h by 154 +/- 38% (P: < 0.0001), while walking at 3.2 km/h by 202 +/- 45% (P: < 0.0001), and while walking at 4.8 km/h by 292 +/- 81% (P: < 0.0001). There was a significant, positive correlation between changes in energy expenditure and body weight for fidgeting-like activities while standing (r = 0.43, P: = 0.02) but not while seated. CONCLUSIONS: There is marked variance between subjects in the energy expenditure associated with self-selected fidgeting-like activities. The thermogenic potential of fidgeting-like and low-grade activities is sufficiently great to substantively contribute to energy balance.

Body composition and resting energy expenditure in humans: role of fat, fat-free mass and extracellular fluid.

OBJECTIVE: The objective of this study was to determine whether there are independent effects of extracellular fluid volume (ECF) and fat mass (FM) on resting energy expenditure (REE) relative to fat-free mass (FFM) in adult men and women. METHODS: Multiple linear regression analysis was used to relate REE, as determined by indirect calorimetry, to FFM and FM (measured using dual energy X-ray absorptiometry) and ECF (measured using bromide space and/or the radiosulfate washout space) in 153 women and 100 men with varying amounts of body fat. RESULTS: REE correlated significantly with FFM and FM in women (r=0.65 and r=0.63, both P<0.001) and men (r=0.62 and r=0.48, both P<0.001, FFM and FM, respectively). In a multiple linear regression analysis FFM, FM and age significantly contributed to the ability to predict REE in both genders. The models that were derived were not significantly different between women and men. In women the contribution to REE from FM was easier to detect when FM was greater. Adjustment of FFM for ECF did not improve the relationship between FFM and REE. CONCLUSIONS: FFM, FM and age are significant, independent predictors of REE in both men and women. Adjustment of FFM for ECF does not improve the ability of FFM to predict REE, which suggests that ECF is a highly integrated component of FFM in healthy adults. Expressing REE relative to FFM alone will introduce errors when lean and obese populations are compared.