Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m−2 twice daily) days 1–14 every 3 weeks and MMC (7 mg m−2 IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40–77), and 23 patients (78%) were performance status 0–1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6–6.2). Median overall survival was 9.3 months (95% CI: 6.9–11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule

The Influence of Mirror-Visual Feedback on Training-Induced Motor Performance Gains in the Untrained Hand

The well-documented observation of bilateral performance gains following unilateral motor training, a phenomenon known as cross-limb transfer, has important implications for rehabilitation. It has recently been shown that provision of a mirror image of the active hand during unilateral motor training has the capacity to enhance the efficacy of this phenomenon when compared to training without augmented visual feedback (i.e., watching the passive hand), possibly via action observation effects [1]. The current experiment was designed to confirm whether mirror-visual feedback (MVF) during motor training can indeed elicit greater performance gains in the untrained hand compared to more standard visual feedback (i.e., watching the active hand). Furthermore, discussing the mechanisms underlying any such MVF-induced behavioural effects, we suggest that action observation and the cross-activation hypothesis may both play important roles in eliciting cross-limb transfer. Eighty participants practiced a fast-as-possible two-ball rotation task with their dominant hand. During training, three different groups were provided with concurrent visual feedback of the active hand, inactive hand or a mirror image of the active hand with a fourth control group receiving no training. Pre- and post-training performance was measured in both hands. MVF did not increase the extent of training-induced performance changes in the untrained hand following unilateral training above and beyond those observed for other types of feedback. The data are consistent with the notion that cross-limb transfer, when combined with MVF, is mediated by cross-activation with action observation playing a less unique role than previously suggested. Further research is needed to replicate the current and previous studies to determine the clinical relevance and potential benefits of MVF for cases that, due to the severity of impairment, rely on unilateral training programmes of the unaffected limb to drive changes in the contralateral affected limb

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (£2132) and tegafur with uracil (£3385) were lower than costs for the intravenous Mayo regimen (£3593) and infusional regimens on the de Gramont (£6255) and Modified de Gramont (£3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens

High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary

BACKGROUND:Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. METHODOLOGY/PRINCIPAL FINDINGS:The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). CONCLUSIONS/SIGNIFICANCE:Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population

What is the impact of a national postgraduate medical specialist education reform on the daily clinical training 3.5 years after implementation? A questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Many countries have recently reformed their postgraduate medical education (PGME). New pedagogic initiatives and blueprints have been introduced to improve quality and effectiveness of the education. Yet it is unknown whether these changes improved the daily clinical training. The purpose was to examine the impact of a national PGME reform on the daily clinical training practice.</p> <p>Methods</p> <p>The Danish reform included change of content and format of specialist education in line with outcome-based education using the CanMEDS framework. We performed a questionnaire survey among all hospital doctors in the North Denmark Region. The questionnaire included items on educational appraisal meetings, individual learning plans, incorporating training issues into work routines, supervision and feedback, and interpersonal acquaintance. Data were collected before start and 31/2 years later. Mean score values were compared, and response variables were analysed by multiple regression to explore the relation between the ratings and seniority, type of hospital, type of specialty, and effect of attendance to courses in learning and teaching among respondents.</p> <p>Results</p> <p>Response rates were 2105/2817 (75%) and 1888/3284 (58%), respectively. We found limited impact on clinical training practice and learning environment. Variances in ratings were hardly affected by type of hospital, whereas belonging to the laboratory specialities compared to other specialties was related to higher ratings concerning all aspects.</p> <p>Conclusions</p> <p>The impact on daily clinical training practice of a national PGME reform was limited after 31/2 years. Future initiatives must focus on changing the pedagogical competences of the doctors participating in daily clinical training and on implementation strategies for changing educational culture.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation