Ergonomics of the Operative Field in Paediatric Minimal Access Surgery

Imperial Users onl

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Ergonomics of the operative field in paediatric minimal access surgery

This thesis studies the physical and sensorial aspects of surgical ergonomics in relation to paediatric MAS. The aims of the project are to optimise the choice of instrument size, to evaluate alternative illumination sources in paediatric MAS, and to investigate the role of shadows in potentially assisting visual perception in MAS. The ergonomic limitation of the small size of the endoscopic operative field is evaluated and a paediatric simulator is developed using anthropometric data from healthy infants to provide the experimental workspace for ergonomic studies. A study on the effect of the size of instruments on paediatric endoscopic intra-corporeal knot tying shows that using smaller instruments results in faster performance and less discomfort for the surgeon without compromising knot quality, suggesting that smaller instruments should therefore be used when operating on infants. The development of solid-state semiconductor lighting technology as an alternative to the conventional arc-lamp light source is discussed. A light-emitting diode (LED) based endoscopic illumination system, the LED endo-illuminator, is developed with favourable characteristics and fine details recognition is shown to be better compared to the conventional illumination methods. A study on distance estimation in static images does not show that the presence of endoscopic shadows improves depth perception. A further experiment shows that when the light source moves, the resultant shadow movements can give conflicting information to the viewer in the interpretation of the endoscopic scene. Therefore the light source should be stationary if endoscopic shadow is produced in the MAS illumination system. A laser-based illumination system is also developed and proof-of-concept tests show promising characteristics. Its low intensity precludes its use in large cavities but would suit the small endoscopic field in paediatric MAS.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention

Context The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning. However, its role in coronary angiography is unclear.Objective To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography.Design and Setting Prospective, randomized, double-blind, placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong.Participants Two hundred Chinese patients aged mean (SD) 68 (6.5) years with stable moderate renal insufficiency (creatinine clearance &lt;60 mL/min [1.00 mL/s]) who were undergoing elective coronary angiography with or without intervention.Intervention Participants were randomly assigned to receive oral acetylcysteine(600 mg twice per day; n = 102) or matching placebo tablets (n = 98) on the day before and the day of angiography. All patients received low-osmolality contrast agent.Main Outcome Measures Occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast administration; change in creatinine clearance and serum creatinine level.Results Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a more than 25% increase in serum creatinine level within 48 hours after contrast administration (relative risk, 0.32; 95% confidence interval [CI], 0.10-0.96; P = .03). Serum creatinine was lower in the acetylcysteine group (1.22 mg/dL [107.8 &micro;mol/L]; 95% CI, 1.11-1.33 mg/dL vs 1.38 mg/dL [122.9 &micro;mol/L]; 95% CI, 1.27-1.49 mg/dL; P = .006) during the first 48 hours after angiography. Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min (0.75 mL/s) (95% CI, 42.7-47.6 mL/min) to 58.9 mL/min (0.98 mL/s) (95% CI, 55.6-62.3 mL/min) 2 days after the contrast administration (P&lt;.001).The increase was not significant in the control group (from 42.1 to 44.1 mL/min [0.70 to 0.74 mL/s]; P = .15). The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days. There were no major treatment-related adverse events.Conclusion Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost.<br /

Effects of Sodium-Glucose Cotransporter 2 on Amputation Events: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

10.1159/000520903Pharmacology107123-13

Minimal Residual Disease-Based Risk Stratification in Chinese Childhood Acute Lymphoblastic Leukemia by Flow Cytometry and Plasma DNA Quantitative Polymerase Chain Reaction

<div><p>Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1–10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15≥10% or day-33≥0.01% but not both, II-C: day-15≥10% and day-33≥0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD≥10⁻⁴ were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients’ prognosis, with 20–35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥10⁻⁴. We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</p></div