Background This paper describes a web based tool that uses a combination of sonification and an animated display to inquire into the SARS-CoV-2 genome. The audio data is generated in real time from a variety of RNA motifs that are known to be important in the functioning of RNA. Additionally, metadata relating to RNA translation and transcription has been used to shape the auditory and visual displays. Together these tools provide a unique approach to further understand the metabolism of the viral RNA genome. This audio provides a further means to represent the function of the RNA in addition to traditional written and visual approaches. Results Sonification of the SARS-CoV-2 genomic RNA sequence results in a complex auditory stream composed of up to 12 individual audio tracks. Each auditory motive is derived from the actual RNA sequence or from metadata. This approach has been used to represent transcription or translation of the viral RNA genome. The display highlights the real-time interaction of functional RNA elements. The sonification of codons derived from all three reading frames of the viral RNA sequence in combination with sonified metadata provide the framework for this display. Functional RNA motifs such as transcription regulatory sequences and stem loop regions have also been sonified. Using the tool, audio can be generated in real-time from either genomic or sub-genomic representations of the RNA. Given the large size of the viral genome, a collection of interactive buttons has been provided to navigate to regions of interest, such as cleavage regions in the polyprotein, untranslated regions or each gene. These tools are available through an internet browser and the user can interact with the data display in real time. Conclusion The auditory display in combination with real-time animation of the process of translation and transcription provide a unique insight into the large body of evidence describing the metabolism of the RNA genome. Furthermore, the tool has been used as an algorithmic based audio generator. These audio tracks can be listened to by the general community without reference to the visual display to encourage further inquiry into the science.

Draeger mentions herd immunity while discussing compulsory vaccination.1 The concept of herd immunity arises from ordinary differential equation models, with the population at risk mixing randomly. The model assumes that children in rural Scotland, Wales, or Cornwall have the same chance of contact with a person with measles in London as do children in Westminster. Keeling and Eames showed that the structure of contact networks …

Background: We sought to reduce healthcare-associated infections (HCAIs) through the application of complexity science. Objective: To confirm incidental findings that altering the structure of microbiology reports with targeted education led to better utilisation of laboratory resources, while participating in efforts to reduce HCAI. Methods: We adopted a different approach to laboratory result authorisation, using narrative to engage the clinicians and induce behavioural change. Subsequent educational opportunities emphasised key messages. Findings/Results: Positive urine means calculated by the analysis tool numbered 2179/month throughout the study period. Negative urines started at 5576/month, reduced to 5134/month in November 2014 and to 4602/month in April 2016, coinciding with our changes. Opportunity costs were saved. Discussion: The changes in both policy and reporting were contemporaneous with a decline in negative samples. There were no significant changes in the number of positive specimens. The efficiency and effectiveness of the laboratory was improved and resources released: £145,000 ($182,000) for a resident population of 384,000. This suggests an annual release of about £25 million ($31 million) may be possible in the UK and £122 million ($155 million) in the USA.

BACKGROUND:The homozygous yeast deletion library includes approximately 4800 diploid strains each containing one deleted non-essential gene. Hundreds of publications have arisen through experimentation using this genome-wide biological resource. As part of this work over 677 genesets have been collated from these experiments representing the phenotypic responses of the library to a diverse set of chemical and physical challenges.DESCRIPTION:A website called the Saccharomyces cerevisiae Homozygous Deletion Library Tools (ScHo DeLiTo-96) has been developed with the primary goal of browsing and identifying genes shared between these responsive phenotypes (available at yeastdb.org ). Geneset comparisons have been performed for each phenotype against all others to identify common genes. Genesets and other curated information are stored in a relational database and a website interface allows users to query and browse the data in an intuitive way to reveal commonality between selected phenotypic responses. The most commonly occurring genes in all of the stored phenotypes are highly over-represented in the GO slim term "cellular ion homeostasis" indicating that genes shared between phenotypes may highlight a common cellular response. Additionally, user derived genesets can be uploaded and intersected against the stored data to reveal common responses which may otherwise have been obscure.CONCLUSION:These tools provide a simple method to perform niche enquiries between datasets derived from the yeast deletion library.

BACKGROUND:Cisplatin has been widely used for the treatment of cancer and its antitumour activity is attributed to its capacity to form DNA adducts, predominantly at guanine residues, which impede cellular processes such as DNA replication and transcription. However, there are associated toxicity and drug resistance issues which plague its use. This has prompted the development and screening of a range of chemotherapeutic drug analogues towards improved efficacy. The biological properties of three novel platinum-based compounds consisting of varying cis-configured ligand groups, as well as a commercially supplied compound, were characterised in this study to determine their potential as anticancer agents.METHODS:The linear amplification reaction was employed, in conjunction with capillary electrophoresis, to quantify the sequence specificity of DNA adducts induced by these compounds using a DNA template containing telomeric repeat sequences. Additionally, the DNA interstrand cross-linking and unwinding efficiency of these compounds were assessed through the application of denaturing and native agarose gel electrophoresis techniques, respectively. Their cytotoxicity was determined in HeLa cells using a colorimetric cell viability assay.RESULTS:All three novel platinum-based compounds were found to induce DNA adduct formation at the tandem telomeric repeat sequences. The sequence specificity profile at these sites was characterised and these were distinct from that of cisplatin. Two of these compounds with the enantiomeric 1,2-diaminocyclopentane ligand (SS and RR-DACP) were found to induce a greater degree of DNA unwinding than cisplatin, but exhibited marginally lower DNA cross-linking efficiencies. Furthermore, the RR-isomer was more cytotoxic in HeLa cells than cisplatin.CONCLUSIONS:The biological characteristics of these compounds were assessed relative to cisplatin, and a variation in the sequence specificity and a greater capacity to induce DNA unwinding was observed. These compounds warrant further investigations towards developing more efficient chemotherapeutic drugs.

BACKGROUND:DNA Sonification refers to the use of an auditory display to convey the information content of DNA sequence data. Six sonification algorithms are presented that each produce an auditory display. These algorithms are logically designed from the simple through to the more complex. Three of these parse individual nucleotides, nucleotide pairs or codons into musical notes to give rise to 4, 16 or 64 notes, respectively. Codons may also be parsed degenerately into 20 notes with respect to the genetic code. Lastly nucleotide pairs can be parsed as two separate frames or codons can be parsed as three reading frames giving rise to multiple streams of audio.RESULTS:The most informative sonification algorithm reads the DNA sequence as codons in three reading frames to produce three concurrent streams of audio in an auditory display. This approach is advantageous since start and stop codons in either frame have a direct affect to start or stop the audio in that frame, leaving the other frames unaffected. Using these methods, DNA sequences such as open reading frames or repetitive DNA sequences can be distinguished from one another. These sonification tools are available through a webpage interface in which an input DNA sequence can be processed in real time to produce an auditory display playable directly within the browser. The potential of this approach as an analytical tool is discussed with reference to auditory displays derived from test sequences including simple nucleotide sequences, repetitive DNA sequences and coding or non-coding genes.CONCLUSION:This study presents a proof-of-concept that some properties of a DNA sequence can be identified through sonification alone and argues for their inclusion within the toolkit of DNA sequence browsers as an adjunct to existing visual and analytical tools.

There is no doubt that the majority of the public in scotland has a desire for both a separate local focus (by repeatedly voting heavily for a party that believes in independence and installing it in a position of power in holyrood), and at the same time a collective approach by supporting continuing membership of the european union. Thus the actions of the scottish population seem to demonstrate the central feature of complexity science, namely that complex adaptive systems allow beneficial complex organised behaviour to emerge from a small limited set of interacting deterministic rules.

Background: The anti-tumour activity of cisplatin is thought to be a result of its capacity to form DNA adducts which prevent cellular processes such as DNA replication and transcription. These DNA adducts can effectively induce cancer cell death, however, there are a range of clinical side effects and drug resistance issues associated with its use. In this study, the biological properties of three novel dinuclear platinum-based compounds (that contain alkane bridging linkers of eight, ten and twelve carbon atoms in length) were characterised to assess their potential as anticancer agents.Methods: The properties of these compounds were determined using a DNA template containing seven tandem telomeric repeat sequences. A linear amplification reaction was used in combination with capillary electrophoresis to quantify the sequence specificity of DNA adducts formed by these compounds at base pair resolution. The DNA cross-linking ability of these compounds was assessed using denaturing agarose gel electrophoresis and cytotoxicity was determined in HeLa cells using a colorimetric cell viability assay.Results: The dinuclear compounds were found to preferentially form DNA adducts at guanine bases and they exhibited different damage intensity profiles at the telomeric repeat sequences compared to that of cisplatin. The dinuclear compounds were found to exhibit a low level of cytotoxicity relative to cisplatin and their cytotoxicity increased as the linker length increased. Conversely, the interstrand cross-linking efficiency of the dinuclear compounds increased as the linker length decreased and the compound with the shortest alkane linker was six-fold more effective than cisplatin.Conclusions: Since the bifunctional compounds exhibit variation in sequence specificity of adduct formation and a greater ability to cross-link DNA relative to cisplatin they warrant further investigation towards the goal of developing new cancer chemotherapeutic agents.

Twenty years ago Trends in Biochemical Sciences published an innovative origami template for modeling the DNA double helix. Presented here are adaptations of this, including a chemical structure designed for transparent acetate, plus hybrid DNA/RNA, RNA hairpin, and single-stranded models. These models are useful teaching tools for understanding the 3D structure of DNA.

One problem that Oliver did not highlight in his discussion of preventing hospital admission was the apparent contradiction inherent in the business model of hospitals.1 The fundamental aim of businesses is to increase their …

OBJECTIVES/HYPOTHESIS:To examine postoperative hemorrhage following adenoidectomy.STUDY DESIGN:Prospective multicenter observational study.METHODS:The Surgical Instrument Surveillance Programme (SISP) was established in 2003 to monitor tonsil and adenoid surgery in all hospitals in Wales. Data were examined between April 1, 2003 and June 30, 2008, for risk factors that may contribute to primary (R1) or secondary (R2) postoperative hemorrhage from the adenoid bed, of a severity sufficient to require a return to the operating room.RESULTS:There were 5,588 procedures included, of which 4,225 included simultaneous tonsillectomy. The study included 2,903 (52%) males with a median age of 5.8 years (interquartile range [IQR], 4.5-7.7 years) and 2,685 (48%) females with a median age of 6.5 years (IQR, 5.0-9.1 years). There were 22 patients (0.4%; confidence interval [CI], 0.2-0.6) who returned to the operating room with a postoperative hemorrhage arising from the adenoid bed. These were exclusively R1 hemorrhage; there were no instances of R2 hemorrhage (0.0%; CI, 0.0-0.1). No specific risk factors for R1 hemorrhage could be identified. There were 38 patients in the adenotonsillectomy group who returned to operating room with a postoperative hemorrhage arising from the tonsil bed (0.5%; CI, 0.3-0.8). R1 was seen in 22 patients (0.5%; CI, 0.3-0.8) and R2 in 16 patients (0.4%; CI, 0.2-0.6).CONCLUSIONS:Adenoidectomy appears to be primarily a procedure performed in childhood. The rate of R1 hemorrhage following adenoidectomy is one in 200 (0.5%) and is similar to the R1 hemorrhage rate for tonsillectomy. R2 hemorrhage following an adenoidectomy appears to be extremely rare. In children, the risk of a serious primary hemorrhage following an adenotonsillectomy is double that of either procedure when performed alone.

Stone and colleagues’ results are consistent with mathematical models of hospital transmission of meticillin resistant Staphylococcus aureus (MRSA).1 This can be shown using Cooper and colleagues’ model, whereby transmission within hospital is described by an effective contact rate parameter between susceptible and infectious people. Improved hygiene conditions reduce the probability that contact between people results …

BackgroundWales has higher rates of smoking in pregnancy than does any other UK country. 33% of women in Wales smoked before or during their pregnancy compared with 26% in the UK, and 16% of women in Wales continued to smoke throughout their pregnancy. There is guidance from the UK National Institute for Health and Clinical Excellence (NICE) for smoking cessation during and after pregnancy, but a full health economic analysis of the costs and benefits of smoking cessation during pregnancy is limited by the absence of comprehensive data for the wider public health effects for the mother, child, and family associated with smoking cessation during pregnancy. We aim to provide a conceptual framework for a model to estimate the wider public health effects of smoking cessation during pregnancy.MethodsWe will construct a model and populate it with parameters estimated from the Wales Electronic Cohort of Children (WECC). WECC contains anonymised records of the 804 290 children living in Wales between 1990 and 2008. It is compiled from eight different datasets, which are record linked with the Secure Anonymised Information Linkage (SAIL) instrument. This analysis will focus on the effect of smoking during pregnancy on several birth outcomes (gestational age, birthweight, stillbirth), including the effects of maternal age and social deprivation measured with Townsend scores. This model will allow us to explore the effect of smoking in pregnancy on birth outcomes and predict where an increase in uptake of smoking cessation services would have most effect. Use of the linked datasets enables us to include a range of variables and outcomes by linking health and social care sources. This approach will help us to make the best use of resources in Wales to have maximum effect on the public health effects of smoking in pregnancy. Programme budgeting and marginal analysis will complement the modelling, informing where current resources could be best targeted.FindingsDescriptive analysis from the WECC data will be reported later in 2012 and used to populate the model, which will be developed by spring, 2013.InterpretationOnce developed, the model can be extended to include early years outcomes for the child beyond the time of birth, including asthma and upper respiratory tract infections, and developmental outcomes such as school readiness. The basis of this model can then be used for other public health areas—eg, the effect of maternal obesity on outcomes for the mother and child.FundingNone.

Clinical OtolaryngologyVolume 36, Issue 3 p. 281-282 CORRESPONDENCE: LETTERS Re: Improvement in quality of life by adenotonsillectomy in children with adenotonsillar disease D. Owens, D. Owens Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorR. Fox, R. Fox Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorW. Harrison, W. Harrison Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorM. Temple, M. Temple Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorA. Tomkinson, A. Tomkinson Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this author D. Owens, D. Owens Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorR. Fox, R. Fox Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorW. Harrison, W. Harrison Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorM. Temple, M. Temple Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this authorA. Tomkinson, A. Tomkinson Department of Otolaryngology, University Hospital of Wales, Wales, Cardiff, UK.E-mail: alnwick2@yahoo.comSearch for more papers by this author First published: 13 July 2011 https://doi.org/10.1111/j.1749-4486.2011.02301.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume36, Issue3June 2011Pages 281-282 RelatedInformation

We describe the first confirmed person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus that occurred in a hematology unit in the United Kingdom. Eleven cases of (H1N1) 2009 virus infection were identified, of which, ten were related as shown by sequence analysis of the hemagglutinin and neuraminidase genes. H275Y analysis demonstrated that 8 of 10 case patients had oseltamivir-resistant virus, with 4 of 8 case patients infected by direct transmission of resistant virus. Zanamivir should be considered as first-line therapy for influenza in patients with lymphopenic hematological conditions and uptake of influenza vaccination encouraged to further reduce the number of susceptible individuals.

OBJECTIVES/HYPOTHESIS:To identify the main risk factors associated with postoperative hemorrhage following tonsillectomy. STUDY DESIGN:Prospective multicenter observational study. METHODS:The Surgical Instrument Surveillance Programme (SISP) was established in 2003 to monitor tonsil and adenoid surgery and the associated complications in all hospitals in Wales. Data were examined between April 1, 2003, and June 30, 2008, by using binary logistic regression, for risk factors that may contribute to primary (R1) or secondary (R2) postoperative hemorrhage of a severity sufficient to require a return to the operating theater. RESULTS:A total of 17,480 procedures were included. Patients aged ≥12 years were 1.5 (1.0-2.1; P < .05) and 3 times (2.2-4.9; P < .0001) more likely to experience R1 and R2 complications, respectively. There were 2.5 times as many females as males aged ≥12 years who underwent tonsillectomy, but males were almost twice as likely to experience R1 (1.4-2.8), P < .0001, or R2 (1.2-2.5), P < .001, postoperative hemorrhage. There was a 1.9-fold increased likelihood of R1 (1.1-3.3), P < .05, with the most junior surgeon, and no relationship with R2. All techniques that used heat had a significantly greater adjusted odds of R2 as compared with cold dissection, with odds ranging from 2.7 (1.5-4.7), P < .001, for dissection plus bipolar diathermy and ties, to 13.0 (5.8-29.1), P < .0001, with coblation when used with other techniques. No additional risk was associated with specified single-use instruments. CONCLUSIONS:Patient age and sex and operative technique were the most significant factors affecting the risk and timing of serious postoperative hemorrhage, with no additional risk associated with the use of specified single-use instruments.

Lenzer and Brownlee highlight the potential value for postmarketing surveillance,1 but this is true not only for “complex” or new devices. The UK government’s decision in 2001 to replace reusable tonsillectomy instruments with single use devices, because of the risk from variant Creutzfeldt-Jakob disease, is a lesson in point. These were not …