Feasibility platform for stroke studies: an online tool to improve eligibility criteria for clinical trials

BACKGROUND AND PURPOSE Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. METHODS We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. RESULTS Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de, displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. CONCLUSIONS FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.

Factors Associated with Bone Level Alterations at Implants with Inner-Cone Connection and Platform Switching

Purpose.This retrospective cohort study evaluated factors for peri-implant bone level changes (ΔIBL) associated with an implant type with inner-cone implant-abutment connection, rough neck surface, and platform switching (AT). Materials and Methods. All AT placed at the Department of Prosthodontics of the University of Bern between January 2004 and December 2005 were included in this study. All implants were examined by single radiographs using the parallel technique taken at surgery (T0) and obtained at least 6 months after surgery (T1). Possible influencing factors were analysed first using t-test (normal distribution) or the nonparametric Wilcoxon test (not normal distribution), and then a mixed model q variance analysis was performed. Results. 43 patients were treated with 109 implants. Five implants in 2 patients failed (survival rate: 95.4%).Mean ΔIBL in group 1 (T1: 6–12 months after surgery) was −0.65 ± 0.82mm and −0.69 ± 0.82mm in group 2 (T1: >12 months after surgery) (

School-age children show a bias toward fantasy classifications after playing a platform game

We investigated the influence of playing a video game on children’s ability to distinguish between fantasy and reality. School-age children played a platform game for 15 min and then performed a fantasy/reality distinction task in which they were to judge whether images (from the platform game and from other games) were fantasy images or reality images. Unlike those in the control group (who played a memory game), the children in the experimental group showed a response bias toward mistakenly classifying reality images from the video game as fantasy images (as determined by means of an analysis based on signal detection theory). We conclude that playing the video game exerted a short-term influence on children’s ability to distinguish between fantasy and reality.

MorphoGraphX: A platform for quantifying morphogenesis in 4D

Morphogenesis emerges from complex multiscale interactions between genetic and mechanical processes. To understand these processes, the evolution of cell shape, proliferation and gene expression must be quantified. This quantification is usually performed either in full 3D, which is computationally expensive and technically challenging, or on 2D planar projections, which introduces geometrical artifacts on highly curved organs. Here we present MorphoGraphX (www.MorphoGraphX.org), a software that bridges this gap by working directly with curved surface images extracted from 3D data. In addition to traditional 3D image analysis, we have developed algorithms to operate on curved surfaces, such as cell segmentation, lineage tracking and fluorescence signal quantification. The software’s modular design makes it easy to include existing libraries, or to implement new algorithms. Cell geometries extracted with MorphoGraphX can be exported and used as templates for simulation models, providing a powerful platform to investigate the interactions between shape, genes and growth.DOI: http://dx.doi.org/10.7554/eLife.05864.001Author keywordsResearch organism

Towards personalized medicine: Chemosensitivity assays of patient lung cancer cell spheroids in a perfused microfluidic platform

Cancer is responsible for millions of deaths worldwide and the variability in disease patterns calls for patient-specific treatment. Therefore, personalized treatment is expected to become a daily routine in prospective clinical tests. In addition to genetic mutation analysis, predictive chemosensitive assays using patient's cells will be carried out as a decision making tool. However, prior to their widespread application in clinics, several challenges linked to the establishment of such assays need to be addressed. To best predict the drug response in a patient, the cellular environment needs to resemble that of the tumor. Furthermore, the formation of homogeneous replicates from a scarce amount of patient's cells is essential to compare the responses under various conditions (compound and concentration). Here, we present a microfluidic device for homogeneous spheroid formation in eight replicates in a perfused microenvironment. Spheroid replicates from either a cell line or primary cells from adenocarcinoma patients were successfully created. To further mimic the tumor microenvironment, spheroid co-culture of primary lung cancer epithelial cells and primary pericytes were tested. A higher chemoresistance in primary co-culture spheroids compared to primary monoculture spheroids was found when both were constantly perfused with cisplatin. This result is thought to be due to the barrier created by the pericytes around the tumor spheroids. Thus, this device can be used for additional chemosensitivity assays (e.g. sequential treatment) of patient material to further approach the personalized oncology field.

The Martian Gas-Analytic Package for the Landing Platform Experiments of the ExoMars 2018

The paper describes the architecture of the Martian Gas Analytic Package, which is proposed for the Russian ExoMars Lander 2018.

Upper Ewaso Ngiro River Basin Water Management Information Platform: Survey on Development priorities, Information Needs and Conflict Management Efforts

A survey of development priorities and needs for water related information, including information on Water User Associations

Software Development in the Cloud: Exploring the Affordances of Platform-as-a-Service

Software development teams increasingly adopt platform-as-a-service (PaaS), i.e., cloud services that make software development infrastructure available over the internet. Yet, empirical evidence of whether and how software development work changes with the use of PaaS is difficult to find. We performed a grounded-theory study to explore the affordances of PaaS for software development teams. We find that PaaS enables software development teams to enforce uniformity, to exploit knowledge embedded in technology, to enhance agility, and to enrich jobs. These affordances do not arise in a vacuum. Their emergence is closely interwoven with changes in methodologies, roles, and norms that give rise to self-organizing, loosely coupled teams. Our study provides rich descriptions of PaaS-based software development and an emerging theory of affordances of PaaS for software development teams.

Coordinating Platform-Based Multi-Sourcing: Introducing the Theory of Convention

Spurred by the consumer market, companies increasingly deploy smartphones or tablet computers in their operations. However, unlike private users, companies typically struggle to cover their needs with existing applications, and therefore expand mobile software platforms through customized applications from multiple software vendors. Companies thereby combine the concepts of multi-sourcing and software platform ecosystems in a novel platform-based multi-sourcing setting. This implies, however, the clash of two different approaches towards the coordination of the underlying one-to-many inter-organizational relationships. So far, however, little is known about impacts of merging coordination approaches. Relying on convention theory, we addresses this gap by analyzing a platform-based multi-sourcing project between a client and six software vendors, that develop twenty-three custom-made applications on a common platform (Android). In doing so, we aim to understand how unequal coordination approaches merge, and whether and for what reason particular coordination mechanisms, design decisions, or practices disappear, while new ones emerge.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Loss on ignition as a method for estimating organic and carbonate content in sediments: reproducibility and comparability of results

Five test runs were performed to assess possible bias when performing the loss on ignition (LOI) method to estimate organic matter and carbonate content of lake sediments. An accurate and stable weight loss was achieved after 2 h of burning pure CaCO3 at 950 °C, whereas LOI of pure graphite at 530 °C showed a direct relation to sample size and exposure time, with only 40-70% of the possible weight loss reached after 2 h of exposure and smaller samples losing weight faster than larger ones. Experiments with a standardised lake sediment revealed a strong initial weight loss at 550 °C, but samples continued to lose weight at a slow rate at exposure of up to 64 h, which was likely the effect of loss of volatile salts, structural water of clay minerals or metal oxides, or of inorganic carbon after the initial burning of organic matter. A further test-run revealed that at 550 °C samples in the centre of the furnace lost more weight than marginal samples. At 950 °C this pattern was still apparent but the differences became negligible. Again, LOI was dependent on sample size. An analytical LOI quality control experiment including ten different laboratories was carried out using each laboratory's own LOI procedure as well as a standardised LOI procedure to analyse three different sediments. The range of LOI values between laboratories measured at 550 °C was generally larger when each laboratory used its own method than when using the standard method. This was similar for 950 °C, although the range of values tended to be smaller. The within-laboratory range of LOI measurements for a given sediment was generally small. Comparisons of the results of the individual and the standardised method suggest that there is a laboratory-specific pattern in the results, probably due to differences in laboratory equipment and/or handling that could not be eliminated by standardising the LOI procedure. Factors such as sample size, exposure time, position of samples in the furnace and the laboratory measuring affected LOI results, with LOI at 550 °C being more susceptible to these factors than LOI at 950 °C. We, therefore, recommend analysts to be consistent in the LOI method used in relation to the ignition temperatures, exposure times, and the sample size and to include information on these three parameters when referring to the method.

Peri-implant bone loss of dental implants with platform-switching design after 5 years of loading: a cross-sectional study

OBJECTIVE The aim of this cross-sectional study was to estimate bone loss of implants with platform-switching design and analyze possible risk indicators after 5 years of loading in a multi-centered private practice network. METHOD AND MATERIALS Peri-implant bone loss was measured radiographically as the distance from the implant shoulder to the mesial and distal alveolar crest, respectively. Risk factor analysis for marginal bone loss included type of implant prosthetic treatment concept and dental status of the opposite arch. RESULTS A total of 316 implants in 98 study patients after 5 years of loading were examined. The overall mean value for radiographic bone loss was 1.02 mm (SD ± 1.25 mm, 95% CI 0.90- 1.14). Correlation analyses indicated a strong association of peri-implant bone loss > 2 mm for removable implant-retained prostheses with an odds ratio of 53.8. CONCLUSION The 5-year-results of the study show clinically acceptable values of mean bone loss after 5 years of loading. Implant-supported removable prostheses seem to be a strong co-factor for extensive bone level changes compared to fixed reconstructions. However, these results have to be considered for evaluation of the included special cohort under private dental office conditions.

Salinity of the Eocene Arctic Ocean from oxygen isotope analysis of fish bone carbonate

Stable isotope analysis was performed on the structural carbonate of fish bone apatite from early and early middle Eocene samples (~55 to ~45 Ma) recently recovered from the Lomonosov Ridge by Integrated Ocean Drilling Program Expedition 302 (the Arctic Coring Expedition). The d18O values of the Eocene samples ranged from -6.84 per mil to -2.96 per mil Vienna Peedee belemnite, with a mean value of -4.89 per mil, compared to 2.77 per mil for a Miocene sample in the overlying section. An average salinity of 21 to 25 per mil was calculated for the Eocene Arctic, compared to 35 per mil for the Miocene, with lower salinities during the Paleocene Eocene thermal maximum, the Azolla event at ~48.7 Ma, and a third previously unidentified event at ~47.6 Ma. At the Azolla event, where the organic carbon content of the sediment reaches a maximum, a positive d13C excursion was observed, indicating unusually high productivity in the surface waters.