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

Patients, family members and healthcare professionals’ top ten research priorities for adults receiving home parenteral nutrition for malignant or benign disease

Background &amp; aims: Home parenteral nutrition (HPN) is the primary treatment for chronic intestinal failure (CIF) due to non-malignant disease and is increasingly used in patients with a diagnosis of cancer. This project engaged with patients, family members and healthcare professionals to ascertain what questions they want researched. Methods: This study followed the five-stage process of the James Lind Alliance that involved (1) setting up a steering group, (2) carrying out an initial survey to gather participants’ questions, (3) data processing, (4) an interim priority setting survey and (5) final priority setting workshop. Surveys were translated and back translated into Italian, Danish and French. Results: The project was delivered by an international steering committee with representation from Denmark, Italy, the United Kingdom and United States consisting of three patients, six healthcare professionals and facilitated by University researchers. For the first survey, 633 questions were submitted by 292 respondents from 12 countries. There were 79 questions removed as out of scope or already in the published literature. Responses were collated into two interim surveys of 41 questions for benign CIF and 13 questions for HPN and cancer. In the second survey, 216 respondents prioritised their top ten questions. The ordering from the cancer and HPN survey was taken as definitive; top priorities were quality of life, survival, when to commence HPN, using HPN with anti-cancer treatments, access barriers, measuring benefit and ethical implications. For CIF with benign disease, 18 questions were discussed in two workshops attended by 13 patients and 7 healthcare professionals. The questions were ranked using a modified nominal group technique; the top research priorities were prevention and treatment of liver disease, improving central infusion lines, oral absorption, avoiding long-term negative consequences, vascular access, side effects, line infections, decreasing stoma output, quality of life and sleep. Conclusions: Priorities identified will assist researchers to focus on research questions important to patients, family members and healthcare professionals