An integrative computational model for intestinal tissue renewal

Objectives\ud \ud The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and functionality, the epithelium is renewed every few days. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of this renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation.\ud \ud Methods\ud \ud At the subcellular level, deterministic models characterise molecular networks, such as cell-cycle control and Wnt signalling. The output of these models determines the behaviour of each epithelial cell in response to intra-, inter- and extracellular cues. The modular nature of the model enables us to easily modify individual assumptions and analyse their effects on the system as a whole.\ud \ud Results\ud \ud We perform virtual microdissection and labelling-index experiments, evaluate the impact of various model extensions, obtain new insight into clonal expansion in the crypt, and compare our predictions with recent mitochondrial DNA mutation data. \ud \ud Conclusions\ud \ud We demonstrate that relaxing the assumption that stem-cell positions are fixed enables clonal expansion and niche succession to occur. We also predict that the presence of extracellular factors near the base of the crypt alone suffices to explain the observed spatial variation in nuclear beta-catenin levels along the crypt axis

The Recognizability and Localizability of Auditory Alarms: Setting Global Medical Device Standards.

Objective Four sets of eight audible alarms matching the functions specified in IEC 60601-1-8 were designed using known principles from auditory cognition with the intention that they would be more recognizable and localizable than those currently specified in the standard. Background The audible alarms associated with IEC 60601-1-8, a global medical device standard, are known to be difficult to learn and retain, and there have been many calls to update them. There are known principles of design and cognition that might form the basis of more readily recognizable alarms. There is also scope for improvement in the localizability of the existing alarms. Method Four alternative sets of alarms matched to the functions specified in IEC 60601-1-8 were tested for recognizability and localizability and compared with the alarms currently specified in the standard. Results With a single exception, all prototype sets of alarms outperformed the current IEC set on both recognizability and localizability. Within the prototype sets, auditory icons were the most easily recognized, but the other sets, using word rhythms and simple acoustic metaphors, were also more easily recognized than the current alarms. With the exception of one set, all prototype sets were also easier to localize. Conclusion Known auditory cognition and perception principles were successfully applied to an existing audible alarm problem. Application This work constitutes the first (benchmarking) phase of replacing the alarms currently specified in the standard. The design principles used for each set demonstrate the relative ease with which different alarm types can be recognized and localized

Validation of digital pathology imaging for primary histopathological diagnosis

Aims: Digital pathology (DP) offers advantages over glass slide microscopy (GS), but data demonstrating a statistically valid equivalent (i.e. non-inferior) performance of DP against GS are required to permit its use in diagnosis. The aim of this study is to provide evidence of non-inferiority. Methods and results: Seventeen pathologists re-reported 3017 cases by DP. Of these, 1009 were re-reported by the same pathologist, and 2008 by a different pathologist. Re-examination of 10 138 scanned slides (2.22 terabytes) produced 72 variances between GS and DP reports, including 21 clinically significant variances. Ground truth lay with GS in 12 cases and with DP in nine cases. These results are within the 95% confidence interval for existing intraobserver and interobserver variability, proving that DP is non-inferior to GS. In three cases, the digital platform was deemed to be responsible for the variance, including a gastric biopsy, where Helicobacter pylori only became visible on slides scanned at the ×60 setting, and a bronchial biopsy and penile biopsy, where dysplasia was reported on DP but was not present on GS. Conclusions: This is one of the largest studies proving that DP is equivalent to GS for the diagnosis of histopathology specimens. Error rates are similar in both platforms, although some problems e.g. detection of bacteria, are predictable

Designing informative warning signals: Effects of indicator type, modality, and task demand on recognition speed and accuracy

An experiment investigated the assumption that natural indicators which exploit existing learned associations between a signal and an event make more effective warnings than previously unlearned symbolic indicators. Signal modality (visual, auditory) and task demand (low, high) were also manipulated. Warning effectiveness was indexed by accuracy and reaction time (RT) recorded during training and dual task test phases. Thirty-six participants were trained to recognize 4 natural and 4 symbolic indicators, either visual or auditory, paired with critical incidents from an aviation context. As hypothesized, accuracy was greater and RT was faster in response to natural indicators during the training phase. This pattern of responding was upheld in test phase conditions with respect to accuracy but observed in RT only in test phase conditions involving high demand and the auditory modality. Using the experiment as a specific example, we argue for the importance of considering the cognitive contribution of the user (viz., prior learned associations) in the warning design process. Drawing on semiotics and cognitive psychology, we highlight the indexical nature of so-called auditory icons or natural indicators and argue that the cogniser is an indispensable element in the tripartite nature of signification

Transferring Patient Care: Patterns of Synchronous Bidisciplinary Communication Between Physicians and Nurses During Handoffs in a Critical Care Unit

Purpose: The transfer of patient care from one health care worker to another involves communication in high-pressure contexts that are often vulnerable to error. This research project captured current practices for handoffs during the critical care stage of surgical recovery in a hospital setting. The objective was to characterize information flowduring transfer and identify patterns of communication between nurses and physicians. Design and Methods: Observations were used to document communication exchanges. The data were analyzed qualitatively according to the types of information exchanged and verbal behavior types. Findings: Reporting and questions were the most common verbal behaviors, and retrospective medical information was the focus of information exchange. The communication was highly interactive when discussing patient status and future care plans. Nurses proactively asked questions to capture a large proportion of the information they needed. Conclusions: Findings reflect positive and constructive patterns of communication during handoffs in the observed hospital unit