SummaryThis study compared the quality of anaesthesia and surgical access afforded by two techniques for the administration of anaesthesia during paediatric chair dental procedures. A total of 50 ASA 1 paediatric day case patients were randomly assigned to receive anaesthesia through either the traditional Goldman nasal mask or through a nasopharyngeal airway. Patients in the nasal mask group were judged to have significantly worse airway patency (p = 0.0001) and significantly more episodes of airway obstruction (14 vs. 4; p = 0.0032) than those in the nasopharygeal airway group. Anaesthetic, surgical and oxygen saturation data did not differ significantly between the two groups. Operating conditions were universally graded as excellent in the nasopharyngeal airway group, while those in the nasal mask group were graded as excellent/good in only 79% of cases (p < 0.0001). These results suggest that better quality anaesthesia and operating conditions can be achieved by using a nasopharyngeal airway rather than the traditional nasal mask for the administration of anaesthesia to paediatric chair dental patients.Keywords Anaesthesia; dental. Equipment; nasopharyngeal airway, tracheal tube, nasal mask.. ..................................................................................... Correspondence to: Dr O. Bagshaw Accepted: 3 February 1997 Paediatric chair dental surgery is a challenge to both the anaesthetist and the surgeon. The children are outpatients, not previously assessed by an anaesthetist, unpremedicated and often frightened and uncooperative. The anaesthetist and the surgeon have to share the airway and the problems of airway obstruction, oxygen desaturation and poor surgical access are common [1, 2].The technique of using a nasopharyngeal airway for both the maintainance of airway patency and the administration of general anaesthesia is historically well described [3][4][5], but there have been no recent reports of its usefulness as an alternative to the nasal mask. Traditionally, the nasopharyngeal airway has been made from rubber and was of a fixed length, which varied depending on the size of the airway selected. Recently, we have been using this technique substituting disposable tracheal tubes for the rubber airway. These have the advantages of being single-use, the length can be readily altered and they can be easily connected to a standard anaesthetic breathing system. The aim of this study was to compare the quality of anaesthesia and surgical access afforded by these two techniques and to note any associated morbidity. MethodsLocal Ethics Committee approval for the study was obtained. The majority of children presenting for daycase chair dental surgery were eligible for inclusion in the study. Children requiring tracheal intubation for conservation work were not studied. Informed consent was obtained from a parent.A total of 50 ASA 1 children were randomly assigned to either the Nasal Mask group or the Nasopharyngeal 786ᮊ 1997 Blackwell Science Ltd Airway group. All patients were unprem...
Expression quantitative trait locus (eQTL) and genomewide association studies (GWAS) are powerful paradigms for mapping the determinants of gene expression and organismal phenotypes, respectively. However, eQTL mapping and GWAS are limited in scope (to naturally occurring, common genetic variants) and resolution (by linkage disequilibrium). Here, we present crisprQTL mapping, a framework in which large numbers of CRISPR/Cas9 perturbations are introduced to each cell on an isogenic background, followed by singlecell RNAseq (scRNAseq). crisprQTL mapping is analogous to conventional human eQTL studies, but with individual humans replaced by individual cells; genetic variants replaced by unique combinations of 'unlinked' guide RNA (gRNA)programmed perturbations per cell; and tissuelevel RNAseq of many individuals replaced by scRNAseq of many cells. By randomly introducing gRNAs, a single population of cells can be leveraged to test for association between each perturbation and the expression of any potential target gene, analogous to how eQTL studies leverage populations of humans to test millions of genetic variants for associations with expression in a genomewide manner. However, crisprQTL mapping is neither limited to naturally occurring, common genetic variants nor by linkage disequilibrium. As a proofofconcept, we applied crisprQTL mapping to evaluate 1,119 candidate enhancers with no strong a priori hypothesis as to their target gene(s). Perturbations were made by a nucleasedead Cas9 (dCas9) tethered to KRAB, and introduced at a mean 'allele frequency' of 1.1% into a population of 47,650 profiled human K562 cells (median of 15 gRNAs identified per cell). We tested for differential expression of all genes within 1 megabase (Mb) of each candidate enhancer, effectively evaluating 17,584 potential enhancertarget gene relationships within a single experiment. At an empirical false discovery rate (FDR) of 10%, we identify 128 cis crisprQTLs (11%) whose targeting resulted in downregulation of 105 nearby genes. crisprQTLs were strongly enriched for proximity to their target genes (median 34.3 kilobases (Kb)) and the strength of H3K27ac, p300, and lineagespecific transcription factor (TF) ChIPseq peaks. Our results establish the power of the eQTL mapping paradigm as applied to programmed variation in populations of cells, rather than natural variation in populations of individuals. We anticipate that crisprQTL mapping will facilitate the comprehensive elucidation of the cis regulatory architecture of the human genome. 2. CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/314344 doi: bioRxiv preprint first posted online May. 4, 2018; Main TextConsequent to an era of biochemical surveys of the human genome (such as the ENCODE Project, ( 1 ) ) and 'common variant' human genetics ( i.e. GWAS, eQTL, ( 2 , 3 ...
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