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) (

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.

Simulation Games - A Creative Tool for Capacity Building: Experience from the Learning for Sustainability Approach

Games that simulate complex realities to be dealt with in teams are an effective tool for fostering interactive learning processes. they link different levels of decision-making in the household, community and societal contexts. Negotiation and harmonisation of different perceptions and interests, be it within or between different households, form the basis of a common strategy for sustainable development.

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.

Effects of (un)predictable whole body vibrations on visual performance

Over recent years, it has repeatedly been shown that optimal gaze strategies enhance motor control (e.g., Foulsham, 2015). However, little is known, whether, vice versa, visual performance can be improved by optimized motor control. Consequently, in two studies, we investigated visual performance as a function of motor control strategies and task parameters, respectively. In Experiment 1, 72 participants were tested on visual acuity (Landolt) and contrast sensitivity (Grating), while standing in two different postures (upright vs. squat) on a ZEPTOR-platform that vibrated at four different frequencies (0, 4, 8, 12 Hz). After each test, perceived exertion (Borg) was assessed. Significant interactions were revealed for both tests, Landolt: F(3,213)=13.25, p<.01, ηp2=.16, Grating: F(3,213)=4.27, p<.01, ηp2=.06, elucidating a larger loss of acuity/contrast sensitivity with increasing frequencies for the upright compared with the squat posture. For perceived exertion, however, a diametrical interaction for frequency was found for acuity, F(3,213)=7.45, p<.01, ηp2=.09, and contrast sensitivity, F(3,213)=7.08, p < .01, ηp2=.09, substantiating that the impaired visual performance cannot be attributed to exertion. Consequently, the squat posture could permit better head and, hence, gaze stabilization. In Experiment 2, 64 participants performed the same tests while standing in a squat position on a ski-simulator, which vibrated with two different frequencies (2.4, 3.6 Hz) and amplitudes (50, 100 mm) in a predictable or unpredictable manner. Control strategies were identified by tracking segmental motion, which allows to derive damping characteristics. Considerable main effects were found for frequency, all F’s(1,52)>10.31, all p’s<.01, all ηp2’s>.16, as well as, in the acuity test, for predictability, F(1,52)=10.31, p<.01, ηp2=.17, and by tendency for amplitude, F(1,52)=3.53, p=.06, ηp2=.06. A significant correlation between the damping amplitude in the knee joint and the performance drop in visual acuity, r=-.97, p<.001, again points towards the importance of motor control strategies to maintain optimal visual performance.

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.

Combining qualitative and quantitative methods to analyze serious games outcomes: A pilot study for a new cognitive screening tool

Computer games for a serious purpose - so called serious games can provide additional information for the screening and diagnosis of cognitive impairment. Moreover, they have the advantage of being an ecological tool by involving daily living tasks. However, there is a need for better comprehensive designs regarding the acceptance of this technology, as the target population is older adults that are not used to interact with novel technologies. Moreover given the complexity of the diagnosis and the need for precise assessment, an evaluation of the best approach to analyze the performance data is required. The present study examines the usability of a new screening tool and proposes several new outlines for data analysis.