Intravenous conscious sedation in patients under 16 years of age. Fact or fiction?

Recently published guidelines on the use of conscious sedation in dentistry have published varying recommendations on the lower age limit for the use of intravenous conscious sedation. There are a large number of dentists currently providing dental treatment for paediatric patients under intravenous conscious sedation. The 18 cases reported here (age range 11-15 years), were successfully managed with intravenous conscious sedation. The experience in this paper is not sufficient evidence to recommend the wholesale use of intravenous conscious sedation in patients who are under 16 years. The fact that a range of operators can use these techniques on paediatric patients would suggest that further study should be carried out in this population. The guidance should be modified to say there is insufficient evidence to support the use of intravenous conscious sedation in children, rather than arbitrarily selecting a cut off point at age 16 years

A biomechanical analysis of weightlifting pulling derivatives and their application to performance programming

The aims of the studies within this thesis were to determine if kinetics and kinematics differences occur between weightlifting pulling derivatives across loads, and to provide greater context regarding biomechanical time series data across loads. Additionally, another aim was to determine the effect of inter-repetition rest during these exercises and establish how they may be more effectively implemented into training programmes. The results of study 1 showed that the countermovement shrug (CMS) elicited greater kinetics and kinematics than the midthigh pull (MTP) across all loads (40-140% one repetition maximum [1-RM] power clean [PC]), highlighting greater acute outputs. Similarly, the results of study 2 demonstrated greater kinetic and kinematic outputs during the hang pull (HP), across all loads (40-140% 1-RM PC), compared to the pull from the knee (PFK), highlighting the benefits of utilising the stretch shortening cycle. During the CMS (Study 3) and HP (Study 4) statistical parametric mapping was used to establish where differences exist across the entire movement, in addition to peak and mean values. Results indicated greater negative velocity at heavier loads early in the unweighting phase, and greater positive velocity at lower loads during the last 13-16% of the movement. At higher loads, the braking and propulsive phases commence at an earlier percentage of the time-normalised movement, and the total absolute durations increase with load. Study 5 was performed to examine the effect of rest redistribution (RR) on kinetics, kinematics and perceptual effort during the CMS and determined that there were no differences in kinetics and kinematics compared to traditional set (TS) configurations. Lastly, Study 6 was performed to determine the effects of RR on the kinetics, kinematics and perceptual effort during HP and showed that RR protocols did not result in greater kinetics or kinematics during the HP compared to TS, however performing 6x3 (RR72) appears to be a better in maximising velocity compared to RR protocol compared to 9x2 (RR45). The findings across the six studies provide practitioners with: 1) a greater insight into the acute differences between the MTP vs. CMS and PFK vs. HP, which may aid in exercise selection; 2) a greater understanding of how load affects the time-normalised waveform during the CMS and HP, using statistical parametric mapping, and where differences lie outside peak values; 3) RR protocols did not result in greater kinetics or kinematics during the CMS compared to TS, when total rest time was equated, likely due to the limited barbell displacement not resulting in a decline in performance during the TS.Keywords: Weightlifting pulling derivatives, rest redistribution, sports performance; time normalisatio

Variation in use of the 2-week referral pathway for suspected cancer: cross-sectional analysis

Background: A 2-Week Wait (2WW) referral pathway for earlier diagnosis of suspected cancer was introduced in England in 2000. Nevertheless, a significant proportion of patients with cancer are diagnosed by other routes (detection rate), only a small proportion of 2WW referrals have cancer (conversion rate) and there is considerable between-practice variation. Aim: This study examined use by practices of the 2WW referral in relation to all cancer diagnoses. Design and setting: A cross-sectional analysis of data extracted from the Cancer Waiting Times Database for all 2WW referrals in 2009 and for all patients receiving a first definitive treatment in the same year. Method: The age standardised referral ratio, conversion rate, and detection rate were calculated for all practices in England and the correlation coefficient for each pair of measures. The median detection rate was calculated for each decile of practices ranked by conversion rate and vice versa, performing nonparametric tests for trend in each case. Results: Data for 8049 practices, 865 494 referrals, and 224 984 cancers were analysed. There were significant correlations between referral ratio and conversion rate (inverse) and detection rate (direct). There was also a direct correlation between conversion and detection rates. There was a significant trend in conversion rate for deciles of detection rate, and vice versa, with a marked difference between the lowest and higher deciles. Conclusion: There is a consistent relationship between 2WW referral conversion rate and detection rate that can be interpreted as representing quality of clinical practice. The 2WW referral rate should not be a measure of quality of clinical care

A critique of narrative reviews of the evidence-base for ECT in depression

© The Author(s), 2022. Published by Cambridge University Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/)There has been recent debate regarding the efficacy of electroconvulsive therapy in the treatment of depression. This has been based on narrative reviews that contradict existing systematic reviews and meta-analyses. In this special article, we highlight the mistakes that occur when interpreting evidence using narrative reviews, as opposed to conventional systematic reviews and meta-analyses.Peer reviewedFinal Published versio

A comparison of kinetic and kinematic variables during the midthigh pull and countermovement shrug, across loads

This study compared kinetic and kinematic variables during the midthigh pull (MTP) and countermovement shrug (CMS). Eighteen men (age: 29.43 ± 3.95 years, height: 1.77 ± 0.08 m, body mass: 84.65 ± 18.79 kg, and 1 repetition maximum [1RM] power clean: 1.02 ± 0.18 kg·kg) performed the MTP and CMS at intensities of 40, 60, 80, 100, 120, and 140% 1RM, in a progressive manner. Peak force (PF), mean force (MF), peak velocity, peak barbell velocity (BV), peak power, (PP), mean power (MP), and net impulse were calculated from force-time data during the propulsion phase. During the CMS, PF and MF were maximized at 140% 1RM and was significantly greater than the MTP at all loads (p ≤ 0.001, Hedges g = 0.66-0.90); p < 0.001, g = 0.74-0.99, respectively). Peak velocity and BV were significantly and meaningfully greater during the CMS compared with the MTP across all loads (p < 0.001, g = 1.83-2.85; p < 0.001, g = 1.73-2.30, respectively). Similarly, there was a significantly and meaningfully greater PP and MP during the CMS, across all loads, compared with the MTP (p < 0.001, g = 1.45-2.22; p < 0.001, g = 1.52-1.92). Impulse during the CMS was also significantly greater across all loads (p < 0.001, g = 1.20-1.66) compared with the MTP. Results of this study demonstrate that the CMS may be a more advantageous exercise to perform to enhance force-time characteristics when compared with the MTP, due to the greater kinetics and kinematic values observed

General practice performance in referral for suspected cancer: influence of number of cases and case-mix on publicly reported data

Background:Publicly available data show variation in GPs’ use of urgent suspected cancer (USC) referral pathways. We investigated whether this could be due to small numbers of cancer cases and random case-mix, rather than due to true variation in performance. Methods:We analysed individual GP practice USC referral detection rates (proportion of the practice's cancer cases that are detected via USC) and conversion rates (proportion of the practice's USC referrals that prove to be cancer) in routinely collected data from GP practices in all of England (over 4 years) and northeast Scotland (over 7 years). We explored the effect of pooling data. We then modelled the effects of adding random case-mix to practice variation. Results:Correlations between practice detection rate and conversion rate became less positive when data were aggregated over several years. Adding random case-mix to between-practice variation indicated that the median proportion of poorly performing practices correctly identified after 25 cancer cases were examined was 20% (IQR 17 to 24) and after 100 cases was 44% (IQR 40 to 47). Conclusions:Much apparent variation in GPs’ use of suspected cancer referral pathways can be attributed to random case-mix. The methods currently used to assess the quality of GP-suspected cancer referral performance, and to compare individual practices, are misleading. These should no longer be used, and more appropriate and robust methods should be develope

22q11 Gene dosage establishes an adaptive range for sonic hedgehog and retinoic acid signaling during early development

We asked whether key morphogenetic signaling pathways interact with 22q11 gene dosage to modulate the severity of cranial or cardiac anomalies in DiGeorge/22q1 deletion syndrome (22q11DS). Sonic hedgehog (Shh) and retinoic acid (RA) signaling is altered in the brain and heart—clinically significant 22q11DS phenotypic sites—in LgDel mouse embryos, an established 22q11DS model. LgDel embryos treated with cyclopamine, an Shh inhibitor, or carrying mutations in Gli3Xtj, an Shh-signaling effector, have morphogenetic anomalies that are either not seen, or seen at significantly lower frequencies in control or single-mutant embryos. Similarly, RA exposure or genetic loss of RA function via heterozygous mutation of the RA synthetic enzyme Raldh2 induces novel cranial anomalies and enhances cardiovascular phenotypes in LgDel but not other genotypes. These changes are not seen in heterozygous Tbx1 mutant embryos—a 22q11 gene thought to explain much of 22q11DS pathogenesis—in which Shh or RA signaling has been similarly modified. Our results suggest that full dosage of 22q11 genes beyond Tbx1 establish an adaptive range for morphogenetic signaling via Shh and RA. When this adaptive range is constricted by diminished dosage of 22q11 genes, embryos are sensitized to otherwise benign changes in Shh and RA signaling. Such sensitization, in the face of environmental or genetic factors that modify Shh or RA signaling, may explain variability in 22q11DS morphogenetic phenotypes

Whole-body integration of gene expression and single-cell morphology

Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets