National British Orthodontic Society (BOS) Orthognathic Audit 2017-2018

OBJECTIVE: To carry out a UK national clinical audit of orthognathic acceptance criteria and information provided to orthognathic patients before treatment. DESIGN: National clinical audit. SETTING: Data collected using Bristol Online Surveys. PARTICIPANTS: Sixty-nine UK hospital orthodontic departments submitted data. METHODS: Data were collected at two time points using Bristol Online Surveys over a period of 12 months. These were before treatment at the first multidisciplinary clinic (MDT) and immediately after surgery. The data collected included: Index of Orthognathic Functional Treatment Need (IOFTN); Index of Orthodontic Treatment Need (IOTN); age; previous orthodontic treatment; attendance at an MDT; treatment times; and information provision. RESULTS: Eighty-five units agreed to take part in the audit with 69 submitting data, giving a response rate of 81%. The data from 3404 patients were uploaded, 2263 before treatment and 1141 immediately after surgery. Of patients, 91.07% had an IOFTN score of 4 or 5 and 88.73% had an IOTN score of 4 or 5. The mean age at the first MDT was 22 years in the first cohort and 21 years and 4 months in the second immediate post-surgery cohort. Of patients, 37.93% had undergone some form of previous orthodontic treatment, but only 0.28% had undergone previous orthognathic treatment; 96.93% had an MDT confirm that orthodontic treatment by itself was insufficient to adequately correct their functional symptoms. The average treatment time from bond up to surgery was 2 years and 6 months. With respect to information provision, patients received information from a number of sources, principally the British Orthodontic Society (BOS) patient information leaflets and the BOS website Your Jaw Surgery. CONCLUSIONS: In the UK, the majority of orthognathic cases fulfil the criteria for acceptance for NHS-funded orthognathic treatment, as outlined by the Chief Dental Officer's interim guidance on orthognathic treatment. This suggests any prior approval process would not be a good use of NHS resources in the commissioning of orthognathic treatment

National BOS Orthognathic Audit 2017-2018

Objective; To carry out a UK national clinical audit of orthognathic acceptance criteria and information provided to orthognathic patients prior to treatment. / Design; National clinical audit. / Setting; Data collected using Bristol Online Surveys (BOS). / Participants; 69 UK hospital orthodontic departments submitted data. / Methods; Data was collected at two time points using BOS over a period of 12 months. These were prior to treatment at the first multidisciplinary clinic (MDT), and immediately post-surgery. The data collected included: IOFTN, IOTN, age, previous orthodontic treatment, attendance at an MDT, treatment times and information provision. / Results; 85 units agreed to take part in the audit with 69 submitting data, giving a response rate of 81%. The data from 3404 patients were uploaded, 2263 prior to treatment and 1141 immediately post-surgery. 91.07% of patients had an IOFTN score of 4 or 5 and 88.73% had an IOTN score of 4 or 5. The mean age at the first MDT was 22yr in the first cohort, and 21yr and 4mo in the second immediate post-surgery cohort. 37.93% of patients had undergone some form of previous orthodontic treatment, but only 0.28% had undergone previous orthognathic treatment. 96.93% had a multidisciplinary team confirm that orthodontic treatment by itself was insufficient to adequately correct their functional symptoms. The average treatment time from bond up to surgery was 2yr and 6mo. With respect to information provision, patients received information from a number of sources, principally the BOS patient information leaflets and the BOS website Your Jaw Surgery. / Conclusions; In the UK, the majority of orthognathic cases fulfil the criteria for acceptance for NHS funded orthognathic treatment, as outlined by the Chief Dental Officer’s interim guidance on orthognathic treatment. This suggests any prior approval process would not be a good use of NHS resources in the commissioning of orthognathic treatment

Chemical Cartography of the Sagittarius Stream with Gaia

The stellar stream connected to the Sagittarius (Sgr) dwarf galaxy is the most massive tidal stream that has been mapped in the Galaxy, and is the dominant contributor to the outer stellar halo of the Milky Way. We present metallicity maps of the Sgr stream, using 34,240 red giant branch stars with inferred metallicities from Gaia BP/RP spectra. This sample is larger than previous samples of Sgr stream members with chemical abundances by an order of magnitude. We measure metallicity gradients with respect to Sgr stream coordinates $(\Lambda, B)$, and highlight the gradient in metallicity with respect to stream latitude coordinate $B$, which has not been observed before. We find $\nabla \mathrm{[M/H]} = -2.48 \pm 0.08 \times 10^{-2}$ dex/deg above the stream track ($B>B_0$ where $B_0=1.5$ deg is the latitude of the Sgr remnant) and $\nabla \mathrm{[M/H]} =- 2.02 \pm 0.08 \times 10^{-2}$ dex/deg below the stream track ($B<B_0$). By painting metallicity gradients onto a tailored N-body simulation of the Sgr stream, we find that the observed metallicities in the stream are consistent with an initial radial metallicity gradient in the Sgr dwarf galaxy of $\sim -0.1$ to $-0.2$ dex/kpc, well within the range of observed metallicity gradients in Local Group dwarf galaxies. Our results provide novel observational constraints for the internal structure of the dwarf galaxy progenitor of the Sgr stream. Leveraging new large datasets in conjunction with tailored simulations, we can connect the present day properties of disrupted dwarfs in the Milky Way to their initial conditions.Comment: 20 pages, 12 figures. Submitted to ApJ; comments welcome

Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP.

We aimed to develop an efficient, flexible and scalable approach to diagnostic genome-wide sequence analysis of genetically heterogeneous clinical presentations. Here we present G2P ( www.ebi.ac.uk/gene2phenotype ) as an online system to establish, curate and distribute datasets for diagnostic variant filtering via association of allelic requirement and mutational consequence at a defined locus with phenotypic terms, confidence level and evidence links. An extension to Ensembl Variant Effect Predictor (VEP), VEP-G2P was used to filter both disease-associated and control whole exome sequence (WES) with Developmental Disorders G2P (G2PDD; 2044 entries). VEP-G2PDD shows a sensitivity/precision of 97.3%/33% for de novo and 81.6%/22.7% for inherited pathogenic genotypes respectively. Many of the missing genotypes are likely false-positive pathogenic assignments. The expected number and discriminative features of background genotypes are defined using control WES. Using only human genetic data VEP-G2P performs well compared to other freely-available diagnostic systems and future phenotypic matching capabilities should further enhance performance

Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock protein 32

Hearing loss is often caused by death of the mechanosensory hair cells of the inner ear. Hair cells are susceptible to death caused by aging, noise trauma, and ototoxic drugs, including the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Ototoxic drugs result in permanent hearing loss for over 500 000 Americans annually. We showed previously that induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. In order to begin to translate these findings into a clinical therapy aimed at inhibiting ototoxic drug-induced hearing loss, we have now examined a pharmacological HSP inducer, celastrol. Celastrol induced upregulation of HSPs in utricles, and it provided significant protection against aminoglycoside-induced hair cell death in vitro and in vivo. Moreover, celastrol inhibited hearing loss in mice receiving systemic aminoglycoside treatment. Our data indicate that the major heat shock transcription factor HSF-1 is not required for celastrol-mediated protection. HSP32 (also called heme oxygenase-1, HO-1) is the primary mediator of the protective effect of celastrol. HSP32/HO-1 inhibits pro-apoptotic c-Jun N-terminal kinase (JNK) activation and hair cell death. Taken together, our data indicate that celastrol inhibits aminoglycoside ototoxicity via HSP32/HO-1 induction

Dense gas in nearby galaxies XVI. The nuclear starburst environment in NGC4945

A multi-line millimeter-wave study of the nearby starburst galaxy NGC 4945 has been carried out using the Swedish-ESO Submillimeter Telescope (SEST). The study covers the frequency range from 82 GHz to 354 GHz and includes 80 transitions of 19 molecules. 1.3 mm continuum data of the nuclear source are also presented. A large number of molecular species indicate the presence of a prominent high density interstellar gas component characterized by $n_{\rm H_2}\sim10^5$ cm$^{-3}$. Abundances of molecular species are calculated and compared with abundances observed toward the starburst galaxies NGC 253 and M 82 and galactic sources. Apparent is an `overabundance' of HNC in the nuclear environment of NGC 4945. While the HNC/HCN $J$=1--0 line intensity ratio is $\sim$0.5, the HNC/HCN abundance ratio is $\sim$1. While HCN is subthermally excited ($T_{\rm ex}\sim$8 K), CN is even less excited ($T_{\rm ex}\sim$3--4 K), indicating that it arises from a less dense gas component and that its $N$=2--1 line can be optically thin even though its $N$=1--0 emission is moderately optically thick. Overall, fractional abundances of NGC 4945 suggest that the starburst has reached a stage of evolution that is intermediate between those observed in NGC 253 and M 82. Carbon, nitrogen, oxygen and sulfur isotope ratios are also determined. Within the limits of uncertainty, carbon and oxygen isotope ratios appear to be the same in the nuclear regions of NGC 4945 and NGC 253. High $^{18}$O/$^{17}$O, low $^{16}$O/$^{18}$O and $^{14}$N/$^{15}$N and perhaps also low $^{32}$S/$^{34}$S ratios appear to be characteristic properties of a starburst environment in which massive stars have had sufficient time to affect the isotopic composition of the surrounding interstellar medium.Comment: 26 pages, 16 figures, accepted bt A&

EyeG2P: an automated variant filtering approach improves efficiency of diagnostic genomic testing for inherited ophthalmic disorders

BACKGROUND: Genomic variant prioritisation is one of the most significant bottlenecks to mainstream genomic testing in healthcare. Tools to improve precision while ensuring high recall are critical to successful mainstream clinical genomic testing, in particular for whole genome sequencing where millions of variants must be considered for each patient. METHODS: We developed EyeG2P, a publicly available database and web application using the Ensembl Variant Effect Predictor. EyeG2P is tailored for efficient variant prioritisation for individuals with inherited ophthalmic conditions. We assessed the sensitivity of EyeG2P in 1234 individuals with a broad range of eye conditions who had previously received a confirmed molecular diagnosis through routine genomic diagnostic approaches. For a prospective cohort of 83 individuals, we assessed the precision of EyeG2P in comparison with routine diagnostic approaches. For 10 additional individuals, we assessed the utility of EyeG2P for whole genome analysis. RESULTS: EyeG2P had 99.5% sensitivity for genomic variants previously identified as clinically relevant through routine diagnostic analysis (n=1234 individuals). Prospectively, EyeG2P enabled a significant increase in precision (35% on average) in comparison with routine testing strategies (p<0.001). We demonstrate that incorporation of EyeG2P into whole genome sequencing analysis strategies can reduce the number of variants for analysis to six variants, on average, while maintaining high diagnostic yield. CONCLUSION: Automated filtering of genomic variants through EyeG2P can increase the efficiency of diagnostic testing for individuals with a broad range of inherited ophthalmic disorders

Culture, government, and spatiality: re-assessing the 'Foucault effect' in cultural-policy studies

This article critically discusses the reconceptualization of culture and governmentality in recent Australian ‘cultural–policy studies’. It argues that the further development of this conceptualization requires a more careful consideration of the complex relations between culture, power and the different spatialities of social practices. The assumptions of this literature regarding social-democratic public institutions and the nation-state are critically addressed in the light of contemporary processes of globalization. It is argued that the use made of Foucault in this paradigm privileges a model of disciplinary power which is dependent on a particular spatialization of social subjects and technologies of the self. As a result, an uncritical application of this model to all cultural practices supports a far too coherent image of practices of ‘government’ in producing sought-after subject-effects. It is suggested that the different articulations of spatio-temporal presence and absence in cultural technologies require a less totalizing understanding of the forms of power exercised through governmental practices

A CH3CN and HCO+ survey towards southern methanol masers associated with star formation

We present the initial results of a 3-mm spectral line survey towards 83 methanol maser selected massive star-forming regions. Here we report observations of the J=5-4 and 6-5 rotational transitions of methyl cyanide (CH3CN) and the J=1-0 transition of HCO+and H13CO+. CH3CN emission is detected in 58 sources (70 %) of our sample). We estimate the temperature and column density for 37 of these using the rotational diagram method. The temperatures we derive range from 28-166 K, and are lower than previously reported temperatures, derived from higher J transitions. We find that CH3CN is brighter and more commonly detected towards ultra-compact HII (UCHII) regions than towards isolated maser sources. Detection of CH3CN towards isolated maser sources strongly suggests that these objects are internally heated and that CH3CN is excited prior to the UCHII phase of massive star-formation. HCO+ is detected towards 82 sources (99 % of our sample), many of which exhibit asymmetric line profiles compared to H13CO+. Skewed profiles are indicative of inward or outward motions, however, we find approximately equal numbers of red and blue-skewed profiles among all classes. Column densities are derived from an analysis of the HCO+ and H13CO+ line profiles. 80 sources have mid-infrared counterparts: 68 seen in emission and 12 seen in absorption as `dark clouds'. Seven of the twelve dark clouds exhibit asymmetric HCO+ profiles, six of which are skewed to the blue, indicating infalling motions. CH3CN is also common in dark clouds, where it has a 90 % detection rate.Comment: 29 pages, 16 figures. Accepted for publication in MNRAS. For associated online figures please see http://www.phys.unsw.edu.au/~crp/papers/cpurcell_2005_online.pd