Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.

BackgroundCysteamine has improved survival and prognosis in cystinosis. Increasing numbers of patients reach adulthood and face new challenges such as compliance that wanes over time. The aim of this study was to evaluate adherence to cysteamine treatment in a group of cystinotic patients in Spain in an attempt to identify potential therapy pitfalls and improve the overall care of affected individuals. Despite the impact of cysteamine on prognosis, there is a paucity of data regarding adherence.MethodThirty-four cystinotic patients (21 male) 38% ≥18 years were enrolled in a voluntary, anonymous survey. Replies were obtained from patients (15/34), mothers (11/34), fathers (4/34) and both parents (4/34).ResultsPatient age (median and interquartile range) at diagnosis was 1 year (0.57–1), and patient age at Cystagon® initiation was also 1 year (0.8–1.8). Sixteen (47%) were kidney transplant (KTx) recipients; six were retransplanted. Age at first KTx 10 years (8.7–13.7). Patient understanding of multiorgan involvement in cystinosis: 4.1 organs reported; eye 97% and kidney 91%. Cysteamine was given by mother (100%) and father (83%) in <11 year olds, or self-administered (94%) in ≥11 year olds. Four daily doses in 89% versus 56% in <11 year olds or ≥11 year olds, with fixed schedule in 94% versus 50% in <11 or ≥11 year olds and progressive loss of reminders over time. Furthermore, 44% complained of unpleasant smell. Motivation for treatment compliance was 100% versus 40% in <11 versus ≥11 year olds, respectively. Disease impact in patients <18 years is as follows: school (29%), social (14%), ‘feeling different’ (10%); in patients ≥18 years: ‘feeling different’ (62%), professional (39%) and job absenteeism (31%). Referring physician: paediatric nephrologist (94%) and nephrologist (63%) in <11 versus ≥11 year olds. Ophthalmological follow-up: 83% versus 38% in <11 versus ≥11 year olds. Patient opinion of physician expertise: paediatric nephrologist (94%) and nephrologist (44%). New treatment options (65%) and better information (42%) were demanded to improve adherence.ConclusionTreatment with Cystagon is effective in young patients. However, adherence diminishes over time in adolescents and adults despite disease impact. Strategies such as better information on the disease, patient self-care promotion and facilitated transition to adult healthcare services are required to improve compliance and the clinical management of cystinosis.

Ectopic or heterotopic pancreas is defined as the presence of pancreatic tissue in an anatomical place not related to the pancreas, being it most frequent locations the stomach and small bowel. Its finding in the gallbladder is exceptional. Since the first case was reported by Otschkin in 1916, about 30 cases have been described in literature. We report the case of a 43 years-old male patient who had an urgent laparoscopic cholecystectomy with the diagnosis of acute cholecystitis, which pathological study showed the existence of chronic cholecystitis with heterotopic pancreatic tissue in the gallbladder wall.

Inspired from recent insights into the common ground of machine learning, optimization and decision-making, this paper proposes an easy-to-implement, but effective procedure to enhance both the quality of renewable energy forecasts and the competitive edge of renewable energy producers in electricity markets with a dual-price settlement of imbalances. The quality and economic gains brought by the proposed procedure essentially stem from the utilization of valuable predictors (also known as features) in a data-driven newsvendor model that renders a computationally inexpensive linear program. We illustrate the proposed procedure and numerically assess its benefits on a realistic case study that considers the aggregate wind power production in the Danish DK1 bidding zone as the variable to be predicted and traded. Within this context, our procedure leverages, among others, spatial information in the form of wind power forecasts issued by transmission system operators (TSO) in surrounding bidding zones and publicly available in online platforms. We show that our method is able to improve the quality of the wind power forecast issued by the Danish TSO by several percentage points (when measured in terms of the mean absolute or the root mean square error) and to significantly reduce the balancing costs incurred by the wind power producer.Index Terms-Electricity markets, Renewable energy forecasting and trading, Wind power, Optimization, Machine Learning. NOMENCLATURE A. Sets and Indicest Index of time periods. j Index of features. T Training set. T Test set. B. Parameters E Maximum hourly wind energy production (MWh). λ B t Balancing market price at hour t (e/MWh). λ D t Day-ahead market price at hour t (e/MWh). λ − t Upward regulation price in the balancing market at hour t (e/MWh). λ + t Downward regulation price in the balancing market at hour t (e/MWh). ψ − t Marginal opportunity cost for underproduction at hour t (e/MWh). ψ + t Marginal opportunity cost for overproduction at hour t (e/MWh). E t Actual wind energy produced at hour t (MWh). M. A. Muñoz, J. M. Morales (corresponding author) and S. Pineda are with the research group OASYS at

Mitonafide was the first synthetized compound of a new series of 3-nitronaphthalimides with intercalative properties. A phase I study with a conventional escalation scheme was developed. The schedule of drug administration was a daily x 5 days by short (1 h) intravenous (i.v.) infusion, every 21 days. Thirty evaluable patients were treated at doses from 15.4 mg/m2/d x 5 days to 138.6 mg/m2/d x 5 days. The study was interrupted due to appearance of central nervous system toxicity in 5 patients treated at doses above 118 mg/m2 x 5 days. This toxicity consisted firstly of loss of memory in all patients. It was irreversible and progressed in 3 patients to disorientation and confusion, leading to dementia in one of them. This was considered to be dose-limiting toxicity, and since it appeared to be related to the administration schedule, no further studies with short i.v. infusions of mitonafide are recommended. A phase I study utilizing a more desirable administration schedule over longer periods of time is ongoing in other centers.

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