Scientific progress despite irreproducibility: A seeming paradox

It appears paradoxical that science is producing outstanding new results and theories at a rapid rate at the same time that researchers are identifying serious problems in the practice of science that cause many reports to be irreproducible and invalid. Certainly the practice of science needs to be improved and scientists are now pursuing this goal. However, in this perspective we argue that this seeming paradox is not new, has always been part of the way science works, and likely will remain so. We first introduce the paradox. We then review a wide range of challenges that appear to make scientific success difficult. Next, we describe the factors that make science work-in the past, present, and presumably also in the future. We then suggest that remedies for the present practice of science need to be applied selectively so as not to slow progress, and illustrate with a few examples. We conclude with arguments that communication of science needs to emphasize not just problems but the enormous successes and benefits that science has brought and is now bringing to all elements of modern society.Comment: 3 figure

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

Assessing rotation-invariant feature classification for automated wildebeest population counts

Accurate and on-demand animal population counts are the holy grail for wildlife conservation organizations throughout the world because they enable fast and responsive adaptive management policies. While the collection of image data from camera traps, satellites, and manned or unmanned aircraft has advanced significantly, the detection and identification of animals within images remains a major bottleneck since counting is primarily conducted by dedicated enumerators or citizen scientists. Recent developments in the field of computer vision suggest a potential resolution to this issue through the use of rotation-invariant object descriptors combined with machine learning algorithms. Here we implement an algorithm to detect and count wildebeest from aerial images collected in the Serengeti National Park in 2009 as part of the biennial wildebeest count. We find that the per image error rates are greater than, but comparable to, two separate human counts. For the total count, the algorithm is more accurate than both manual counts, suggesting that human counters have a tendency to systematically over or under count images. While the accuracy of the algorithm is not yet at an acceptable level for fully automatic counts, our results show this method is a promising avenue for further research and we highlight specific areas where future research should focus in order to develop fast and accurate enumeration of aerial count data. If combined with a bespoke image collection protocol, this approach may yield a fully automated wildebeest count in the near future.CJT is supported by a Complex Systems Scholar Award from the James S. McDonnell Foundation. JGCH is supported by a Lord Kelvin Adam Smith Fellowship, funding from the British Ecological Society and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 641918 AfricanBioServices. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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