A 2.75-Approximation Algorithm for the Unconstrained Traveling Tournament Problem

A 2.75-approximation algorithm is proposed for the unconstrained traveling tournament problem, which is a variant of the traveling tournament problem. For the unconstrained traveling tournament problem, this is the first proposal of an approximation algorithm with a constant approximation ratio. In addition, the proposed algorithm yields a solution that meets both the no-repeater and mirrored constraints. Computational experiments show that the algorithm generates solutions of good quality.Comment: 12 pages, 1 figur

Bleeding Meckel’s diverticulum in a 4-month-old infant: Treatment with laparoscopic diverticulectomy. A case report and review of the literature

A bleeding Meckel’s diverticulum is presented in a 4-month-old African American infant. This event is rare at this age, and our patient is only the second 4-month-old infant reported in the English literature. The infant presented with painless frank rectal bleeding, the blood being maroon-colored, and clots were found in the diaper. There was also anemia, with an hemoglobin of less than 8 gm/dl. The color of the blood suggested a bleeding site in the ileo-cecal region, a Meckel’s diverticulum was suspected, which was then confirmed by an isotope scan. A typical Meckel’s diverticulum was found on laparoscopic surgery, was excised, and the infant made an uneventful recovery

The european flood alert system EFAS – Part 2: Statistical skill assessment of probabilistic and deterministic operational forecasts

Since 2005 the European Flood Alert System (EFAS) has been producing probabilistic hydrological forecasts in pre-operational mode at the Joint Research Centre (JRC) of the European Commission. EFAS aims at increasing preparedness for floods in trans-national European river basins by providing medium-range deterministic and probabilistic flood forecasting information, from 3 to 10 days in advance, to national hydro-meteorological services. <br><br> This paper is Part 2 of a study presenting the development and skill assessment of EFAS. In Part 1, the scientific approach adopted in the development of the system has been presented, as well as its basic principles and forecast products. In the present article, two years of existing operational EFAS forecasts are statistically assessed and the skill of EFAS forecasts is analysed with several skill scores. The analysis is based on the comparison of threshold exceedances between proxy-observed and forecasted discharges. Skill is assessed both with and without taking into account the persistence of the forecasted signal during consecutive forecasts. <br><br> Skill assessment approaches are mostly adopted from meteorology and the analysis also compares probabilistic and deterministic aspects of EFAS. Furthermore, the utility of different skill scores is discussed and their strengths and shortcomings illustrated. The analysis shows the benefit of incorporating past forecasts in the probability analysis, for medium-range forecasts, which effectively increases the skill of the forecasts

Эволюция информационных технологий и их роль в развитии экономики и общества

In Russia there is a problem of formation of information economy is one of the most pressing problems of our time. The information economy is needed for further stable development of the country and the subsequent introduction of Russia into the global economy

Flemish Normative Data for the Buschke Selective Reminding Test

The purpose of this study was to provide normative data for a Flemish version of the Buschke Selective Reminding Test (SRT). The SRT allows for the simultaneous analysis of several components of verbal memory, such as short and long term retrieval. The Flemish SRT was administered to 3257 neurologically healthy adults (1627 men and 1630 women, age range = 18–94 years). Effects of age, sex and education on SRT performance were assessed. Results indicate that SRT performance decreased with age and that this decline accelerated in men compared to women. Furthermore, an effect of education was found favoring participants who completed a higher education. Normative data quantified through percentile ranks and stratified by age, sex and education level are provided

T Cells Contain an RNase-Insensitive Inhibitor of APOBEC3G Deaminase Activity

The deoxycytidine deaminase APOBEC3G (A3G) is expressed in human T cells and inhibits HIV-1 replication. When transfected into A3G-deficient epithelial cell lines, A3G induces catastrophic hypermutation by deaminating the HIV-1 genome. Interestingly, studies suggest that endogenous A3G in T cells induces less hypermutation than would be expected. However, to date, the specific deaminase activity of endogenous A3G in human CD4+ T cells has not been examined directly. Here, we compared deaminase activity of endogenous and exogenous A3G in various human cell lines using a standard assay and a novel, quantitative, high-throughput assay. Exogenous A3G in epithelial cell lysates displayed deaminase activity only following RNase treatment, as expected given that A3G is known to form an enzymatically inactive RNA-containing complex. Surprisingly, comparable amounts of endogenous A3G from T cell lines or from resting or activated primary CD4+ T cells exhibited minimal deaminase activity, despite RNase treatment. Specific deaminase activity of endogenous A3G in H9, CEM, and other T cell lines was up to 36-fold lower than specific activity of exogenous A3G in epithelial-derived cell lines. Furthermore, RNase-treated T cell lysates conferred a dose-dependent inhibition to epithelial cell lysates expressing enzymatically active A3G. These studies suggest that T cells, unlike epithelial-derived cell lines, express an unidentified RNase-resistant factor that inhibits A3G deaminase activity. This factor could be responsible for reduced levels of hypermutation in T cells, and its identification and blockade could offer a means for increasing antiretroviral intrinsic immunity of T cells

Applying a cost-based pricing model for innovative cancer treatments subject to indication expansion:A case study for pembrolizumab and daratumumab

BACKGROUND: Expanding the indication of already approved immuno-oncology drugs presents treatment opportunities for patients but also strains healthcare systems. Cost-based pricing models are discussed as a possibility for cost containment. This study focuses on two drugs, pembrolizumab (Keytruda) and daratumumab (Darzalex), to explore the potential effect of indication broadening on the estimated price when using the cost-based pricing (CBP) model proposed by Uyl-de Groot and Löwenberg (2018). METHODS: The model was used to calculate cumulative yearly prices, cumulative prices per indication, and non-cumulative indication-based prices using inputs such as research and development (R&amp;D) costs, manufacturing costs, eligible patient population, and a profit margin. A deterministic stepwise analysis and scenario analysis were conducted to examine how sensitive the estimated price is to the different input assumptions. RESULTS: The yearly cumulative cost-based prices (CBPs) ranged from €52 to €885 for pembrolizumab per vial and €823 to €31,941 for daratumumab per vial. Prices were higher in initial years or indications due to smaller patient populations, decreased over time or after additional indications. Sensitivity analysis showed that the number of eligible patients had the most significant impact on the estimated price. In the scenario analysis the profit margin contributed most to a higher CBPs for both drugs. Lower estimates resulted from assumed lower R&amp;D costs. DISCUSSION: The estimated CBPs are consistently lower than Dutch list prices for pembrolizumab (€2,861), mainly resulting from larger patient populations in registered indications. However, daratumumab's list prices fall within the range of modeled CBPs depending on the year or indication (€4,766). Both CBPs decrease over time or with additional indications. The number of eligible patients and initial R&amp;D costs have the most significant influence on the CBPs. These findings contribute to the ongoing discussions on pharmaceutical pricing, especially concerning cancer drugs with expanding indications.</p