Survey of the quality of experimental design, statistical analysis and reporting of research using animals

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria

Testing A (Stringy) Model of Quantum Gravity

I discuss a specific model of space-time foam, inspired by the modern non-perturbative approach to string theory (D-branes). The model views our world as a three brane, intersecting with D-particles that represent stringy quantum gravity effects, which can be real or virtual. In this picture, matter is represented generically by (closed or open) strings on the D3 brane propagating in such a background. Scattering of the (matter) strings off the D-particles causes recoil of the latter, which in turn results in a distortion of the surrounding space-time fluid and the formation of (microscopic, i.e. Planckian size) horizons around the defects. As a mean-field result, the dispersion relation of the various particle excitations is modified, leading to non-trivial optical properties of the space time, for instance a non-trivial refractive index for the case of photons or other massless probes. Such models make falsifiable predictions, that may be tested experimentally in the foreseeable future. I describe a few such tests, ranging from observations of light from distant gamma-ray-bursters and ultra high energy cosmic rays, to tests using gravity-wave interferometric devices and terrestrial particle physics experients involving, for instance, neutral kaons.Comment: 25 pages LATEX, four figures incorporated, uses special proceedings style. Invited talk at the third international conference on Dark Matter in Astro and Particle Physics, DARK2000, Heidelberg, Germany, July 10-15 200

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest

Conformal Quivers and Melting Molecules

Quiver quantum mechanics describes the low energy dynamics of a system of wrapped D-branes. It captures several aspects of single and multicentered BPS black hole geometries in four-dimensional $\mathcal{N} = 2$ supergravity such as the presence of bound states and an exponential growth of microstates. The Coulomb branch of an Abelian three node quiver is obtained by integrating out the massive strings connecting the D-particles. It allows for a scaling regime corresponding to a deep AdS$_2$ throat on the gravity side. In this scaling regime, the Coulomb branch is shown to be an $SL(2,\mathbb{R})$ invariant multi-particle superconformal quantum mechanics. Finally, we integrate out the strings at finite temperature---rather than in their ground state---and show how the Coulomb branch `melts' into the Higgs branch at high enough temperatures. For scaling solutions the melting occurs for arbitrarily small temperatures, whereas bound states can be metastable and thus long lived. Throughout the paper, we discuss how far the analogy between the quiver model and the gravity picture, particularly within the AdS$_2$ throat, can be taken.Comment: 49 pages, 16 figure

The Elite-Plus stem migrates more than the flanged Charnley stem: A clinical, radiographic, and radiostereometric analysis of 114 patients with an average of 7 years follow-up

Background and purpose The Charnley Elite-Plus stem was introduced in 1993 as a presumed improvement of the flanged Charnley stem. We started this study in 1996 to investigate the migratory pattern of the Elite-Plus stem. Patients and methods We followed 114 patients with osteoarthritis and a primary total hip replacement with the Elite-Plus stem. Mean age at the time of operation was 64 (50-76) years. The mean follow-up time was 6.5 (2-7) years. Radiographs were evaluated with respect to cementing technique, migration, and wear measured by radiostereometry (RSA). Results The stem survival was 98% (CI: 96-100) at 7 years and 92% (CI: 86-97) at 10 years. Mean migration of the femoral head was 0.35 mm (SD 0.3) medially, 0.51 mm (SD 0.6) distally, and 1.1 mm (SD 1.8) in the dorsal direction. Mean total point motion was 1.7 mm (SD 1.7). The migration of the stems stabilized after 5 years in the medial and dorsal directions, but continued to subside slightly. Migration along any of the axes was higher if the cementing technique was inferior. Interpretation Patients with a Charnley Elite-Plus stem and defects in the cement mantle or other signs of inferior implantation technique should be carefully monitored

Lorentz violation naturalness revisited

We revisit here the naturalness problem of Lorentz invariance violations on a simple toy model of a scalar field coupled to a fermion field via a Yukawa interaction. We first review some well-known results concerning the low-energy percolation of Lorentz violation from high energies, presenting some details of the analysis not explicitly discussed in the literature and discussing some previously unnoticed subtleties. We then show how a separation between the scale of validity of the effective field theory and that one of Lorentz invariance violations can hinder this low-energy percolation. While such protection mechanism was previously considered in the literature, we provide here a simple illustration of how it works and of its general features. Finally, we consider a case in which dissipation is present, showing that the dissipative behaviour does not percolate generically to lower mass dimension operators albeit dispersion does. Moreover, we show that a scale separation can protect from unsuppressed low-energy percolation also in this case. \ua9 2016, The Author(s)

Does Presentation Format Influence Visual Size Discrimination in Tufted Capuchin Monkeys (Sapajus spp.)?

Most experimental paradigms to study visual cognition in humans and non-human species are based on discrimination tasks involving the choice between two or more visual stimuli. To this end, different types of stimuli and procedures for stimuli presentation are used, which highlights the necessity to compare data obtained with different methods. The present study assessed whether, and to what extent, capuchin monkeys\u27 ability to solve a size discrimination problem is influenced by the type of procedure used to present the problem. Capuchins\u27 ability to generalise knowledge across different tasks was also evaluated. We trained eight adult tufted capuchin monkeys to select the larger of two stimuli of the same shape and different sizes by using pairs of food items (Experiment 1), computer images (Experiment 1) and objects (Experiment 2). Our results indicated that monkeys achieved the learning criterion faster with food stimuli compared to both images and objects. They also required consistently fewer trials with objects than with images. Moreover, female capuchins had higher levels of acquisition accuracy with food stimuli than with images. Finally, capuchins did not immediately transfer the solution of the problem acquired in one task condition to the other conditions. Overall, these findings suggest that - even in relatively simple visual discrimination problems where a single perceptual dimension (i.e., size) has to be judged - learning speed strongly depends on the mode of presentation

Longitudinal multi-centre brain imaging studies: guidelines and practical tips for accurate and reproducible imaging endpoints and data sharing

Abstract Background Research involving brain imaging is important for understanding common brain diseases. Study endpoints can include features and measures derived from imaging modalities, providing a benchmark against which other phenotypical data can be assessed. In trials, imaging data provide objective evidence of beneficial and adverse outcomes. Multi-centre studies increase generalisability and statistical power. However, there is a lack of practical guidelines for the set-up and conduct of large neuroimaging studies. Methods We address this deficit by describing aspects of study design and other essential practical considerations that will help researchers avoid common pitfalls and data loss. Results The recommendations are grouped into seven categories: (1) planning, (2) defining the imaging endpoints, developing an imaging manual and managing the workflow, (3) performing a dummy run and testing the analysis methods, (4) acquiring the scans, (5) anonymising and transferring the data, (6) monitoring quality, and (7) using structured data and sharing data. Conclusions Implementing these steps will lead to valuable and usable data and help to avoid imaging data wastage

Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m−2 of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1–3, 8–10, 15–17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1–9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44–72) and median duration of PSA response was 8.0 months (95% CI: 6.9–9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel