Detection of pediatric upper extremity motor activity and deficits with accelerometry

Importance: Affordable, quantitative methods to screen children for developmental delays are needed. Motor milestones can be an indicator of developmental delay and may be used to track developmental progress. Accelerometry offers a way to gather real-world information about pediatric motor behavior. Objective: To develop a referent cohort of pediatric accelerometry from bilateral upper extremities (UEs) and determine whether movement can accurately distinguish those with and without motor deficits. Design, Setting, and Participants: Children aged 0 to 17 years participated in a prospective cohort from December 8, 2014, to December 29, 2017. Children were recruited from Ranken Jordan Pediatric Bridge Hospital, Maryland Heights, Missouri, and Washington University School of Medicine in St Louis, St Louis, Missouri. Typically developing children were included as a referent cohort if they had no history of motor or neurological deficit; consecutive sampling and matching ensured equal representation of sex and age. Children with diagnosed asymmetric motor deficits were included in the motor impaired cohort. Exposures: Bilateral UE motor activity was measured using wrist-worn accelerometers for a total of 100 hours in 25-hour increments. Main Outcomes and Measures: To characterize bilateral UE motor activity in a referent cohort for the purpose of detecting irregularities in the future, total activity and the use ratio between UEs were used to describe typically developing children. Asymmetric impairment was classified using the mono-arm use index (MAUI) and bilateral-arm use index (BAUI) to quantify the acceleration of unilateral movements. Results: A total of 216 children enrolled, and 185 children were included in analysis. Of these, 156 were typically developing, with mean (SD) age 9.1 (5.1) years and 81 boys (52.0%). There were 29 children in the motor impaired cohort, with mean (SD) age 7.4 (4.4) years and 16 boys (55.2%). The combined MAUI and BAUI (mean [SD], 0.86 [0.005] and use ratio (mean [SD], 0.90 [0.008]) had similar F1 values. The area under the curve was also similar between the combined MAUI and BAUI (mean [SD], 0.98 [0.004]) and the use ratio (mean [SD], 0.98 [0.004]). Conclusions and Relevance: Bilateral UE movement as measured with accelerometry may provide a meaningful metric of real-world motor behavior across childhood. Screening in early childhood remains a challenge; MAUI may provide an effective method for clinicians to measure and visualize real-world motor behavior in children at risk for asymmetrical deficits

The Carnegie-Chicago Hubble Program. VIII. An Independent Determination of the Hubble Constant Based on the Tip of the Red Giant Branch

We present a new and independent determination of the local value of the Hubble constant based on a calibration of the Tip of the Red Giant Branch (TRGB) applied to Type Ia supernovae (SNeIa). We find a value of Ho = 69.8 +/- 0.8 (+/-1.1\% stat) +/- 1.7 (+/-2.4\% sys) km/sec/Mpc. The TRGB method is both precise and accurate, and is parallel to, but independent of the Cepheid distance scale. Our value sits midway in the range defined by the current Hubble tension. It agrees at the 1.2-sigma level with that of the Planck 2018 estimate, and at the 1.7-sigma level with the SHoES measurement of Ho based on the Cepheid distance scale. The TRGB distances have been measured using deep Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) imaging of galaxy halos. The zero point of the TRGB calibration is set with a distance modulus to the Large Magellanic Cloud of 18.477 +/- 0.004 (stat) +/-0.020 (sys) mag, based on measurement of 20 late-type detached eclipsing binary (DEB) stars, combined with an HST parallax calibration of a 3.6 micron Cepheid Leavitt law based on Spitzer observations. We anchor the TRGB distances to galaxies that extend our measurement into the Hubble flow using the recently completed Carnegie Supernova Project I sample containing about 100 well-observed SNeIa. There are several advantages of halo TRGB distance measurements relative to Cepheid variables: these include low halo reddening, minimal effects of crowding or blending of the photometry, only a shallow (calibrated) sensitivity to metallicity in the I-band, and no need for multiple epochs of observations or concerns of different slopes with period. In addition, the host masses of our TRGB host-galaxy sample are higher on average than the Cepheid sample, better matching the range of host-galaxy masses in the CSP distant sample, and reducing potential systematic effects in the SNeIa measurements.Comment: 60 pages, 20 figures, accepted for publication in the Astrophysical Journa

Appetite Suppression and Altered Food Preferences Coincide with Changes in Appetite-Mediating Hormones During Energy Deficit at High Altitude, But Are Not Affected by Protein Intake

Appetite suppression and altered food preferences coincide with changes in appetite-mediating hormones during energy deficit at high altitude, but are not affected by protein intake. High Alt Med Biol. 19:156–169, 2018.—Anorexia and unintentional body weight loss are common during high altitude (HA) sojourn, but underlying mechanisms are not fully characterized, and the impact of dietary macronutrient composition on appetite regulation at HA is unknown. This study aimed to determine the effects of a hypocaloric higher protein diet on perceived appetite and food preferences during HA sojourn and to examine longitudinal changes in perceived appetite, appetite mediating hormones, and food preferences during acclimatization and weight loss at HA. Following a 21-day level (SL) period, 17 unacclimatized males ascended to and resided at HA (4300 m) for 22 days. At HA, participants were randomized to consume measured standard-protein (1.0 g protein/kg/d) or higher protein (2.0 g/kg/d) hypocaloric diets (45% carbohydrate, 30% energy restriction) and engaged in prescribed physical activity to induce an estimated 40% energy deficit. Appetite, food preferences, and appetite-mediating hormones were measured at SL and at the beginning and end of HA. Diet composition had no effect on any outcome. Relative to SL, appetite was lower during acute HA (days 0 and 1), but not different after acclimatization and weight loss (HA day 18), and food preferences indicated an increased preference for sweet- and low-protein foods during acute HA, but for high-fat foods after acclimatization and weight loss. Insulin, leptin, and cholecystokinin concentrations were elevated during acute HA, but not after acclimatization and weight loss, whereas acylated ghrelin concentrations were suppressed throughout HA. Findings suggest that appetite suppression and altered food preferences coincide with changes in appetite-mediating hormones during energy deficit at HA. Although dietary protein intake did not impact appetite, the possible incongruence with food preferences at HA warrants consideration when developing nutritional strategies for HA sojourn

Quantum Computing and Quantum Simulation with Group-II Atoms

Recent experimental progress in controlling neutral group-II atoms for optical clocks, and in the production of degenerate gases with group-II atoms has given rise to novel opportunities to address challenges in quantum computing and quantum simulation. In these systems, it is possible to encode qubits in nuclear spin states, which are decoupled from the electronic state in the $^1$S$_0$ ground state and the long-lived $^3$P$_0$ metastable state on the clock transition. This leads to quantum computing scenarios where qubits are stored in long lived nuclear spin states, while electronic states can be accessed independently, for cooling of the atoms, as well as manipulation and readout of the qubits. The high nuclear spin in some fermionic isotopes also offers opportunities for the encoding of multiple qubits on a single atom, as well as providing an opportunity for studying many-body physics in systems with a high spin symmetry. Here we review recent experimental and theoretical progress in these areas, and summarise the advantages and challenges for quantum computing and quantum simulation with group-II atoms.Comment: 11 pages, 7 figures, review for special issue of "Quantum Information Processing" on "Quantum Information with Neutral Particles

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20–50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time