Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

Imaging the lithosphere beneath NE Tibet: Teleseismic P and S body wave tomography incorporating surface wave starting models

The northeastern margin of the Tibetan Plateau, which includes the Qiangtang and Songpan-Ganzi terranes as well as the Kunlun Shan and the Qaidam Basin, continues to deform in response to the ongoing India–Eurasia collision. To test competing hypotheses concerning the mechanisms for this deformation, we assembled a high-quality data set of approximately 14 000 P- and 4000 S-wave arrival times from earthquakes at teleseismic distances from the International Deep Profiling of Tibet and the Himalaya, Phase IV broad-band seismometer deployments. We analyse these arrival times to determine tomographic images of P- and S-wave velocities in the upper mantle beneath this part of the plateau. To account for the effects of major heterogeneity in crustal and uppermost mantle wave velocities in Tibet, we use recent surface wave models to construct a starting model for our teleseismic body wave inversion. We compare the results from our model with those from simpler starting models, and find that while the reduction in residuals and results for deep structure are similar between models, the results for shallow structure are different. Checkerboard tests indicate that features of ~125km length scale are reliably imaged throughout the study region. Using synthetic tests, we show that the best recovery is below ~300km, and that broad variations in shallow structure can also be recovered. We also find that significant smearing can occur, especially at the edges of the model. We observe a shallow dipping seismically fast structure at depths of ~140–240km, which dies out gradually between 33°N and 35°N. Based on the lateral continuity of this structure (from the surface waves) we interpret it as Indian lithosphere. Alternatively, the entire area could be thickened by pure shear, or the northern part could be an underthrust Lhasa Terrane lithospheric slab with only the southern part from India. We see a deep fast wave velocity anomaly (below 300?km), that is consistent with receiver function observations of a thickened transition zone and could be a fragment of oceanic lithosphere. In NE Tibet, it appears to be disconnected from faster wave velocities above (i.e. it is not downwelling or subducting here). Our models corroborate results of previous work which imaged a relatively slow wave velocity region below the Kunlun Shan and northern Songpan-Ganzi Terrane, which is difficult to reconcile with the hypothesis of southward-directed continental subduction at the northern margin. Wave velocities in the shallow mantle beneath the Qaidam Basin are faster than normal, and more so in the east than the west.This work was supported by a Natural Environment Research Council studentship (grant NE/H52449X/1)This version of record of this article can be found in Geophysical Journal International (March, 2014) 196 (3): 1724-1741. doi: 10.1093/gji/ggt47

Cough quality in children: a comparison of subjective vs. bronchoscopic findings

BACKGROUND: Cough is the most common symptom presenting to doctors. The quality of cough (productive or wet vs dry) is used clinically as well as in epidemiology and clinical research. There is however no data on the validity of cough quality descriptors. The study aims were to compare (1) cough quality (wet/dry and brassy/non-brassy) to bronchoscopic findings of secretions and tracheomalacia respectively and, (2) parent's vs clinician's evaluation of the cough quality (wet/dry). METHODS: Cough quality of children (without a known underlying respiratory disease) undergoing elective bronchoscopy was independently evaluated by clinicians and parents. A 'blinded' clinician scored the secretions seen at bronchoscopy on pre-determined criteria and graded (1 to 6). Kappa (K) statistics was used for agreement, and inter-rater and intra-rater agreement examined on digitally recorded cough. A receiver operating characteristic (ROC) curve was used to determine if cough quality related to amount of airway secretions present at bronchoscopy. RESULTS: Median age of the 106 children (62 boys, 44 girls) enrolled was 2.6 years (IQR 5.7). Parent's assessment of cough quality (wet/dry) agreed with clinicians' (K = 0.75, 95%CI 0.58–0.93). When compared to bronchoscopy (bronchoscopic secretion grade 4), clinicians' cough assessment had the highest sensitivity (0.75) and specificity (0.79) and were marginally better than parent(s). The area under the ROC curve was 0.85 (95%CI 0.77–0.92). Intra-observer (K = 1.0) and inter-clinician agreement for wet/dry cough (K = 0.88, 95%CI 0.82–0.94) was very good. Weighted K for inter-rater agreement for bronchoscopic secretion grades was 0.95 (95%CI 0.87–1). Sensitivity and specificity for brassy cough (for tracheomalacia) were 0.57 and 0.81 respectively. K for both intra and inter-observer clinician agreement for brassy cough was 0.79 (95%CI 0.73–0.86). CONCLUSIONS: Dry and wet cough in children, as determined by clinicians and parents has good clinical validity. Clinicians should however be cognisant that children with dry cough may have minimal to mild airway secretions. Brassy cough determined by respiratory physicians is highly specific for tracheomalacia

Tpeak-Tend, Tpeak-Tend/QT ratio and Tpeak-Tend dispersion for risk stratification in Brugada Syndrome:A systematic review and meta-analysis

Background: Brugada syndrome is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF), potentially leading to sudden cardiac death (SCD). Tpeak-Tend intervals, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion have been proposed for risk stratification, but their predictive values in Brugada syndrome have been challenged recently. Methods: A systematic review and meta-analysis was conducted to examine their values in predicting arrhythmic and mortality outcomes in Brugada Syndrome. PubMed and Embase databases were searched until 1 May 2018, identifying 29 and 57 studies. Results: Nine studies involving 1740 subjects (mean age 45 years old, 80% male, mean follow-up duration was 68 ± 27 months) were included. The mean Tpeak-Tend interval was 98.9 ms (95% CI: 90.5-107.2 ms) for patients with adverse events (ventricular arrhythmias or SCD) compared to 87.7 ms (95% CI: 80.5-94.9 ms) for those without such events, with a mean difference of 11.9 ms (95% CI: 3.6-20.2 ms, P = 0.005; I2 = 86%). Higher (Tpeak-Tend)/QT ratios (mean difference = 0.019, 95% CI: 0.003-0.036, P = 0.024; I2 = 74%) and Tpeak-Tend dispersion (mean difference = 7.8 ms, 95% CI: 2.1-13.4 ms, P = 0.007; I2 = 80%) were observed for the event-positive group. Conclusion: Tpeak-Tend interval, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion were higher in high-risk than low-risk Brugada subjects, and thus offer incremental value for risk stratification

Quantum memory for entangled two-mode squeezed states

A quantum memory for light is a key element for the realization of future quantum information networks. Requirements for a good quantum memory are (i) versatility (allowing a wide range of inputs) and (ii) true quantum coherence (preserving quantum information). Here we demonstrate such a quantum memory for states possessing Einstein-Podolsky-Rosen (EPR) entanglement. These multi-photon states are two-mode squeezed by 6.0 dB with a variable orientation of squeezing and displaced by a few vacuum units. This range encompasses typical input alphabets for a continuous variable quantum information protocol. The memory consists of two cells, one for each mode, filled with cesium atoms at room temperature with a memory time of about 1msec. The preservation of quantum coherence is rigorously proven by showing that the experimental memory fidelity 0.52(2) significantly exceeds the benchmark of 0.45 for the best possible classical memory for a range of displacements.Comment: main text 5 pages, supplementary information 3 page

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

West Nile virus vector Culex modestus established in southern England

Background: The risk posed to the United Kingdom by West Nile virus (WNV) has previously been considered low, due to the absence or scarcity of the main Culex sp. bridge vectors. The mosquito Culex modestus is widespread in southern Europe, where it acts as the principle bridge vector of WNV. This species was not previously thought to be present in the United Kingdom. Findings: Mosquito larval surveys carried out in 2010 identified substantial populations of Cx. modestus at two sites in marshland in southeast England. Host-seeking-adult traps placed at a third site indicate that the relative seasonal abundance of Cx. modestus peaks in early August. DNA barcoding of these specimens from the United Kingdom and material from southern France confirmed the morphological identification. Conclusions: Cx. modestus appears to be established in the North Kent Marshes, possibly as the result of a recent introduction. The addition of this species to the United Kingdom’s mosquito fauna may increase the risk posed to the United Kingdom by WNV