An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Mechanisms and evolution of plant resistance to aphids

Aphids are important herbivores of both wild and cultivated plants. Plants rely on unique mechanisms of recognition, signalling and defence to cope with the specialized mode of phloem feeding by aphids. Aspects of the molecular mechanisms underlying aphid-plant interactions are beginning to be understood. Recent advances include the identification of aphid salivary proteins involved in host plant manipulation, and plant receptors involved in aphid recognition. However, a complete picture of aphid-plant interactions requires consideration of the ecological outcome of these mechanisms in nature, and the evolutionary processes that shaped them. Here we identify general patterns of resistance, with a special focus on recognition, phytohormonal signalling, secondary metabolites and induction of plant resistance. We discuss how host specialization can enable aphids to co-opt both the phytohormonal responses and defensive compounds of plants for their own benefit at a local scale. In response, systemically induced resistance in plants is common and often involves targeted responses to specific aphid species or even genotypes. As co-evolutionary adaptation between plants and aphids is ongoing, the stealthy nature of aphid feeding makes both the mechanisms and outcomes of these interactions highly distinct from those of other herbivore-plant interactions. © 2016 Macmillan Publishers Limited.

Cement distribution, volume, and compliance in vertebroplasty: some answers from an anatomy-based nonlinear finite element study

STUDY DESIGN: The biomechanics of vertebral bodies augmented with real distributions of cement were investigated using nonlinear finite element (FE) analysis. OBJECTIVES: To compare stiffness, strength, and stress transfer of augmented versus nonaugmented osteoporotic vertebral bodies under compressive loading. Specifically, to examine how cement distribution, volume, and compliance affect these biomechanical variables. SUMMARY OF BACKGROUND DATA: Previous FE studies suggested that vertebroplasty might alter vertebral stress transfer, leading to adjacent vertebral failure. However, no FE study so far accounted for real cement distributions and bone damage accumulation. METHODS: Twelve vertebral bodies scanned with high-resolution pQCT and tested in compression were augmented with various volumes of cements and scanned again. Nonaugmented and augmented pQCT datasets were converted to FE models, with bone properties modeled with an elastic, plastic and damage constitutive law that was previously calibrated for the nonaugmented models. The cement-bone composite was modeled with a rule of mixture. The nonaugmented and augmented FE models were subjected to compression and their stiffness, strength, and stress map calculated for different cement compliances. RESULTS: Cement distribution dominated the stiffening and strengthening effects of augmentation. Models with cement connecting either the superior or inferior endplate (S/I fillings) were only up to 2 times stiffer than the nonaugmented models with minimal strengthening, whereas those with cement connecting both endplates (S + I fillings) were 1 to 8 times stiffer and 1 to 12 times stronger. Stress increases above and below the cement, which was higher for the S + I cases and was significantly reduced by increasing cement compliance. CONCLUSION: The developed FE approach, which accounts for real cement distributions and bone damage accumulation, provides a refined insight into the mechanics of augmented vertebral bodies. In particular, augmentation with compliant cement bridging both endplates would reduce stress transfer while providing sufficient strengthening.

Recognition of activities of daily living in healthy subjects using two ad-hoc classifiers

Activities of daily living (ADL) are important for quality of life. They are indicators of cognitive health status and their assessment is a measure of independence in everyday living. ADL are difficult to reliably assess using questionnaires due to self-reporting biases. Various sensor-based (wearable, in-home, intrusive) systems have been proposed to successfully recognize and quantify ADL without relying on self-reporting. New classifiers required to classify sensor data are on the rise. We propose two ad-hoc classifiers that are based only on non-intrusive sensor data. METHODS: A wireless sensor system with ten sensor boxes was installed in the home of ten healthy subjects to collect ambient data over a duration of 20 consecutive days. A handheld protocol device and a paper logbook were also provided to the subjects. Eight ADL were selected for recognition. We developed two ad-hoc ADL classifiers, namely the rule based forward chaining inference engine (RBI) classifier and the circadian activity rhythm (CAR) classifier. The RBI classifier finds facts in data and matches them against the rules. The CAR classifier works within a framework to automatically rate routine activities to detect regular repeating patterns of behavior. For comparison, two state-of-the-art [Naïves Bayes (NB), Random Forest (RF)] classifiers have also been used. All classifiers were validated with the collected data sets for classification and recognition of the eight specific ADL. RESULTS: Out of a total of 1,373 ADL, the RBI classifier correctly determined 1,264, while missing 109 and the CAR determined 1,305 while missing 68 ADL. The RBI and CAR classifier recognized activities with an average sensitivity of 91.27 and 94.36%, respectively, outperforming both RF and NB. CONCLUSIONS: The performance of the classifiers varied significantly and shows that the classifier plays an important role in ADL recognition. Both RBI and CAR classifier performed better than existing state-of-the-art (NB, RF) on all ADL. Of the two ad-hoc classifiers, the CAR classifier was more accurate and is likely to be better suited than the RBI for distinguishing and recognizing complex ADL.