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1.
Nature ; 555(7698): 599-603, 2018 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-29443961

RESUMEN

Electron spins in silicon quantum dots are attractive systems for quantum computing owing to their long coherence times and the promise of rapid scaling of the number of dots in a system using semiconductor fabrication techniques. Although nearest-neighbour exchange coupling of two spins has been demonstrated, the interaction of spins via microwave-frequency photons could enable long-distance spin-spin coupling and connections between arbitrary pairs of qubits ('all-to-all' connectivity) in a spin-based quantum processor. Realizing coherent spin-photon coupling is challenging because of the small magnetic-dipole moment of a single spin, which limits magnetic-dipole coupling rates to less than 1 kilohertz. Here we demonstrate strong coupling between a single spin in silicon and a single microwave-frequency photon, with spin-photon coupling rates of more than 10 megahertz. The mechanism that enables the coherent spin-photon interactions is based on spin-charge hybridization in the presence of a magnetic-field gradient. In addition to spin-photon coupling, we demonstrate coherent control and dispersive readout of a single spin. These results open up a direct path to entangling single spins using microwave-frequency photons.

2.
J Appl Biomech ; 40(2): 155-165, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38016463

RESUMEN

Biomechanics as a discipline is ideally placed to increase awareness and participation of girls and women in science, technology, engineering, and mathematics. A nationwide Biomechanics and Research Innovation Challenge (BRInC) centered on mentoring and role modeling was developed to engage high school girls (mentees) and early-mid-career women (mentors) in the field of biomechanics through the completion of a 100-day research and/or innovation project. This manuscript describes the development, implementation, and uptake of the inaugural BRInC program and synthesizes the research and innovation projects undertaken, providing a framework for adoption of this program within the global biomechanics community. Eighty-seven high school girls in years 9 and 10 (age range: 14-16 y) were mentored in teams (n = 17) by women in biomechanics (n = 24). Using a design thinking approach, teams generated solutions to biomechanics-based problem(s)/research question(s). Eight key reflections on program strengths, as well as areas for improvement and planned changes for future iterations of the BRInC program, are outlined. These key reflections highlight the innovation, impact, and scalability of the program; the importance of a program framework and effective communication tools; and implementation of strategies to sustain the program as well as the importance of diversity and building a sense of community.


Asunto(s)
Tutoría , Humanos , Femenino , Adolescente , Fenómenos Biomecánicos , Mentores
3.
J Exp Biol ; 226(7)2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-37021681

RESUMEN

Among terrestrial mammals, the largest, the 3 tonne African elephant, is one-million times heavier than the smallest, the 3 g pygmy shrew. Body mass is the most obvious and arguably the most fundamental characteristic of an animal, impacting many important attributes of its life history and biology. Although evolution may guide animals to different sizes, shapes, energetic profiles or ecological niches, it is the laws of physics that limit biological processes and, in turn, affect how animals interact with their environment. Consideration of scaling helps us to understand why elephants are not merely scaled-up shrews, but rather have modified body proportions, posture and locomotor style to mitigate the consequences of their large size. Scaling offers a quantitative lens into how biological features vary compared with predictions based on physical laws. In this Review, we provide an introduction to scaling and its historical context, focusing on two fields that are strongly represented in experimental biology: physiology and biomechanics. We show how scaling has been used to explore metabolic energy use with changes in body size. We discuss the musculoskeletal and biomechanical adaptations that animals use to mitigate the consequences of size, and provide insights into the scaling of mechanical and energetic demands of animal locomotion. For each field, we discuss empirical measurements, fundamental scaling theories and the importance of considering phylogenetic relationships when performing scaling analyses. Finally, we provide forward-looking perspectives focused on improving our understanding of the diversity of form and function in relation to size.


Asunto(s)
Locomoción , Mamíferos , Animales , Fenómenos Biomecánicos , Filogenia , Locomoción/fisiología , Tamaño Corporal , Mamíferos/fisiología
4.
J Anat ; 240(1): 131-144, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34411299

RESUMEN

Assessment of regional muscle architecture is primarily done through the study of animals, human cadavers, or using b-mode ultrasound imaging. However, there remain several limitations to how well such measurements represent in vivo human whole muscle architecture. In this study, we developed an approach using diffusion tensor imaging and magnetic resonance imaging to quantify muscle fibre lengths in different muscle regions along a muscle's length and width. We first tested the between-day reliability of regional measurements of fibre lengths in the medial (MG) and lateral gastrocnemius (LG) and found good reliability for these measurements (intraclass correlation coefficient [ICC] = 0.79 and ICC = 0.84, respectively). We then applied this approach to a group of 32 participants including males (n = 18), females (n = 14), young (24 ± 4 years) and older (70 ± 2 years) adults. We assessed the differences in regional muscle fibre lengths between different muscle regions and between individuals. Additionally, we compared regional muscle fibre lengths between sexes, age groups, and muscles. We found substantial variability in fibre lengths between different regions within the same muscle and between the MG and the LG across individuals. At the group level, we found no difference in mean muscle fibre length between males and females, nor between young and older adults, or between the MG and the LG. The high variability in muscle fibre lengths between different regions within the same muscle, possibly expands the functional versatility of the muscle for different task requirements. The high variability between individuals supports the use of subject-specific measurements of muscle fibre lengths when evaluating muscle function.


Asunto(s)
Imagen de Difusión Tensora , Músculo Esquelético , Animales , Imagen de Difusión Tensora/métodos , Femenino , Imagen por Resonancia Magnética , Masculino , Fibras Musculares Esqueléticas , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiología , Reproducibilidad de los Resultados
5.
J Exp Biol ; 225(Suppl_1)2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35258618

RESUMEN

A considerable biomechanical challenge faces larger terrestrial animals as the demands of body support scale with body mass (Mb), while muscle force capacity is proportional to muscle cross-sectional area, which scales with Mb2/3. How muscles adjust to this challenge might be best understood by examining varanids, which vary by five orders of magnitude in size without substantial changes in posture or body proportions. Muscle mass, fascicle length and physiological cross-sectional area all scale with positive allometry, but it remains unclear, however, how muscles become larger in this clade. Do larger varanids have more muscle fibres, or does individual fibre cross-sectional area (fCSA) increase? It is also unknown if larger animals compensate by increasing the proportion of fast-twitch (higher glycogen concentration) fibres, which can produce higher force per unit area than slow-twitch fibres. We investigated muscle fibre area and glycogen concentration in hindlimb muscles from varanids ranging from 105 g to 40,000 g. We found that fCSA increased with modest positive scaling against body mass (Mb0.197) among all our samples, and ∝Mb0.278 among a subset of our data consisting of never-frozen samples only. The proportion of low-glycogen fibres decreased significantly in some muscles but not others. We compared our results with the scaling of fCSA in different groups. Considering species means, fCSA scaled more steeply in invertebrates (∝Mb0.575), fish (∝Mb0.347) and other reptiles (∝Mb0.308) compared with varanids (∝Mb0.267), which had a slightly higher scaling exponent than birds (∝Mb0.134) and mammals (∝Mb0.122). This suggests that, while fCSA generally increases with body size, the extent of this scaling is taxon specific, and may relate to broad differences in locomotor function, metabolism and habitat between different clades.


Asunto(s)
Glucógeno , Lagartos , Animales , Tamaño Corporal , Miembro Posterior , Mamíferos , Fibras Musculares Esqueléticas , Músculo Esquelético/fisiología
6.
Proc Biol Sci ; 288(1947): 20210201, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33726594

RESUMEN

In our everyday lives, we negotiate complex and unpredictable environments. Yet, much of our knowledge regarding locomotion has come from studies conducted under steady-state conditions. We have previously shown that humans rely on the ankle joint to absorb energy and recover from perturbations; however, the muscle-tendon unit (MTU) behaviour and motor control strategies that accompany these joint-level responses are not yet understood. In this study, we determined how neuromuscular control and plantar flexor MTU dynamics are modulated to maintain stability during unexpected vertical perturbations. Participants performed steady-state hopping and, at an unknown time, we elicited an unexpected perturbation via rapid removal of a platform. In addition to kinematics and kinetics, we measured gastrocnemius and soleus muscle activations using electromyography and in vivo fascicle dynamics using B-mode ultrasound. Here, we show that an unexpected drop in ground height introduces an automatic phase shift in the timing of plantar flexor muscle activity relative to MTU length changes. This altered timing initiates a cascade of responses including increased MTU and fascicle length changes and increased muscle forces which, when taken together, enables the plantar flexors to effectively dissipate energy. Our results also show another mechanism, whereby increased co-activation of the plantar- and dorsiflexors enables shortening of the plantar flexor fascicles prior to ground contact. This co-activation improves the capacity of the plantar flexors to rapidly absorb energy upon ground contact, and may also aid in the avoidance of potentially damaging muscle strains. Our study provides novel insight into how humans alter their neural control to modulate in vivo muscle-tendon interaction dynamics in response to unexpected perturbations. These data provide essential insight to help guide design of lower-limb assistive devices that can perform within varied and unpredictable environments.


Asunto(s)
Músculo Esquelético , Tendones , Articulación del Tobillo , Fenómenos Biomecánicos , Elasticidad , Electromiografía , Humanos , Contracción Muscular
7.
J Exp Biol ; 224(12)2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-34096594

RESUMEN

The functional difference between the medial gastrocnemius (MG) and lateral gastrocnemius (LG) during walking in humans has not yet been fully established. Although evidence highlights that the MG is activated more than the LG, the link with potential differences in mechanical behavior between these muscles remains unknown. In this study, we aimed to determine whether differences in activation between the MG and LG translate into different fascicle behavior during walking. Fifteen participants walked at their preferred speed under two conditions: 0% and 10% incline treadmill grade. We used surface electromyography and B-mode ultrasound to estimate muscle activation and fascicle dynamics in the MG and LG. We observed a higher normalized activation in the MG than in the LG during stance, which did not translate into greater MG normalized fascicle shortening. However, we observed significantly less normalized fascicle lengthening in the MG than in the LG during early stance, which matched with the timing of differences in activation between muscles. This resulted in more isometric behavior of the MG, which likely influences the muscle-tendon interaction and enhances the catapult-like mechanism in the MG compared with the LG. Nevertheless, this interplay between muscle activation and fascicle behavior, evident at the group level, was not observed at the individual level, as revealed by the lack of correlation between the MG-LG differences in activation and MG-LG differences in fascicle behavior. The MG and LG are often considered as equivalent muscles but the neuromechanical differences between them suggest that they may have distinct functional roles during locomotion.


Asunto(s)
Músculo Esquelético , Caminata , Fenómenos Biomecánicos , Electromiografía , Humanos , Contracción Muscular , Tendones
8.
J Exp Biol ; 224(Pt 3)2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33376144

RESUMEN

Although cycling is a seemingly simple, reciprocal task, muscles must adapt their function to satisfy changes in mechanical demands induced by higher crank torques and faster pedalling cadences. We examined whether muscle function was sensitive to these changes in mechanical demands across a wide range of pedalling conditions. We collected experimental data of cycling where crank torque and pedalling cadence were independently varied from 13 to 44 N m and 60 to 140 rpm. These data were used in conjunction with musculoskeletal simulations and a recently developed functional index-based approach to characterise the role of human lower-limb muscles. We found that in muscles that generate most of the mechanical power and work during cycling, greater crank torque induced shifts towards greater muscle activation, greater positive muscle-tendon unit (MTU) work and a more motor-like function, particularly in the limb extensors. Conversely, with faster pedalling cadence, the same muscles exhibited a phase advance in muscle activity prior to crank top dead centre, which led to greater negative MTU power and work and shifted the muscles to contract with more spring-like behaviour. Our results illustrate the capacity for muscles to adapt their function to satisfy the mechanical demands of the task, even during highly constrained reciprocal tasks such as cycling. Understanding how muscles shift their contractile performance under varied mechanical and environmental demands may inform decisions on how to optimise pedalling performance and to design targeted cycling rehabilitation therapies for muscle-specific injuries or deficits.


Asunto(s)
Ciclismo , Contracción Muscular , Fenómenos Biomecánicos , Humanos , Extremidad Inferior , Músculo Esquelético , Músculos , Torque
9.
Biol Lett ; 17(2): 20200612, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33529545

RESUMEN

Geometric scaling predicts a major challenge for legged, terrestrial locomotion. Locomotor support requirements scale identically with body mass (α M1), while force-generation capacity should scale α M2/3 as it depends on muscle cross-sectional area. Mammals compensate with more upright limb postures at larger sizes, but it remains unknown how sprawling tetrapods deal with this challenge. Varanid lizards are an ideal group to address this question because they cover an enormous body size range while maintaining a similar bent-limb posture and body proportions. This study reports the scaling of ground reaction forces and duty factor for varanid lizards ranging from 7 g to 37 kg. Impulses (force×time) (α M0.99-1.34) and peak forces (α M0.73-1.00) scaled higher than expected. Duty factor scaled α M0.04 and was higher for the hindlimb than the forelimb. The proportion of vertical impulse to total impulse increased with body size, and impulses decreased while peak forces increased with speed.


Asunto(s)
Lagartos , Animales , Fenómenos Biomecánicos , Miembro Anterior , Miembro Posterior , Locomoción
10.
J Anat ; 237(6): 1114-1135, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32710503

RESUMEN

There is a functional trade-off in the design of skeletal muscle. Muscle strength depends on the number of muscle fibers in parallel, while shortening velocity and operational distance depend on fascicle length, leading to a trade-off between the maximum force a muscle can produce and its ability to change length and contract rapidly. This trade-off becomes even more pronounced as animals increase in size because muscle strength scales with area (length2 ) while body mass scales with volume (length3 ). In order to understand this muscle trade-off and how animals deal with the biomechanical consequences of size, we investigated muscle properties in the pectoral girdle of varanid lizards. Varanids are an ideal group to study the scaling of muscle properties because they retain similar body proportions and posture across five orders of magnitude in body mass and are highly active, terrestrially adapted reptiles. We measured muscle mass, physiological cross-sectional area, fascicle length, proximal and distal tendon lengths, and proximal and distal moment arms for 27 pectoral girdle muscles in 13 individuals across 8 species ranging from 64 g to 40 kg. Standard and phylogenetically informed reduced major axis regression was used to investigate how muscle architecture properties scale with body size. Allometric growth was widespread for muscle mass (scaling exponent >1), physiological cross-sectional area (scaling exponent >0.66), but not tendon length (scaling exponent >0.33). Positive allometry for muscle mass was universal among muscles responsible for translating the trunk forward and flexing the elbow, and nearly universal among humeral protractors and wrist flexors. Positive allometry for PCSA was also common among trunk translators and humeral protractors, though less so than muscle mass. Positive scaling for fascicle length was not widespread, but common among humeral protractors. A higher proportion of pectoral girdle muscles scaled with positive allometry than our previous work showed for the pelvic girdle, suggesting that the center of mass may move cranially with body size in varanids, or that the pectoral girdle may assume a more dominant role in locomotion in larger species. Scaling exponents for physiological cross-sectional area among muscles primarily associated with propulsion or with a dual role were generally higher than those associated primarily with support against gravity, suggesting that locomotor demands have at least an equal influence on muscle architecture as body support. Overall, these results suggest that larger varanids compensate for the increased biomechanical demands of locomotion and body support at higher body sizes by developing larger pectoral muscles with higher physiological cross-sectional areas. The isometric scaling rates for fascicle length among locomotion-oriented pectoral girdle muscles suggest that larger varanids may be forced to use shorter stride lengths, but this problem may be circumvented by increases in limb excursion afforded by the sliding coracosternal joint.


Asunto(s)
Lagartos/anatomía & histología , Locomoción/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/anatomía & histología , Animales , Fenómenos Biomecánicos/fisiología , Tamaño Corporal/fisiología , Marcha/fisiología , Lagartos/fisiología , Músculo Esquelético/fisiología
11.
PLoS Biol ; 15(1): e2000473, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28076354

RESUMEN

The survival of both the hunter and the hunted often comes down to speed. Yet how fast an animal can run is intricately linked to its size, such that the fastest animals are not the biggest nor the smallest. The ability to maintain high speeds is dependent on the body's capacity to withstand the high stresses involved with locomotion. Yet even when standing still, scaling principles would suggest that the mechanical stress an animal feels will increase in greater demand than its body can support. So if big animals want to be fast, they must find solutions to overcome these high stresses. This article explores the ways in which extant animals mitigate size-related increases in musculoskeletal stress in an effort to help understand where all the giants have gone.


Asunto(s)
Tamaño Corporal , Animales , Fenómenos Biomecánicos , Peso Corporal , Huesos/anatomía & histología , Mamíferos/anatomía & histología , Mamíferos/fisiología , Músculos/anatomía & histología , Postura/fisiología , Carrera/fisiología
12.
Nature ; 507(7490): 81-5, 2014 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-24598636

RESUMEN

Low-loss transmission and sensitive recovery of weak radio-frequency and microwave signals is a ubiquitous challenge, crucial in radio astronomy, medical imaging, navigation, and classical and quantum communication. Efficient up-conversion of radio-frequency signals to an optical carrier would enable their transmission through optical fibres instead of through copper wires, drastically reducing losses, and would give access to the set of established quantum optical techniques that are routinely used in quantum-limited signal detection. Research in cavity optomechanics has shown that nanomechanical oscillators can couple strongly to either microwave or optical fields. Here we demonstrate a room-temperature optoelectromechanical transducer with both these functionalities, following a recent proposal using a high-quality nanomembrane. A voltage bias of less than 10 V is sufficient to induce strong coupling between the voltage fluctuations in a radio-frequency resonance circuit and the membrane's displacement, which is simultaneously coupled to light reflected off its surface. The radio-frequency signals are detected as an optical phase shift with quantum-limited sensitivity. The corresponding half-wave voltage is in the microvolt range, orders of magnitude less than that of standard optical modulators. The noise of the transducer--beyond the measured 800 pV Hz-1/2 Johnson noise of the resonant circuit--consists of the quantum noise of light and thermal fluctuations of the membrane, dominating the noise floor in potential applications in radio astronomy and nuclear magnetic imaging. Each of these contributions is inferred to be 60 pV Hz-1/2 when balanced by choosing an electromechanical cooperativity of ~150 with an optical power of 1 mW. The noise temperature of the membrane is divided by the cooperativity. For the highest observed cooperativity of 6,800, this leads to a projected noise temperature of 40 mK and a sensitivity limit of 5 pV Hz-1/2. Our approach to all-optical, ultralow-noise detection of classical electronic signals sets the stage for coherent up-conversion of low-frequency quantum signals to the optical domain.

13.
J Exp Biol ; 222(Pt 6)2019 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-30814297

RESUMEN

Characterisation of an organism's performance in different habitats provides insight into the conditions that allow it to survive and reproduce. In recent years, the northern quoll (Dasyurus hallucatus) - a medium-sized semi-arboreal marsupial native to northern Australia - has undergone significant population declines within open forest, woodland and riparian habitats, but less so in rocky areas. To help understand this decline, we quantified the biomechanical performance of wild northern quolls as they ran up inclined narrow (13 mm pole) and inclined wide (90 mm platform) substrates. We predicted that quolls may possess biomechanical adaptations to increase stability on narrow surfaces, which are more common in rocky habitats. Our results showed that quolls have some biomechanical characteristics consistent with a stability advantage on narrow surfaces. This includes the coupled use of limb pairs, as indicated via a decrease in footfall time, and an ability to produce corrective torques to counteract the toppling moments commonly encountered during gait on narrow surfaces. However, speed was constrained on narrow surfaces, and quolls did not adopt diagonal sequence gaits, unlike true arboreal specialists such as primates. In comparison with key predators, such as cats and dogs, northern quolls appear inferior in terrestrial environments but have a stability advantage at higher speeds on narrow supports. This may partially explain the heterogeneous declines in northern quoll populations among various habitats on mainland Australia.


Asunto(s)
Locomoción , Marsupiales/fisiología , Animales , Fenómenos Biomecánicos , Ambiente , Femenino , Masculino , Northern Territory
14.
J Neuroeng Rehabil ; 16(1): 57, 2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-31092269

RESUMEN

BACKGROUND: Ankle exoskeletons offer a promising opportunity to offset mechanical deficits after stroke by applying the needed torque at the paretic ankle. Because joint torque is related to gait speed, it is important to consider the user's gait speed when determining the magnitude of assistive joint torque. We developed and tested a novel exoskeleton controller for delivering propulsive assistance which modulates exoskeleton torque magnitude based on both soleus muscle activity and walking speed. The purpose of this research is to assess the impact of the resulting exoskeleton assistance on post-stroke walking performance across a range of walking speeds. METHODS: Six participants with stroke walked with and without assistance applied to a powered ankle exoskeleton on the paretic limb. Walking speed started at 60% of their comfortable overground speed and was increased each minute (n00, n01, n02, etc.). We measured lower limb joint and limb powers, metabolic cost of transport, paretic and non-paretic limb propulsion, and trailing limb angle. RESULTS: Exoskeleton assistance increased with walking speed, verifying the speed-adaptive nature of the controller. Both paretic ankle joint power and total limb power increased significantly with exoskeleton assistance at six walking speeds (n00, n01, n02, n03, n04, n05). Despite these joint- and limb-level benefits associated with exoskeleton assistance, no subject averaged metabolic benefits were evident when compared to the unassisted condition. Both paretic trailing limb angle and integrated anterior paretic ground reaction forces were reduced with assistance applied as compared to no assistance at four speeds (n00, n01, n02, n03). CONCLUSIONS: Our results suggest that despite appropriate scaling of ankle assistance by the exoskeleton controller, suboptimal limb posture limited the conversion of exoskeleton assistance into forward propulsion. Future studies could include biofeedback or verbal cues to guide users into limb configurations that encourage the conversion of mechanical power at the ankle to forward propulsion. TRIAL REGISTRATION: N/A.


Asunto(s)
Articulación del Tobillo/fisiología , Dispositivo Exoesqueleto , Rehabilitación de Accidente Cerebrovascular/instrumentación , Velocidad al Caminar/fisiología , Caminata/fisiología , Adulto , Fenómenos Biomecánicos/fisiología , Electromiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Nature ; 490(7420): 380-3, 2012 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-23075988

RESUMEN

Electron spins trapped in quantum dots have been proposed as basic building blocks of a future quantum processor. Although fast, 180-picosecond, two-quantum-bit (two-qubit) operations can be realized using nearest-neighbour exchange coupling, a scalable, spin-based quantum computing architecture will almost certainly require long-range qubit interactions. Circuit quantum electrodynamics (cQED) allows spatially separated superconducting qubits to interact via a superconducting microwave cavity that acts as a 'quantum bus', making possible two-qubit entanglement and the implementation of simple quantum algorithms. Here we combine the cQED architecture with spin qubits by coupling an indium arsenide nanowire double quantum dot to a superconducting cavity. The architecture allows us to achieve a charge-cavity coupling rate of about 30 megahertz, consistent with coupling rates obtained in gallium arsenide quantum dots. Furthermore, the strong spin-orbit interaction of indium arsenide allows us to drive spin rotations electrically with a local gate electrode, and the charge-cavity interaction provides a measurement of the resulting spin dynamics. Our results demonstrate how the cQED architecture can be used as a sensitive probe of single-spin physics and that a spin-cavity coupling rate of about one megahertz is feasible, presenting the possibility of long-range spin coupling via superconducting microwave cavities.

16.
Ann Oncol ; 28(7): 1427-1435, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28200082

RESUMEN

BACKGROUND: Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. METHODS: We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. RESULTS: Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. CONCLUSION: A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping.


Asunto(s)
Antineoplásicos/administración & dosificación , Ensayos Clínicos Fase I como Asunto/estadística & datos numéricos , Oncología Médica/estadística & datos numéricos , Neoplasias/tratamiento farmacológico , Proyectos de Investigación/estadística & datos numéricos , Antineoplásicos/efectos adversos , Simulación por Computador , Interpretación Estadística de Datos , Relación Dosis-Respuesta a Droga , Cálculo de Dosificación de Drogas , Determinación de Punto Final/estadística & datos numéricos , Humanos , Dosis Máxima Tolerada , Modelos Estadísticos , Neoplasias/diagnóstico , Tamaño de la Muestra , Factores de Tiempo , Resultado del Tratamiento
17.
Phys Rev Lett ; 119(9): 097702, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28949587

RESUMEN

We demonstrate a single atom maser consisting of a semiconductor double quantum dot (DQD) that is embedded in a high-quality-factor microwave cavity. A finite bias drives the DQD out of equilibrium, resulting in sequential single electron tunneling and masing. We develop a dynamic tuning protocol that allows us to controllably increase the time-averaged repumping rate of the DQD at a fixed level detuning, and quantitatively study the transition through the masing threshold. We further examine the crossover from incoherent to coherent emission by measuring the photon statistics across the masing transition. The observed threshold behavior is in agreement with an existing single atom maser theory when small corrections from lead emission are taken into account.

18.
Phys Rev Lett ; 119(23): 233601, 2017 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-29286689

RESUMEN

We demonstrate the emergence of universal Efimov physics for interacting photons in cold gases of Rydberg atoms. We consider the behavior of three photons injected into the gas in their propagating frame, where a paraxial approximation allows us to consider them as massive particles. In contrast to atoms and nuclei, the photons have a large anisotropy between their longitudinal mass, arising from dispersion, and their transverse mass, arising from diffraction. Nevertheless, we show that, in suitably rescaled coordinates, the effective interactions become dominated by s-wave scattering near threshold and, as a result, give rise to an Efimov effect near unitarity. We show that the three-body loss of these Efimov trimers can be strongly suppressed and determine conditions under which these states are observable in current experiments. These effects can be naturally extended to probe few-body universality beyond three bodies, as well as the role of Efimov physics in the nonequilibrium, many-body regime.

19.
J Exp Biol ; 220(Pt 9): 1643-1653, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28202584

RESUMEN

Hill-type models are ubiquitous in the field of biomechanics, providing estimates of a muscle's force as a function of its activation state and its assumed force-length and force-velocity properties. However, despite their routine use, the accuracy with which Hill-type models predict the forces generated by muscles during submaximal, dynamic tasks remains largely unknown. This study compared human gastrocnemius forces predicted by Hill-type models with the forces estimated from ultrasound-based measures of tendon length changes and stiffness during cycling, over a range of loads and cadences. We tested both a traditional model, with one contractile element, and a differential model, with two contractile elements that accounted for independent contributions of slow and fast muscle fibres. Both models were driven by subject-specific, ultrasound-based measures of fascicle lengths, velocities and pennation angles and by activation patterns of slow and fast muscle fibres derived from surface electromyographic recordings. The models predicted, on average, 54% of the time-varying gastrocnemius forces estimated from the ultrasound-based methods. However, differences between predicted and estimated forces were smaller under low speed-high activation conditions, with models able to predict nearly 80% of the gastrocnemius force over a complete pedal cycle. Additionally, the predictions from the Hill-type muscle models tested here showed that a similar pattern of force production could be achieved for most conditions with and without accounting for the independent contributions of different muscle fibre types.


Asunto(s)
Modelos Biológicos , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Adulto , Ciclismo/fisiología , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Ultrasonografía
20.
Phys Rev Lett ; 117(5): 056801, 2016 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-27517784

RESUMEN

We investigate the nonclassical states of light that emerge in a microwave resonator coupled to a periodically driven electron in a nanowire double quantum dot (DQD). Under certain drive configurations, we find that the resonator approaches a thermal state at the temperature of the surrounding substrate with a chemical potential given by a harmonic of the drive frequency. Away from these thermal regions we find regions of gain and loss, where the system can lase, or regions where the DQD acts as a single-photon source. These effects are observable in current devices and have broad utility for quantum optics with microwave photons.

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