Approaching the motional ground state of a 10-kg object.

The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object's motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales. We prepared the center-of-mass motion of a 10-kilogram mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in temperature, from room temperature to 77 nanokelvin, is commensurate with an 11 orders-of-magnitude suppression of quantum back-action by feedback and a 13 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state. Our approach will enable the possibility of probing gravity on massive quantum systems.

Outcome of one-stage correction of deformities of the ankle and hindfoot and fusion in Charcot neuroarthropathy using a retrograde intramedullary hindfoot arthrodesis nail.

We report the outcomes of 20 patients (12 men, 8 women, 21 feet) with Charcot neuro-arthropathy who underwent correction of deformities of the ankle and hindfoot using retrograde intramedullary nail arthrodesis. The mean age of the patients was 62.6 years (46 to 83); their mean BMI was 32.7 (15 to 47) and their median American Society of Anaesthetists score was 3 (2 to 4). All presented with severe deformities and 15 had chronic ulceration. All were treated with reconstructive surgery and seven underwent simultaneous midfoot fusion using a bolt, locking plate or a combination of both. At a mean follow-up of 26 months (8 to 54), limb salvage was achieved in all patients and 12 patients (80%) with ulceration achieved healing and all but one patient regained independent mobilisation. There was failure of fixation with a broken nail requiring revision surgery in one patient. Migration of distal locking screws occurred only when standard screws had been used but not with hydroxyapatite-coated screws. The mean American Academy of Orthopaedic Surgeons Foot and Ankle (AAOS-FAO) score improved from 50.7 (17 to 88) to 65.2 (22 to 88), (p = 0.015). The mean Short Form (SF)-36 Health Survey Physical Component Score improved from 25.2 (16.4 to 42.8) to 29.8 (17.7 to 44.2), (p = 0.003) and the mean Euroqol EQ­5D­5L score improved from 0.63 (0.51 to 0.78) to 0.67 (0.57 to 0.84), (p = 0.012). Single-stage correction of deformity using an intramedullary hindfoot arthrodesis nail is a good form of treatment for patients with severe Charcot hindfoot deformity, ulceration and instability provided a multidisciplinary care plan is delivered.

Comparative metabolism of 2,4-dichlorophenoxyacetic acid (2,4-D) in rat and dog.

1. There is a significant species difference in the toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D). The oral no overall adverse effect level (NOAEL) for chronic toxicity of 2,4-D in rat is 5 mg kg(-1) day(-1) and in dog is 1 mg kg(-1) day(-1). The maximum tolerated dose (MTD) in rat is 150 and 75 kg(-1) day(-1) for male and females, respectively. The MTD in dog is 7.5 mg kg(-1) day(-1) for males and females. 2. In an attempt to explain the increased sensitivity to 2,4-D in dog, male and female rats and dogs were orally dosed with either 5 or 50 mg kg(-1) 14C-2,4-D. The rates and routes of excretion were investigated along with plasma toxicokinetics and biotransformation of the compound. 3. Elimination of the radioactive dose of 2,4-D from rat plasma was significantly faster than in dog. The approximate t(1/2) were 1.3-3.4 h for rat and 99-134 h for dog following a 5 or 50 mg kg(-1) dose, respectively. This led to large differences in the calculated AUC(0-infinity) 21-57 microg eq. h g(-1) for rat and 4889-5298 microg eq. h g(-1) for dog at 5 mg kg(-1), and 122-2358 microg eq. h g(-1) for rat and 34,110-44,296 microg eq. h g(-1) for dog at 50 mg kg(-1)). 4. In rat, the major route of excretion was in the urine. Excretion was essentially complete after 24 h for the low dose and after 48 h for the high dose. For dog, elimination was incomplete over the sampling period with only about 50% of the dose recovered. Urine was the principal route of excretion at the low dose, but about equal amounts were excreted in urine and faeces at the high dose over 120 h. 5. In rat, 2,4-D was unmetabolized and excreted in urine as the parent compound. In dog, the dose was excreted mainly following metabolism. 2,4-D in dog was conjugated forming the taurine, serine, glycine, glutamic acid, cysteine, sulphate and glucuronide conjugates, plus an unidentified metabolite, which were excreted in urine. Plasma, however, only contained unmetabolized 2,4-D. 6. The results show that the body burden of 2,4-D in dog is significantly higher than in rat for an equivalent dose, which is consistent with the increased sensitivity of dog to 2,4-D toxicity.

Absorption, metabolism and excretion of 4-chloro-2-methylphenoxyacetic acid (MCPA) in rat and dog.

1. The oral no overall adverse effect level (NOAEL) for chronic toxicity of 4-chloro-2-methylphenoxyacetic acid (MCPA) in rat is approximately 1.3 mg kg(-1) and in dog is 0.2 mg kg(-1). In an attempt to explain the difference in toxicology between these species, rats and dogs were orally dosed with (14C)-MCPA at 5 or 100 mgkg(-1) and plasma toxicokinetics, rates and routes of excretion and biotransformation were investigated. 2. Elimination of radioactivity in rat plasma was biphasic and in dog was monophasic. Rat eliminated radioactivity from plasma significantly faster than dog (approximate values biased on total radioactivity: 5 mg kg(-1) rat: t 1/2 dist 3.5 h, t 1/2 elim 17.2-36.2 h, AUC(0-infinity) 230 microg equiv hg(-1); 5 mg kg(-1) dog: t 1/2 47h, AUC(0-infinity) 2,500 microg equiv h g(-1); 100 mg kg(-1) rat: t 1/2 dist 10h, t 1/2 elim 10.27-25.4h, AUC(0-infinity) 5,400 microg equiv hg(-1); l00 mg kg(-1) dog: t 1/2 h, AUC(0-infinity) 20,500 microg eqiv h g(-1). 3. For both species, the principal route of excretion was in urine but renal elimination was notably more rapid and more extensive in rat. 4. In both rat and dog, excretion of radioactivity was mainly as MCPA and its hydroxylated metabolite hydroxymethylphenoxyacetic acid (HMCPA). In rat, both were mainly excreted as the free acids although a small proportion was conjugated. In dog, the proportion of HMCPA was increased and the majority of both species was excreted as glycine or taurine conjugates. 5. These data, along with previously published accounts, indicate that renal elimination of MCPA in dog is substantially slower than in rat resulting in disproportionate elevation of AUC (based on total radioactivity) in dog compared with rat.

Longitudinal study of urinary hydroxy-pyridinium cross-links and growth in healthy infants: higher values with breastfeeding and after daytime sleep.

Urinary pyridinoline and deoxypyridinoline crosslinks (crosslink) are excreted when bone is resorbed. The aims of this study in healthy infants were to determine whether crosslinks a) could predict growth velocity, b) are variable due to circadian rhythm, and c) differ in infants who were either breast-fed or formula-fed. In 78 healthy infants (48 male; 30 female) urine samples were collected and anthropometric measurements were taken at 2, 3, 4, 5, 6, 8, 10 and 12 months of age. In addition, a total of 25 samples were collected during the day (0700-2000) in 5 of the infants to determine circadian rhythm of crosslink excretion. Crosslink excretion decreased (p < 0.001) with age between 2 and 12 months. Pyridinoline excretion showed a significant, but weak correlation (r > or = 0.21; p < 0.05) with linear growth velocity and weight velocity in the subsequent month until 6 months of age, and no correlation thereafter. Infants studied for circadian rhythm showed a 63% greater (p < 0.05) rate of pyridinoline excretion after a nap as compared to the 13-hour mean value. In a subset of infants whose energy intake was exclusively from breast milk (BF, n = 23) or formula (FF, n = 10), crosslink excretion was greater in BF infants at 3 months of age (p < 0.05). The correlations between crosslink excretion and growth parameters indicate that crosslinks may be useful as a marker of growth in infant populations. However sources of variation in crosslink excretion, such as circadian rhythm and diet may limit their utility to predict growth in an individual infant. These factors should be considered in future studies examining markers of bone turnover in infants.