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Background Reversal of an international normalized ratio (INR) > 10 with vitamin K is recommended in patients experiencing bleeding; however, information on outcomes with reversal using vitamin K in non-bleeding patients is lacking. Objective To compare clinical and safety outcomes between non-bleeding patients receiving warfarin with an INR > 10 who did and did not receive a prescription for vitamin K. Patients/methods This was a retrospective cohort study conducted in an integrated health-care delivery system. Adult patients receiving warfarin therapy who experienced an INR > 10 without bleeding between 01/01/2006 and 06/30/2018 were included. Patients were assessed for an outpatient dispensing or in-office administration of vitamin K on the day of or the day after an INR > 10 and then clinically relevant bleeding, thromboembolism, all-cause mortality, and time to INR Results A total of 809 patients was included with 332 and 477 who were and were not dispensed vitamin K, respectively. Overall, mean patient age was 71.7 years, 60.1% were female and the mean INR was 10.4 at presentation. There were no differences between groups in 30-day rates of bleeding or thromboembolism (both P > .05). Patients dispensed vitamin K had a higher likelihood of mortality (15.1% versus 10.1%, P = .032, adjusted odds ratio = 1.63, 95% confidence interval 1.03 to 2.57). Overall, time to an INR Conclusion Vitamin K administration was not associated with improved clinical outcomes in asymptomatic patients with an INR > 10.

Transcriptional profiling of hematopoietic cell subpopulations has helped characterize the developmental stages of the hematopoietic system and the molecular basis of malignant and non-malignant blood diseases for the past three decades. The introduction of high-throughput RNA sequencing has increased knowledge of the full repertoire of RNA molecules in hematopoietic cells of different types, without relying on prior gene annotation. Here, we introduce the analysis of the BLUEPRINT consortium gene expression data for mature hematopoietic cells, comprising 90 total RNA and 32 small RNA sequencing experiments, from 27 different cell types. We used these data to describe the transcriptional profile of each we used guided transcriptome assembly to extend the annotation of the transcribed genome, which led to the identification of hundreds of novel non-coding RNA genes, which display a high degree of cell type specificity. We also characterized the expression of circular RNAs and found that these are also highly cell type specific. This resource refines the active transcriptional landscape of mature hematopoietic cells, highlights abundant genes and transcriptional isoforms for each cell type, and provides valuable data and visualisation tools for the scientific community working on hematological development and diseases.

Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.

Background:The COVID-19 pandemic has caught us all by surprise – from governments to individuals; the medical fraternity being no exception. It has affected all walks of life; with its immense contagiosity, diverse and intriguing pathogenesis and manifestations differing from other viruses. It has indeed left humanity in dark, unchartered waters; particularly in the early months of the pandemic.Objectives:This article shares the experience, in a Rheumatology department in a District General Hospital (DGH) in the United Kingdom, of managing patients on Biologic (b) and Targeted Synthetic (ts) DMARDs, in the midst of the COVID-19 Pandemic.Methods:All Rheumatology patients at the Princess Alexandra Hospital (PAH) in Harlow newly started on a biologic or targeted synthetic DMARD between 3rd July and 3rd Oct 2020 were identified. These patients had active inflammatory arthritis. Each patient was discussed in a dedicated Multi-Disciplinary Team (MDT) meeting and a consensus on treatment reached in-line with local and National guidelines.Figure 1.A slide presented at the Essex Rheumatology Association (ERA) meeting explaining the process adopted at the Rheumatology Department at Harlow during the peak of COVID-19 pandemic with new b/ts DMARD patients.Results:Of the 50 patients identified; 39 had Rheumatoid Arthritis, 6 had Ankylosing Spondylitis and 5 had Psoriatic Arthritis. Of these 50 patients, 5 patients decided against treatment during the stage of ‘Enhanced Verbal Consent’. These patients were flaring recurrently and were in regular contact with the department. However, they were afraid to start new Biologic treatment because of the risks of Covid-19. The breakdown of the biologic agents used in the remaining 45 patients were as follows: Adalimumab:11, Rituximab: 10, Etanercept: 9, Tofacitinib: 11, Tocilizumab SC: 3, Tocilizumab IV: 1, Sarilumab: 2, Secukinumab: 1, Infliximab: 1, Baricitinib: 1, Apremilast: 1Figure 2.Breakdown of the various b/ts DMARD agents newly started in the 45 patients between 3/7/20 - 3/10/20 at PA Hospital, Harlow, UKConclusion:The over-riding principle that guided the Department during the COVID crisis was: primum non nocere (first, do no harm). The adherence to the Case Based Discussions (CBDs) positively impacted on decision making, ensuring safe initiation of Biologic DMARDs even during the height of the pandemic. This is vital to achieve early disease remission. The MDT meetings comprising Doctors, Specialist Pharmacist and Nurse Specialists ensured prompt risk stratification of individual patients. It gave patients the opportunity to be part of the decision-making - evident in the five of the fifty patients, who opted to defer the start date of their treatments. The choice of the new Biologic agent was based on the latest National COVID-19 guidelines. The agents with the shortest half-life were selected. Moreover, patients for Rituximab were given one pulsed infusion, as opposed to two infusions. Only one of the 45 patients started on a Biologic agent over this period, either was tested positive or had symptoms suggestive of COVID-19.References:[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261974[2]https://rmdopen.bmj.com/content/6/2/e001314[3]https://www.nejm.org/doi/full/10.1056/nejmc2009567[4]https://www.jrheum.org/content/early/2020/05/13/jrheum.200527[5]https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-care-of-adult-patients-with-systemic-rheumatic-disease[6]www.england.nhs.uk/clinical-guide-rheumatology-patients-v1-19-march-2020.pdf[7]https://www.rheumatology.org.uk/practice-quality/covid-19-guidance[8]https://www.nice.org.uk/guidance/ng167/chapter/4-Treatment-considerations[9]https://www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/decision-making-and-consentAcknowledgements:We acknowledge the whole Rheumatology Dept at Harlow for their sincere team work during the COVID-19 pandemic – Sabaa Naz (Rheumatology Pharmacist), Mona Kamal Zou (Biologics Nurse Specialist), Lily Robinson (DMARD Nurse Specialist), Mary Surendran (Osteoporosis Nurse Specialist), Janet Bell (Secretary to Dr Ahmed) and Claire Stroud (Secretary to Dr Farrow).Disclosure of Interests:None declared.

Human T regulatory cells (T regs) express high levels of TNF receptor 2 (TNFR2). Ligation of TNFR2 with TNF, which can recognise both TNFR1 and TNFR2, or with a TNFR2-selective binding molecule, DARPin 18 (D18) activates canonical NF-κB signalling, assessed by IκBα degradation, and the magnitude of the response correlates with the level of TNFR2 expression. RNA-seq analysis of TNF- or D18-treated human T regs revealed that TNFR2 ligation induces transcription of NFKB2 and RELB, encoding proteins that form the non-canonical NF-κB transcription factor. In combination with IL2, D18 treatment is specific for T regs in (1) stabilising NF-κB-inducing kinase protein, the activator of non-canonical NF-κB signalling, (2) inducing translocation of RelB from cytosol to nucleus, (3) increasing cell cycle entry, and (4) increasing cell numbers. However, the regulatory function of the expanded T regs is unaltered. Inhibition of RelB nuclear translocation blocks the proliferative response. We conclude that ligation of TNFR2 by D18 enhances IL2-induced T regs proliferation and expansion in cell number through the non-canonical NF-κB pathway.

Neutrophils and monocytes provide a first line of defense against infections as part of the innate immune system. Here we report the integrated analysis of transcriptomic and epigenetic landscapes for circulating monocytes and neutrophils with the aim to enable downstream interpretation and functional validation of key regulatory elements in health and disease. We collected RNA-seq data, ChIP-seq of six histone modifications and of DNA methylation by bisulfite sequencing at base pair resolution from up to 6 individuals per cell type. Chromatin segmentation analyses suggested that monocytes have a higher number of cell-specific enhancer regions (4-fold) compared to neutrophils. This highly plastic epigenome is likely indicative of the greater differentiation potential of monocytes into macrophages, dendritic cells and osteoclasts. In contrast, most of the neutrophil-specific features tend to be characterized by repressed chromatin, reflective of their status as terminally differentiated cells. Enhancers were the regions where most of differences in DNA methylation between cells were observed, with monocyte-specific enhancers being generally hypomethylated. Monocytes show a substantially higher gene expression levels than neutrophils, in line with epigenomic analysis revealing that gene more active elements in monocytes. Our analyses suggest that the overexpression of c-Myc in monocytes and its binding to monocyte-specific enhancers could be an important contributor to these differences. Altogether, our study provides a comprehensive epigenetic chart of chromatin states in primary human neutrophils and monocytes, thus providing a valuable resource for studying the regulation of the human innate immune system.

In this study, pyrolysis of sawdust and pinewood (120–250 μm) was conducted in a drop-tube furnace (DTF) at temperatures of 900, 1100, 1300 °C and residence times of 50–600 ms in both CO2 and N2 atmospheres. The samples are fed at a rate of 5–10 g/h in a gentle flow of nitrogen (1 L/min) to ensure laminar flow. A silica tracer method has been developed to accurately determine the high temperature volatile matter yields. The elemental analysis of chars collected allowed the study of the release of nitrogen. BET surface area, scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses were also carried out to study the chars produced. Burnout tests were conducted at 1100 °C, an O2 concentration of 5% v/v in N2 and CO2 respectively, using the chars produced at the same temperature and a residence time of 200 ms. In nitrogen, the maximum volatile yield achieved was 97 wt% while in CO2, the maximum volatile yield was over 99 wt% for residence times above 200 ms, indicating virtually complete gasification of the char. These are the highest reported volatile matter yields for biomass obtained using a DTF. The release of nitrogen into the volatile phase is proportional to the yield of volatiles both for air and oxy-fuel conditions. SEM images revealed higher porosities of the DTF CO2 chars than those of N2, being consistent with their higher BET surface areas. Faster char burnout was obtained for oxy-fuel firing attributable to the CO2/char gasification reactions. The results will be useful for modeling dedicated oxy-biomass firing and co-firing systems.

Non-crystallinesulphated zirconia catalysts were synthesised by a non-aqueous and non-conventional method. The effect of varying the molar ratio of sulphating agent to zirconium source was also investigated. The samples were characterized by X-ray diffraction, Energy Dispersive X-ray (EDX), Infra-red Spectroscopy (IR),X-ray Photoelectron Spectroscopy (XPS). The surface acidity was measured by the Pyridine-DRIFTS (Diffuse Reflectance Infrared Fourier Transform Spectroscopy) technique. The structural and textural properties of the sulphated zirconia were studied. The EDX and XPS profiles suggested that both sulphated zirconia catalysts have similar zirconia and sulphate structures; however, both catalysts were amorphous. Deconvolution of their XPS O 1s spectra showed that the samples contained both oxide oxygen of zirconium and sulphate oxygen, which sample I showed a higher amount of sulphate oxygen. Adsorption of pyridine into the samples indicated that the higher amounts of Bronsted acid sites are presented in sample I with lower amount of sulphate during preparation. This opens up the possibility of controlling the degree and type of active sites on a catalyst by the amount of sulphate used for preparation. Sulphated zirconia catalyst with higher activity properties was achieved via a non-aqueous, environmentalfriendly method. The zirconia catalyst has great contribution towards energy production which is used for preparation and trans-esterification of fatty acids for production of biodiesel.

Although biomass co-firing is now well established in pulverised fuel (PF) combustion under conventional air-fired conditions, there is little information available on how biomass will behave in oxy-fuel firing. Using thermogravimetric analysis (TGA) and a drop tube furnace (DTF), this study examines the impact of co-firing biomass and coal under oxy-fuel conditions compared to normal air firing, with the emphasis on the potential catalytic effect of biomass-contained alkali and alkaline metals on coal char burnout. Individual chars and their blends prepared from sawdust, pinewood and a South African coal in a DTF and normal tube furnace under slow-heating conditions have been used in TGA char burnout tests. The results demonstrate that the coal/biomass char blends burned off significantly faster than predicted under both oxy-fuel and air-firing conditions, and this synergistic catalytic effect was found to be considerably more pronounced in oxy-fuel conditions. In particular, the DTF biomass/coal char blends from devolatilisation in CO 2 burn off approximately two times faster than those prepared in nitrogen. To further examine the catalytic effect, the raw sawdust sample was first extracted with 5 M hydrochloric (HCl) acid to remove its contained alkali and alkaline metals before the char preparation and subsequent char burnout tests. It was found that the removal of the alkali and alkaline metals led to almost complete loss of the catalytic effect as observed with the untreated sawdust derived char samples. The results indicate that biomass having relatively high contents of alkali and alkaline metals can serve as effective combustion catalysts to improve coal combustion efficiency.

Thermochemical conversion of world top crops (rice and wheat) has been extensively investigated (TGA, DTF, SEM, XRD, BET, EA), and main insights are discussed in light of materials and process kinetics. Overall, the results show that the rice husk presents lower reactivity than the wheat straw for all thermal processes regardless of the final temperatures (300 °C–1300 °C), residence times (0.6 s–300 min), and atmospheres (100–340 mL·min–1 N2/air). The higher reactivity of wheat straw is attributed not only to higher alkali and ash contents but also to differences in both silica morphology and graphitic structure after pyrolysis. Chars produced from slow pyrolysis present more homogeneous characteristics than those produced from fast pyrolysis. Combustion of the chars from slow pyrolysis (up to 900 °C) show similar kinetic parameters with activation energies, Ea, of 101.8 and 101.0 kJ·mol–1 with pre-exponential factor, A, of 4.3 × 107 and 9.6 × 107 min–1 for rice husk and wheat straw, respectively; while c...

To systematically examine and quantify the efficacy and safety of tranexamic acid in hip fracture surgery.A systematic literature search was conducted using Medline, EMBASE, AMED, CiNAHL, and the Cochrane Central Registry of Controlled Trials. Two assessors independently screened search outputs for potentially relevant articles which met the eligibility criteria. The primary outcome measure was requirement of post-operative blood transfusion. Risk of bias assessment was performed using the Cochrane Collaboration's risk of bias tool for randomized controlled trials (RCTs) and the ROBINS-I tool for observational studies. Meta-analysis was performed to estimate risk ratio (RR), risk difference (RD) and mean difference (MD) values for dichotomous and continuous data outcomes, respectively. The interpretation of each outcome was made using the GRADE approach.Of 102 studies identified, seven met the inclusion criteria including a total of 770 participants (TXA: 341; Control: 429). On meta-analysis, intravenous TXA resulted in a 46% risk reduction in blood transfusion requirement compared to a placebo/control group (RR: 0.54; 95% CI: 0.35-0.85; IThere is moderate quality evidence that TXA reduces blood transfusion in hip fracture surgery, with low quality evidence suggesting no increased risk of thrombotic events. These findings are consistent with TXA use in other orthopaedic procedures.

In the sport of curling, players sweep the ice in the front of curling stones to increase the distance that the projectiles slide. Their vigorous sweeping raises the surface temperature of the ice, thereby reducing its coefficient of friction. The change in ice temperature is dependent on the velocity that curlers sweep the ice, the downward force they apply, and the pattern that is swept. The forces and velocities applied by Olympic level curlers were recorded with an instrumented brush. Laboratory-based rubbing experiments were conducted to determine the temperature rise in ice from sweeping. A numerical model was developed on the basis of the recorded sweeping profiles and laboratory-based rubbing experiments. The model was used to compare the thermal effects of two popular sweeping styles and shows that a conventional low attack angle style is the most efficient.

The OxyCAP-UK (Oxyfuel Combustion - Academic Programme for the UK) programme was a £2M collaboration involving researchers from seven UK universities, supported by E.On and the Engineering and Physical Sciences Research Council. The programme, which ran from November 2009 to July 2014, has successfully completed a broad range of activities related to development of oxyfuel power plants. This paper provides an overview of key findings arising from the programme. It covers development of UK research pilot test facilities for oxyfuel applications; 2-D and 3-D flame imaging systems for monitoring, analysis and diagnostics; fuel characterisation of biomass and coal for oxyfuel combustion applications; ash transformation/deposition in oxyfuel combustion systems; materials and corrosion in oxyfuel combustion systems; and development of advanced simulation based on CFD modelling.

Figure 1—Conceptualization of the critical components of a nuclear magnetic resonance medical scanner. Nuclear magnetic resonance and its medical imaging offshoot, magnetic resonance imaging (MRI) are difficult subjects for most people to grasp— even conceptually. Much of the difficulty appears to lie with the technical language employed by most expert authors when they attempt to explain the subject. Although most written explanations of MRI are likely to offer the mandatory diagrams of the spinning top and magnetized protons, many surprisingly omit a picture of the imaging device itself—often leaving befuddled readers to conjure up the structural particulars of this medical marvel for themselves. In consideration of these shortcomings (and in light of the authors’ own quest for simplicity), the authors will endeavor to set forth the principles of medical magnetography in everyday language, trying to avoid jargon, physics, and mathematics. For those desiring a more rigorous explanation

BACKGROUND The pool of old cases of cataract, the expected new cases, and the shortfall in cataract surgery and consequently the numbers dying with poor vision without the benefit of cataract surgery are regarded as escalating problems worldwide. Successive governments and the professional ophthalmic bodies have not had the wherewithal to estimate the magnitude or interaction of these elements in the population of the UK. This study has collected and applied the best available epidemiological data on cataract prevalence, incidence and service utilisation, and demography to address the problem of control of the cataract pool in the population of England and Wales. METHODS Data from recent surveys undertaken by the authors, both on prevalence of vision impairing cataract and on patterns of cataract surgery, were used together with demographic and service utilisation information obtained from government departments. These were integrated within a holistic model, which was run under varied assumed levels and patterns of service provision. RESULTS The study shows that there is a serious pool of unoperated vision impairing cataract in the population aged 65 and older, reflecting a shortfall in cataract surgery. Continuing with the present level and pattern of service provision, the pool will increase to over 2.5 million by the year 2001. In addition, more than 700 000 will die with unoperated impaired vision. CONCLUSIONS Targeting of existing or new additional operations to those below the visual acuity of 6/12 will have relatively little effect on numbers dying without surgery, but should have a substantial controlling effect on the pool of vision impairing cataract in the population.

Pneumonia is a common lung disease of cattle, but because so little time is devoted to the subject in introductory radiology courses, few veterinarians feel inclined to make thoracic images of calves suspected of having pneumonia, much less render a radiographic judgment in such cases. In actuality, however, the radiographic diagnosis of pneumonia is not that difficult, provided one knows what to look for and where to look for it; and is aware of how anatomic, physiologic, and technical variations may mimic lung disease. This article provides the reader with a simple and effective integrated approach to the radiographic diagnosis of pneumonia in calves.

Conventional cardiac analysis is often a complex, tedious, and unproductive task, but by using a relatively simple technique that relies on global differences in the silhouettes of normal versus diseased hearts, one can become proficient in diagnosing congenital heart disease in young calves. The essentials of the method are described in this article, along with many radiographic examples.

A series of radiographs are presented to illustrate the relevant anatomy and radiology of infections of the digital region. The typical reaction to infection of bones, joints, and other soft tissues are described as they relate specifically to cattle.

Pharyngeal puncture caused by a balling gun can lead to severe infection and abscessation. Dysphagia and dyspnea soon follow if the injury goes undetected. Radiographically, pharyngeal compression, laryngeal and tracheal displacement, and extensive gas accumulation throughout the throat and cranial neck regions characterize these injuries. This article describes the typical radiographic appearance of this unique form of trauma.

Gas is probably the best single radiographic indicator of infection in cattle, especially in and around the digits. With high quality images and a high-intensity light, gas may be detected in small pockets within the soft tissues, effacing bone surfaces, or within joints. This article illustrates the varied radiographic appearances of gas associated with infection, and the radiographic projections that optimize its detection.

Imaging one or more reticular foreign bodies is only the first step in confirming a diagnosis of reticulitis. One must then determine whether or not any of the observed objects are trapped or imbedded in the reticular folds, piercing the reticular wall, or lying innocently within the reticular lumen. This article provides a simple strategy for differentiating between these various diagnostic possibilities.

Objective: To estimate the magnitude of serious eye disorders and of visual impairment in a defined elderly population of a typical metropolitan area in England, and to assess the frequency they were in touch with, or known to, the eye care services. Design: Cross sectional survey using two stage cluster random sampling. Setting: General practices in north London. Subjects: Random sample of people aged 65 and older, drawn from a defined population of elderly people registered with 17 general practice groups. Main outcome measures: Proportions and population prevalence estimates were determined for visual acuity, assessed with the person9s own spectacles (if any), classified into four categories: prevalence of cataract, age related macular degeneration, and refractive error causing visual impairment and of definite primary open angle glaucoma; and status of contact with eye services. Results: 1547 of 1840 (84%) eligible people were examined. The population prevalence of bilateral visual impairment (visual acuity Conclusions: Untreated visual impairment and eye disorders affect a substantial proportion of people aged 65 years and older. These findings should contribute to the setting up of future strategies for preservation of sight and eye health services in general. Key messages Data have not been adequate to reliably estimate the extent of visual impairment and serious eye disease in metropolitan areas in Britain Data from north London shows that 30% of a sample of the population aged 65 or older are visually impaired in both eyes More than 72% of the bilateral visual impairment was potentially remediable by surgery or glasses, nearly one in three people had visually impairing cataract, and 88% of these people were not in touch with eye services Eye problems were more prevalent in people living in relatively underprivileged areas

IFN-γ levels are increased in chronic obstructive airway disease (COPD) patients compared with healthy subjects and are further elevated during viral exacerbations. IFN-γ can 'prime' macrophages to enhance the response to toll-like receptor (TLR) ligands, such as LPS. The aim of this study was to examine the effect IFN-γ on corticosteroid sensitivity in alveolar macrophages (AM).AM from non-smokers, smokers and COPD patients were stimulated with IFN-γ and/or LPS with or without dexamethasone. IL-6, TNF-α and IFN-γ-induced protein 10 kDa (IP-10) levels were measured by elisa, and Western blots were used to investigate the IFN-γ-stimulated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway. Real-time PCR and flow cytometry were used to investigate TLR levels following IFN-γ treatment.In all three subject groups, IFN-γ alone had no effect on IL-6 and TNF-α production but enhanced the effects of LPS on these cytokines. In contrast, IFN-γ alone increased the production of IP-10. IFN-γ increased TLR2 and TLR4 expression in AM. Cytokine induction and STAT1 activation by IFN-γ were insensitive to dexamethasone for all groups. The inhibition of JAK and STAT1 repressed all these IFN-γ effects.Our results demonstrate that IFN-γ-induced STAT-1 signalling is corticosteroid resistant in AMs, and that targeting IFN-γ signalling by JAK inhibitors is a potentially novel anti-inflammatory strategy in COPD.

This report describes the views of members of the public to proposals to charge for a given list of NHS services for which no charges are currently made. The questions were part of a survey conducted in Cardiff in 1986. The majority of respondents would agree with the suggested charges being levied. This agreement spanned all sections of society. Despite the majority in favour, the sample was divided with a third of respondents being strongly for nearly all the charges and a quarter being strongly against all or all but one of the charges. Most respondents to the survey are judging each charge as a separate issue rather than indicating either approval or disapproval for all cases. If charges for services were to be introduced there could be majority agreement but each charge would have to be considered as a separate issue.

Introduction and objectives Tuberculosis cohort audit (TBCA) was introduced across the North West in 2012 as recommended by NICE. The approach taken and the outcome measures of the 1,515 TB cases reviewed are presented in a companion abstract. TBCA over a large geographical area has not undergone formal qualitative evaluation in the UK. We conducted a qualitative evaluation to explore perceptions about implementation and impact of TBCA in the North West. Methods One researcher conducted face to face, semi-structured, recorded interviews between 06/01/14 and14/03/14 with 26 purposively sampled respondents from three groups involved in TBCA: (a) TB nurse specialists; (b) Consultant physicians; (c) Public health practitioners. Transcripts were analysed descriptively and thematically using the Framework Method. Themes were triangulated with eight key informants from the TBCA Steering Group. Results Four themes were identified: 1. Preconceptions: Participants were optimistic about the potential of audit to improve practice but worried about time demands and scrutiny from colleagues. 2. Experience of TBCA: All groups felt engaged and appreciated TBCA. Nurses requested more engagement from consultant colleagues. Fears about time demands and scrutiny were not realised. 3. Changes as a result of TBCA : Improvements to practice were identified including harmonisation of approaches, increased HIV testing, and improved documentation. TBCA was felt to provide peer support and learning through discussion and a no-blame atmosphere. 4. Looking Ahead: Suggestionsfor further improvement were captured, such as more in-depth discussion around complex cases. If TBCA were to be discontinued (e.g. because of funding contraints), adverse consequences were predicted: e.g. disappointed and disenfranchised professionals, financial and patient harms. Conclusions Overall, TBCA in the North West has led to the development of a unique and valuable community of practice. The interchange of experience and ideas across a large number of teams and professionals has enhanced mutual respect between different roles and a shared sense of purpose. TBCA is appreciated by health professionals who participate. Continuing success will require increased engagement of consultant physicians and public health practitioners, a secure an ongoing funding stream and establishment of reporting mechanisms within the new commissioning structures.

The lead paper, "Healthcare-Associated Infections as Patient Safety Indicators," written by Gardam, Lemieux, Reason, van Dijk and Goel, puts forward the design of healthcare facilities as one of many strategies to improve patient safety with respect to healthcare-associated infections. This commentary explores some of the issues in balancing infection prevention and control priorities with other needs and values brought to the design process. This balance is challenged not only by a lack of supporting evidence but also by the superficial nature in which infection prevention and control are often discussed within a design context. For the physical environment to support any patient safety initiative, the design of the processes must be developed in conjunction with that of the physical environment so that compliance can be natural and convenient. Finally, consideration is given to the value of documenting decision-making related to infection prevention and control in facility design and ongoing assessments of existing facilities.