Predicting pilot error on the flight deck: Validation of a new methodology and a multiple methods and analysts approach to enhancing error prediction sensitivity

The Human Error Template (HET) is a recently developed methodology for predicting designed induced pilot error. This article describes a validation study undertaken to compare the performance of HET against three contemporary Human Error Identification (HEI) approaches when used to predict pilot errors for an approach and landing task and also to compare individual analyst error predictions to an approach to enhancing error prediction sensitivity: the multiple analysts and methods approach, whereby multiple analyst predictions using a range of HEI technique are pooled. The findings indicate that, of the four methodologies used in isolation, analysts using the HET methodology offered the most accurate error predictions, and also that the multiple analysts and methods approach was more successful overall in terms of error prediction sensitivity than the three other methods but not the HET approach. The results suggest that when predicting design induced error, it is appropriate to use domain specific approaches and also a toolkit of different HEI approaches and multiple analysts in order to heighten error prediction sensitivity

Corrigendum to “Implementation of tidal turbines in MIKE 3 and Delft3D models of Pentland Firth & Orkney waters” [Ocean Coast. Manag. 147 (2017) 21–36]

© 2017 Elsevier Ltd The authors regret that a software error caused incorrect predictions for the effects of tidal turbines in Delft3D. The predictions without turbines are unaffected, as are those from the MIKE 3 model. The overall conclusions of the article remain valid. Figs. 12–15 as published are incorrect. Replacements for Figs. 12–14 are presented here. Following this correction the differences in the effects of energy extraction between the two models are much smaller. As a result the discussion of these differences in Section 6 should be disregarded, and Fig. 15 is no longer required. The authors would like to apologise for any inconvenience caused. The version of the code for adding turbines to Delft3D that is publicly available has been corrected, and anybody using this for their own work is urged to download the latest version. [Figure presented] Fig. 12: (a) 400 turbines in the Inner Sound, viewed through the MIKE Zero GUI; (b) The same 400 turbines represented as porous plates for Delft3D. Higher values of the closs parameter, shown by bluer colours, indicate plates with higher drag. [Figure presented] Fig. 13: Changes in mean current speeds over 28 days as a result of adding turbines. [Figure presented] Fig. 14: Change in mean bed stress magnitude over 28 days as a result of adding turbines, expressed as a proportion of the value without turbines

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Clinical pharmacology as a foundation for translational science.

The evolution of enabling technologies and their associated perspectives into molecular mechanisms underlying disease has extended beyond the abilities of scientific and clinical structures to advance their translation into new algorithms that improve the health of patients and populations.1 Research programs have yielded a vast array of novel molecules related to pathophysiological mechanisms that represent diagnostic and therapeutic targets which have the potential for personalized healthcare management. Yet, despite extraordinary scientific advances, routine successful translation of discovery into new therapeutic tools remains a distant vision. Beyond constraints in bridging discovery science with clinical translation due to obstacles in facilities, resources and in skilled specialized investigators, 95% of therapies brought into product development by the pharmaceutical and biotechnology sector eventually fail, reflecting negative balance between efficacy and adverse effects

Impact of Menstrual Phases on Stress Markers: A Pilot Study

PURPOSE: Previous research has shown that different phases of the menstrual cycle may impact biometrics such as markers of stress and inflammation [e.g., cortisol (CORT), interleukin-6] as well as body composition. However, there is scarce literature regarding markers of stress and oxidative stress such as salivary a-amylase (sAA), immunoglobin-A (SIgA) and uric acid (UA), in relation to the four different menstrual phases. The purpose of this study was to examine the impact of menstrual phases on sAA, CORT, UA and SIgA. METHODS: 21 pre-menopausal women with regular menstrual cycles (n=9) oral contraceptive users (OC) and (n=12) non-oral contraceptive users (non-OC) recorded baseline cycle dates using the Flo Period Tracker appä. Participants began experimental testing after recording baseline dates, consisting of four total sessions with one session occurring during the 1) menses, 2) late follicular, 3) ovulatory and 4) late luteal phase. Salivary markers: CORT, sAA, UA, and SIgA, along with diastolic and systolic blood pressure (BP), total body water (TBW) and body fat percentage (BF%) were recorded during each phase. BF% and TBW were determined via InBody bioelectric-impedance analyzerä. 500uL of saliva was collected, with samples immediately frozen at -80°C until analysis. Saliva samples were centrifuged at 4°C for a duration of 15 minutes at 1500g prior to analysis and duplicated for CORT, sAA, UA and SIgA concentrations. Statistical procedures were conducted via SAS v 9.4 (Cary, NC). One way repeated measures analysis of variance was used to evaluate outcome measures as well as changes in salivary markers and body composition measurements across different menstrual cycle phases. Fisher’s Least Significant Difference test was used to compare means in the instance of a significant main effect (p \u3c 0.05). Partial eta squared (hp2) was run to determine effect size. RESULTS: sAA concentrations were significantly lower during the follicular phase compared menstruation phase (p = 0.006, ηp2 = 0.14). The main effect for SIgA approached significance (p = 0.05). There were no changes in CORT, UA, BF%, TBW or diastolic and systolic blood pressure. CONCLUSION: These findings suggest the menstrual cycle influences sAA concentrations in both OC users and non-OC users. More research needs to be conducted with a larger sample size in order to determine significance of SIgA in relation to menstrual phases

Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics