Gamma interferon (IFN-?) induces expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO1) in human epithelial cells, the permissive cells for the obligate intracellular bacterium Chlamydia trachomatis. IDO1 depletes tryptophan by catabolizing it to kynurenine with consequences for C. trachomatis, which is a tryptophan auxotroph. In vitro studies reveal that tryptophan depletion can result in the formation of persistent (viable but noncultivable) chlamydial forms. Here, we tested the effects of the IDO1 inhibitor, levo-1-methyl-tryptophan (L-1MT), on IFN-?-induced C. trachomatis persistence. We found that addition of 0.2 mM L-1MT to IFN-?-exposed infected HeLa cell cultures restricted IDO1 activity at the mid-stage (20 h postinfection [hpi]) of the chlamydial developmental cycle. This delayed tryptophan depletion until the late stage (38 hpi) of the cycle. Parallel morphological and gene expression studies indicated a consequence of the delay was a block in the induction of C. trachomatis persistence by IFN-?. Furthermore, L-1MT addition allowed C. trachomatis to undergo secondary differentiation, albeit with limited productive multiplication of the bacterium. IFN-?-induced persistent infections in epithelial cells have been previously reported to be more resistant to doxycycline than normal productive infections in vitro. Pertinent to this observation, we found that L-1MT significantly improved the efficacy of doxycycline in clearing persistent C. trachomatis forms. It has been postulated that persistent forms of C. trachomatis may contribute to chronic chlamydial disease. Our findings suggest that IDO1 inhibitors such as L-1MT might provide a novel means to investigate, and potentially target, persistent chlamydial forms, particularly in conjunction with conventional therapeutics.

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INTRODUCTION: The 2008 National Mastectomy and Breast Reconstruction Audit demonstrated marked variation in the practice and outcomes of breast reconstruction in the UK. To standardise practice and improve outcomes for patients, the British professional associations developed best-practice guidelines with specific guidance for newer mesh-assisted implant-based techniques. We explored the degree of uptake of best-practice guidelines within units performing implant-based reconstruction (IBBR) as the first phase of the implant Breast Reconstruction Evaluation (iBRA) study.

METHODS: A questionnaire developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Simple summary statistics were calculated for each survey item to assess compliance with current best-practice guidelines.

RESULTS: 81 units from 79 NHS Trusts completed the questionnaire. Marked variation was observed in adherence to guidelines, especially those relating to clinical governance and infection prevention strategies. Less than half (n = 28, 47%) of units obtained local clinical governance board approval prior to offering new mesh-based techniques and prospective audit of the clinical, cosmetic and patient-reported outcomes of surgery was infrequent. Most units screened for methicillin-resistant staphylococcus aureus prior to surgery but fewer than 1 in 3 screened for methicillin-sensitive strains. Laminar-flow theatres (recommended for IBBR) were not widely-available with less than 1 in 5 units having regular access. Peri-operative antibiotics were widely-used, but the type and duration were highly-variable.

CONCLUSIONS: The iBRA national practice questionnaire has demonstrated variation in reported practice and adherence to IBBR guidelines. High-quality evidence is urgently required to inform best practice.

INTRODUCTION: The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK.

METHODS: A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined.

RESULTS: 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50-80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0-3.0) and 2.0 plastic surgeons (IQR:1.0-3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures.

CONCLUSIONS: The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored.

BACKGROUND: Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction-breast reconstruction with implants or expanders at the time of mastectomy-but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques.

METHODS: In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281.

FINDINGS: Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8-10) experienced implant loss, 372 (18%, 16-20) required re-admission to hospital, and 370 (18%, 16-20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23-27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards (<5% for re-operation, re-admission, and implant loss, and <10% for infection).

INTERPRETATION: Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction.

FUNDING: National Institute for Health Research, Association of Breast Surgery, and British Association of Plastic, Reconstructive and Aesthetic Surgeons.

Many researchers have observed that 80% -90% of tutorial utterances were in the form of questions, so-called items. However, the item quality in distance learning environment has not been discussed enough. Poor and problematic items may defeat the purpose of distance learning. Therefore, we should ensure the quality and integrity of items before storing them finally in item banks, and becoming available for distance learning systems. The traditional paper-and- pencil process for evaluating an item is performed by administering a pilot test in schools, so-called tryout. Many manual steps are needed to test the items, by trying them, in schools. This process is costly, very time–consuming endeavor, and sometimes inaccurate. In this paper, we attempt to solve this problem by introducing a new practical model for evaluating an item online. Through this model we get, on the spot, student responses and apply some techniques on these responses to identify item characteristics to ensure the quality and integrity of the item. Accordingly, this will enable us to detect and eliminate both weak and problematic items, and store only good items in the item bank, all in quick and accurate manner.

William Shakespeare has never ceased to intrigue dramatists from different ages and cultures. Throughout history, many of them attempted to engage with him in dialogues of different kinds. This book examines three "belated" works of art whose writers engage in intertextual relations with canonical Shakespearean works including plays and sonnets. These three Shakespearean mosaics belonging to three different cultures are two plays namely, the Egyptian Shakespeare Malikan (Shakespeare: A King) by Ra'fat Al -Duwayrī and the Irish Mutabilitie by Frank McGuinness and one film script, the Anglo-American Shakespeare in Love by Marc Norman and Tom Stoppard. Such examination is done to explore the reasons behind the engagement of each of the four writers in these relations, the various intertextual techniques they use and the "originality" of their texts despite their extensive borrowing from Shakespearean dramatic legacy. Observing a number of critiques and scholarly works, the author noticed the lack of thorough analysis of these three works from an intertextual perspective in relation to Shakespearean works. Such is the gap in Shakespearean scholarship which this book fills.