Higher risk of opioid-induced respiratory depression in children with neurodevelopmental disability: a retrospective cohort study of 12,904 patients

BACKGROUND: Children with neurodevelopmental disabilities may be at risk of opioid-induced respiratory depression. We aimed to quantify the risks and effectiveness of morphine nurse-controlled analgesia (morphine-NCA) for postoperative pain in children with neurodevelopmental disabilities. METHODS: We carried out a retrospective cohort study of 12 904 children who received postoperative i.v. morphine-NCA. Subjects were divided into a neurodevelopmental disability group and a control group. Rates of clinical satisfaction, respiratory depression, and serious adverse events were obtained, and statistical analysis, including multilevel logistic regression using Bayesian inference, was performed. RESULTS: Of 12 904 patients, 2390 (19%) had neurodevelopmental disabilities. There were 88 instances of respiratory depression and 52 serious adverse events; there were no opioid-related deaths. The cumulative incidence of respiratory depression in the neurodevelopmental disability group was 1.09% vs 0.59% in the control group [odds ratio 1.8 (98% chance that the true odds ratio was >1)]. A significant interaction between postoperative morphine dose and neurodevelopmental disabilities was observed, with higher risk of respiratory depression with increasing dose. Satisfaction with morphine-NCA was very high overall, although children with neurodevelopmental disabilities were 1% more likely to have infusions rated as fair or poor (3.3 vs 2.1%, χ2P<0.001). CONCLUSIONS: Children with neurodevelopmental disabilities were 1.8 times more likely to suffer respiratory depression, absolute risk difference 0.5%; opioid-induced respiratory depression in this group may relate to increased sensitivity to dose-relate respiratory effects of morphine. Morphine-NCA as described was an acceptable technique for children with and without neurodevelopmental disabilities

Sequestration of Martian CO2 by mineral carbonation

Carbonation is the water-mediated replacement of silicate minerals, such as olivine, by carbonate, and is commonplace in the Earth’s crust. This reaction can remove significant quantities of CO2 from the atmosphere and store it over geological timescales. Here we present the first direct evidence for CO2 sequestration and storage on Mars by mineral carbonation. Electron beam imaging and analysis show that olivine and a plagioclase feldspar-rich mesostasis in the Lafayette meteorite have been replaced by carbonate. The susceptibility of olivine to replacement was enhanced by the presence of smectite veins along which CO2-rich fluids gained access to grain interiors. Lafayette was partially carbonated during the Amazonian, when liquid water was available intermittently and atmospheric CO2 concentrations were close to their present-day values. Earlier in Mars’ history, when the planet had a much thicker atmosphere and an active hydrosphere, carbonation is likely to have been an effective mechanism for sequestration of CO2

A Sox2–Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells

Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer

A Randomised Trial to Compare the Safety, Tolerability and Efficacy of Three Drug Combinations for Intermittent Preventive Treatment in Children

BACKGROUND: Results from trials of intermittent preventive treatment (IPT) in infants and children have shown that IPT provides significant protection against clinical malaria. Sulfadoxine-pyrimethamine (SP) given alone or in combination with other drugs has been used for most IPT programmes. However, SP resistance is increasing in many parts of Africa. Thus, we have investigated whether SP plus AQ, SP plus piperaquine (PQ) and dihydroartemisinin (DHA) plus PQ might be equally safe and effective when used for IPT in children in an area of seasonal transmission. METHODS: During the 2007 malaria transmission season, 1008 Gambian children were individually randomized to receive SP plus amodiaquine (AQ), SP plus piperaquine (PQ) or dihydroartemisinin (DHA) plus PQ at monthly intervals on three occasions during the peak malaria transmission season. To determine the risk of side effects following drug administration, participants in each treatment group were visited at home three days after the start of each round of drug administration and a side effects questionnaire completed. To help establish whether adverse events were drug related, the same questionnaire was administered to 286 age matched control children recruited from adjacent villages. Morbidity was monitored throughout the malaria transmission season and study children were seen at the end of the malaria transmission season. RESULTS: All three treatment regimens showed good safety profiles. No severe adverse event related to IPT was reported. The most frequent adverse events reported were coughing, diarrhoea, vomiting, abdominal pain and loss of appetite. Cough was present in 15.2%, 15.4% and 18.7% of study subjects who received SP plus AQ, DHA plus PQ or SP plus PQ respectively, compared to 19.2% in a control group. The incidence of malaria in the DHA plus PQ, SP plus AQ and SP plus PQ groups were 0.10 cases per child year (95% CI: 0.05, 0.22), 0.06 (95% CI: 0.022, 0.16) and 0.06 (95% CI: 0.02, 0.15) respectively. The incidence of malaria in the control group was 0.79 cases per child year (0.58, 1.08). CONCLUSION: All the three regimens of IPT in children were safe and highly efficacious TRIAL REGISTRATION: ClinicalTrials.gov NCT00561899

Turbulent ‘stopping plumes’ and plume pinch-off in uniform surroundings

Observations of turbulent convection in the environment are of variously sus- tained plume-like flows or intermittent thermal-like flows. At different times of the day the prevailing conditions may change and consequently the observed flow regimes may change. Understanding the link between these flows is of practical importance meteorologically, and here we focus our interest upon plume-like regimes that break up to form thermal-like regimes. It has been shown that when a plume rises from a boundary with low conductivity, such as arable land, the inability to maintain a rapid enough supply of buoyancy to the plume source can result in the turbulent base of the plume separating and rising away from the source. This plume ‘pinch-off’ marks the onset of the intermittent thermal-like behavior. The dynamics of turbulent plumes in a uniform environment are explored in order to investigate the phenomenon of plume pinch-off. The special case of a turbulent plume having its source completely removed, a ‘stopping plume’, is considered in particular. The effects of forcing a plume to pinch-off, by rapidly reducing the source buoyancy flux to zero, are shown experi- mentally. We release saline solution into a tank filled with fresh water generating downward propagating steady turbulent plumes. By rapidly closing the plume nozzle, the plumes are forced to pinch-off. The plumes are then observed to detach from the source and descend into the ambient. The unsteady buoyant region produced after pinch-off, cannot be described by the power-law behavior of either classical plumes or thermals, and so the terminology ‘stopping plume’ (analogous to a ‘starting plume’) is adopted for this type of flow. The propagation of the stopping plume is shown to be approximately linearly dependent on time, and we speculate therefore that the closure of the nozzle introduces some vorticity into the ambient, that may roll up to form a vortex ring dominating the dynamics of the base of a stopping plume

Fabrication of super-hydrophobic nickel film on copper substrate with improved corrosion inhibition by electrodeposition process

Inspired by the famous “lotus effect”, we have fabricated the super-hydrophobic surfaces with nickel film on copper substrates using a one-step electrodeposition method. By adjusting processing time, water contact angle of as-prepared surfaces can reach as high as 160.3 ± 1.5° with small rolling angle of 3.0 ± 0.5°, showing excellent super-hydrophobicity. After the deposition of nickel coating, the pristine copper surfaces became much rough with packed cauliflower-/thorn-like clusters. This unique surface texture contributed to trapping large amount of air and forming the air cushion underneath the water droplet, which can prevent the liquids contacting the copper substrate. The examination of surface chemical compositions implied that the deposited super-hydrophobic coating consisted of nickel crystals and nickel myristate. In this research, the formation mechanism of the electrodeposited super-hydrophobicity was extensively explained based on the analyses of surface texture and surface chemistry. Moreover, the corrosion resistance of the as-fabricated super-hydrophobic surface was estimated by the potentiodynamic polarization tests as well as the electrochemical impedance spectroscopy (EIS) measurements. The results demonstrate that the super-hydrophobic nickel coating showed excellent corrosion inhibition in simulated seawater solution. The existence of the super-hydrophobic coating could be regarded as a barrier and thus provide a perfect air-liquid interface that inhibits the penetration of the corrosive ions. This facile and effective method of electrodeposition process offers a promising approach for mass production of super-hydrophobic surfaces on various metals

Effect of predictive sign of acceleration on heart rate variability in passive translation situation: preliminary evidence using visual and vestibular stimuli in VR environment

<p>Abstract</p> <p>Objective</p> <p>We studied the effects of the presentation of a visual sign that warned subjects of acceleration around the yaw and pitch axes in virtual reality (VR) on their heart rate variability.</p> <p>Methods</p> <p>Synchronization of the immersive virtual reality equipment (CAVE) and motion base system generated a driving scene and provided subjects with dynamic and wide-ranging depth information and vestibular input. The heart rate variability of 21 subjects was measured while the subjects observed a simulated driving scene for 16 minutes under three different conditions.</p> <p>Results</p> <p>When the predictive sign of the acceleration appeared 3500 ms before the acceleration, the index of the activity of the autonomic nervous system (low/high frequency ratio; LF/HF ratio) of subjects did not change much, whereas when no sign appeared the LF/HF ratio increased over the observation time. When the predictive sign of the acceleration appeared 750 ms before the acceleration, no systematic change occurred.</p> <p>Conclusion</p> <p>The visual sign which informed subjects of the acceleration affected the activity of the autonomic nervous system when it appeared long enough before the acceleration. Also, our results showed the importance of the interval between the sign and the event and the relationship between the gradual representation of events and their quantity.</p