A Simple Model for Pulse Profiles from Precessing Pulsars, with Special Application to Relativistic Binary PSR B1913+16

We study the observable pulse profiles that can be generated from precessing pulsars. A novel coordinate system is defined to aid visualization of the observing geometry. Using this system we explore the different families of profiles that can be generated by simple, circularly symmetric beam shapes. An attempt is then made to fit our model to the observations of relativistic binary PSR B1913+16. It is found that while qualitatively similar pulse profiles can be produced, this minimal model is insufficient for an accurate match to the observational data. Consequently, we confirm that the emission beam of PSR B1913+16 must deviate from circular symmetry, as first reported by Weisberg and Taylor. However, the approximate fits obtained suggest that it may be sufficient to consider only minimal deviations from a circular beam in order to explain the data. We also comment on the applicability of our analysis technique to other precessing pulsars, both binary and isolated.Comment: 35 pages and 8 figures. Published versio

Activity of raltitrexed and gemcitabine in advanced pancreatic cancer

Background: Gemcitabine has evolved as standard therapy in advanced pancreatic cancer since the demonstration of a significant clinical benefit. Phase II trials have shown that gemcitabine can be successfully combined with thymidylate synthase (TS) inhibitors such as continuous-infusion 5-fluorouracil (5-FU). However, continuous-infusion 5-FU is inconvenient because of the need for a central venous access. The aim of this study was to assess the efficacy and safety of gemcitabine in combination with raltitrexed (Tomudex), a novel and selective TS inhibitor that has the advantage of a 3-weekly treatment interval and manageable toxicity. Patients and methods: Chemotherapy-naïve patients with measurable advanced pancreatic cancer were treated with raltitrexed 3 mg/m2 as a 15-min infusion on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days. Results: Twenty-five eligible patients (17 male, eight female) with metastatic (21 patients) or locally advanced (four patients) disease entered the study. The median number of courses per patient was four (range 1-14). One patient was not evaluable for response. There were three partial remissions [12%; 95% confidence interval (CI) 2.6% to 31.2%] and nine stable disease situations (36%; 95% CI 18.0% to 57.5%), while the tumours of 12 patients (48%; 95% CI 27.8% to 68.7%) showed progressive disease after three treatment cycles. WHO grade 3/4 toxicity was rare and symptomatic in only one patient, who experienced grade 4 diarrhoea and grade 3 nausea and vomiting. Symptomatic benefit was seen in 12 patients. Median survival was 185 days (95% CI 129-241) with six patients still alive. Conclusions: The efficacy of raltitrexed plus gemcitabine is limited, but compares well with other chemotherapy treatment options in advanced pancreatic cancer. However, this combination is convenient and symptomatic toxicity is rare. Thus, raltitrexed and gemcitabine should be investigated further in combination with drugs interfering with specific molecular target

A randomized crossover trial assessing patient preference for two different types of portable infusion-pump devices

Background: A variety of anticancer agents are better tolerated and more effective if given as continuous compared to bolus administration. Portable pump devices are needed to allow outpatient continuous infusion. Different types of portable pumps are available and we tested patient preference in a randomized crossover design. Patients and methods: Patients on continuous infusion fluorouracil were randomly assigned to start treatment with an elastomeric infusor (Baxter) or a mechanical, electronically controlled pump (CADD-1™, Pharmacia) and crossed over to the alternative model after three weeks. After exposure to both pump types patients were asked to indicate their preferred device. Results: After 10 patients the study was closed because all study participants preferred the elastomeric pump (P < 0.01). Reasons were pump weight (100%), smaller pump size (89%), interference with daily activities (89%), user friendliness (56%), impact on sleep (44%), and lack of technical problems (22%). Although the mechanical pump required more handling time for the first two refillings, the learning curve suggested about equal time requirement thereafter. Conclusion: In the interest of patient comfort, the disposable elastomeric infusor is an acceptable alternative to the more accurate electronically controlled pumps especially for drugs with a short half-life and a favorable toxicity profil

The global cropland footprint of the non-food bioeconomy

A rapidly growing share of global agricultural areas is devoted to the production of biomass for non-food purposes. The derived products include, for example, biofuels, textiles, detergents or cosmetics. Given the far-reaching global implications of an expanding non-food bioeconomy, an assessment of the bioeconomy’s resource use from a footprint perspective is urgently needed. We determine the global cropland footprint of non-food products with a hybrid land flow accounting model combining data from the Food and Agriculture Organization and the multi-regional input-output model EXIOBASE. The globally interlinked model covers all cropland areas used for the production of crop- and animal-based non-food commodities for the years from 1995 to 2010. We analyse global patterns of raw material producers, processers and consumers of bio-based non-food products, with a particular focus on the European Union. Results illustrate that the EU is a major processer and the number one consumer region of non-food cropland, despite being only the fifth largest producing region. Two thirds of the cropland required to satisfy EU non-food consumption are located in other world regions, giving rise to a significant dependency on imported products and to potential impacts on distant ecosystems. With almost 29% in 2010, oilseed production, used to produce, for example, biofuels, detergents and polymers, represents the dominant share in the EU’s non-food cropland footprint. There is also a significant contribution of more traditional non-food biomass uses such as fibre crops (for textiles) and animal hides and skins (for leather products). Our study emphasises the importance of comprehensively assessing the implications of the non-food bioeconomy expansion as envisaged in various policy strategies, such as the Bioeconomy Strategy of the European Commission

Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation

Background: Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with ‘good-risk' characteristics of disease were randomized. ‘Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each ≤3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization. Results: The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%. Conclusions: These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantag

Microscale Analysis of Spacecraft Heat Shields

Imagine entering Earths atmosphere after returning from the outer solar system. A heat shield less than 2 inches thick protects you from temperatures up to 2,900 Celsius (5,252 Fahrenheit). Such conditions were experienced by NASAs Stardust capsule during reentry in 2006. The only materials capable of providing the necessary protection are composites with complex microstructures. Evaluating these materials is difficult, requiring precise knowledge of their properties. To this end, NASA scientists are developing research codes to compute material properties and simulate ablation at the microscale using agency supercomputers. Utilizing these tools, along with experiments, researchers are working to push the limits of spaceflight, allowing for greater flexibility in future space missions