Benefit From Fractionated Dose-Dense Chemotherapy in Patients With Poor Prognostic Ovarian Cancer: ICON-8 Trial

PURPOSE: An international meta-analysis identified a group of patients with advanced epithelial ovarian cancer (EOC) with a very poor survival because of two unfavorable features: (1) a poor chemosensitivity defined by an unfavorable modeled CA-125 ELIMination rate constant K (KELIM) score <1.0 with the online calculator CA-125-Biomarker Kinetics, and (2) an incomplete debulking surgery. We assumed that patients belonging to this poor prognostic group would benefit from a fractionated densified chemotherapy regimen. METHODS: The data set of ICON-8 phase III trial (ClinicalTrials.gov identifier: NCT01654146), where patients with EOC were treated with the standard three-weekly, or the weekly dose-dense, carboplatin-paclitaxel regimens and debulking primary surgery (immediate primary surgery [IPS] or delayed primary [or interval] surgery [DPS]), was investigated. The association between treatment arm efficacy, standardized KELIM (scored as favorable ≥1.0, or unfavorable <1.0), and surgery completeness was assessed by univariate/multivariate analyses in IPS and DPS cohorts. RESULTS: Of 1,566 enrolled patients, KELIM was calculated with the online model in 1,334 with ≥3 CA-125 available values (85%). As previously reported, both KELIM and surgery completeness were complementary prognostic covariates, and could be combined into three prognostic groups with large OS differences: (1) good if favorable KELIM and complete surgery; (2) intermediate if either unfavorable KELIM or incomplete surgery; and (3) poor if unfavorable KELIM and incomplete surgery. Weekly dose-dense chemotherapy was associated with PFS/OS improvement in the poor prognostic group in both the IPS cohort (PFS: hazard ratio [HR], 0.50; 95% CI, 0.31 to 0.79; OS: HR, 0.58; 95% CI, 0.35 to 0.95) and the DPS cohort (PFS: HR, 0.53; 95% CI, 0.37 to 0.76; OS: HR, 0.57; 95% CI, 0.39 to 0.82). CONCLUSION: Fractionated dose-dense chemotherapy might be beneficial for patients belonging to the poor prognostic group characterized by lower tumor chemosensitivity assessed with the online calculator CA-125-Biomarker Kinetics and incomplete debulking surgery. Further investigation in the future SALVOVAR trial is warranted

Finite Element Modelling of Soft Contact Lenses on Eye

When fitting soft contact lenses, it is impossible to visualise the tear layer below the lens in white light. In addition, being permeable, soft lenses absorbs normal fluorescein and use of high molecular fluorescein is not sensitive enough to identify subtle changes in fit. This study provides a software tool based on a Finite Element Model of the human eye, developed over a period of more than 15 years at both Dundee University and Liverpool University, that can demonstrate the fit of a known contact lens design on a particular subject’s eye through computer simulation. Using this new technique, thickness maps for the tear layer under contact lenses can be created. These maps give important feedback to the contact lens fitting and design process and have the potential to enable the full customisation of contact lenses. In addition, the model itself can demonstrate how the lens settles onto the eye during the blink process, together with rebound from the corneal surface directly after the blink

Levelling the Eye to Provide a More Accurate Ocular Shape for Comparative Analysis and Contact Lens Fitting

Topography maps play an important, increasing role in contact lenses design and fitting, particularly for large diameter lenses. Whenever an eye is measured using a topography machine, the fixation point is required to be in the machine head, around 2 to 10 cm in front of the eye. This practice induces rotation of the eye which can result in tilted maps, affecting measurement accuracy. Additionally, this measurement is necessarily around the visual axis whereas the geometric axis is more important for ocular shape measurements. It is not a simple matter to compensate for this induced error, as the eye itself has few, if any, identifiable characteristics to facilitate correct orientation. This study developed methodologies to level the eye topography data around its geometrical axis, thus providing more accurate information regarding ocular shape

Effect of Correcting Non-Orthogonal Astigmatism in Corneas with Novel Optical System

For normal eyes, astigmatism is assumed to have orthogonal axes between its optical power meridians. Irregular (non-orthogonal) astigmatism is defined as having axes with less than 90° between them. The eye condition Keratoconus generally results in non-orthogonal (NO) astigmatism and this cannot be fully corrected by conventional orthogonal optics. Objects viewed by people with significant NO astigmatism can present as multiple images or appear severely ghosted or distorted. All ophthalmic spectacle lenses and toric contact lenses assume astigmatism has orthogonal axes, making it difficult to correct NO astigmatism optically. Additionally, topography machine software imposes orthognal axes on their power map outputs, so it is not possible to easily assess the extent of NO astigmatism present in any individual eye. An investigation was undertaken to attempt to correct NO astigmatism with an appropriate optical system and assess the ffect on viausl acuity. Raw data was taken from scanning topography machines and processed to detect the natural maximum and minimum power meridians of the anterior and posterior cornea. Axial and tangential maps were created as well as power maps achieved through Light Ray Tracing A means of creating spectacle trial lenses with NO power axes was developed and three sets made to use as refraction trial lenses. The axes of each set were orientated at 80°, 70° & 60° respectively and cyl powers -1.00DC to -6.00 DC in 1.00DC steps plus an additional -0.50DC lens. Three subjects were chosen to be refracted by these lenses: two with mild keratoconus and one with longstanding, non strabismic ambylopia. They were refracted with each set of lenses, using a standard LogMAR Chart. The chart was changed randomly in between testing each set. For each subject, the refraction starting point was taken from the orthogonal spectacle prescription. The subjects were refracted with NO cyls from each set of lenses and wre asked to locate the point of optimal acuity by rotating the lens. This was independently checked by the examiner. To ensure that the subject was not experiencing a placebo effect, the lenses were randomly “flipped” during the examination. Unlike conventional cyl lenses, which present the same power meridians whichever way the lens is presented to the eye, NO lenses will present meridians at different axes when flipped which should cause an obvious difference in VA

Back-translation for discovering distant protein homologies

Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level. To cope with this situation, we propose a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. This allows us to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.Comment: The 9th International Workshop in Algorithms in Bioinformatics (WABI), Philadelphia : \'Etats-Unis d'Am\'erique (2009

Using the electronic medical record within medical undergraduate education

This paper aims to explore the potential for using a live clinical information system as a teaching tool to enhance and reinforce learning in a primary care environment, particularly regarding the enhanced use of IT systems in the primary care consultation

A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma

Bryostatin-1 is a macrocyclic lactone whose main mechanism of action is protein kinase C modulation. We investigated its activity as a weekly 24-h infusion in recurrent ovarian carcinoma. In all, 17 patients were recruited and 11 had chemotherapy-resistant disease as defined by disease progression within 4 months of last cytotoxic therapy. All were evaluable for toxicity and 14 for response. There were no disease responses and the main toxicity was myalgia

Applying a User-centred Approach to Interactive Visualization Design

Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches