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

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

Racial-group differences in IQ in the Minnesota Transracial Adoption Study: A reply to Levin and

The etiology of racial differences in intelligence and achievement is one of the most heated areas of social science research. In this article, we respond to criticisms by Levin and Lynn of our 1992 follow-up study of IQ and achievement in a sample of transracial adoptees and their families, in particular to their assertion that our results provide strong support for a genetic etiology underlying racial differences in measured intelligence. In that follow-up, as well as in publications from the original study In this article, we address a number of issues raised in Levin's and Lynn's critiques, including the magnitude of adoptee racial-group differences in IQ and achievement, the inclusion of white and Asian/Indian adoptee groups in such analyses, the confounding of important early environmental influences with race differences, the confusion of withingroup and between-group influences on IQ, the regional U.S. differences in AfricanAmerican norms for IQ and achievement, the effects of renormed IQ tests on adoptee group differences, and the nature of the available evidence regarding a genetic hypothesis for racial differences in intelligence. We argue that, contrary to Levin's and Lynn's assertions, results from the Minnesota Transracial Adoption Study provide little or no conclusive evidence for genetic influences underlying racial differences in intelligence and achievement. Racial-group differences in intelligence and achievement are often observed but seldom explained to anyone's satisfaction. A variety of etiological speculations have been offered to explain such differences. These have included environmental factors, such as the pervasive effects of poverty The authors wish to acknowledge the helpful comments of an anonymous reviewer. Correspondence and requests for reprints should be sent t

The GUCY2C Tumor Suppressor is the Nexus of a Paracrine Hormone Axis Preventing Radiotherapy-Induced Gastrointestinal (GI) Toxicity

Purpose/Objective: Radiation-induced GI toxicity is the primary dose limitation compromising therapy in cancer patients treated with radiation therapy. GUCY2C is the intestinal receptor for diarrheagenic bacterial enterotoxins and the endogenous paracrine hormones guanylin and uroguanylin. Following genomic insult, cyclic (c)GMP produced by ligand activation of GUCY2C enhances DNA damage sensing and repair in intestinal cells. Here, we show that the GUCY2C-cGMP axis mediates p53-dependent radioprotection of intestinal epithelial cells. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

2003), Assessing the Impact of Organizational Practices on the Relative Productivity of University Technology Transfer Offices: An Exploratory

Abstract: We present quantitative and qualitative evidence on the relative productivity of university technology transfer offices (TTOs). Our empirical results suggest that TTO activity is characterized by constant returns to scale and that environmental and institutional factors explain some of the variation in performance. Productivity may also depend on organizational practices. Unfortunately, there are no quantitative measures available on such practices, so we rely on inductive, qualitative methods to identify them. Based on 55 interviews of 98 entrepreneurs, scientists, and administrators at five research universities, we conclude that the most critical organizational factors are faculty reward systems, TTO staffing/compensation practices, and cultural barriers between universities and firms. technology transfer offices | university/industry technology transfer | stochasti

Radiation arteritis: A contraindication to carotid stenting?

BackgroundCarotid artery stenting (CAS) for high-risk anatomic lesions is accepted practice. Neck irradiation and radiotherapy-induced arteritis are common indications. The clinical outcomes of CAS for radiation arteritis have been poorly defined.MethodsA prospective database of patients undergoing CAS at a tertiary referral academic medical center was maintained from 1999 to 2006. Patients undergoing primary carotid artery stenting for significant atherosclerotic (ASOD) and radiotherapy (XRT)-induced occlusive disease were analyzed. Life-table analyses were performed to assess time-dependent outcomes. Cox proportional hazard analysis or Fisher’s exact test was performed to identify factors associated with outcomes. Data are presented as the mean ± SEM unless otherwise indicated.ResultsDuring the study period, 150 patients underwent primary CAS, 75% with embolic protection. Fifty-eight percent were symptomatic. One hundred twenty-seven (85%) were treated for ASOD, and 23 (15%) had XRT. The 30-day all-cause mortality rate was 1% for ASOD and 0% for XRT (P = NS); overall survival at 3 years was equivalent. There was no significant difference in major adverse event rates as defined by the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial between the groups. The 3-year neurologic event-free rate was 85% for ASOD and 87% for XRT (P = NS). Late asymptomatic occlusions were seen only in XRT patients. The 3-year freedom from restenosis rate was significantly worse for the XRT group, at 20%, vs 74% for the ASOD group (P < .05). Likewise, the 3-year patency rate was also worse for the XRT group, at 91%, vs 100% for ASOD by Kaplan-Meier analysis (P < .05). No factor was predictive of occlusion or stenosis by Cox proportional hazards analysis.ConclusionCAS for radiation arteritis has poor long-term anatomic outcome and can present with late asymptomatic occlusions. These findings suggest that these patients require closer postoperative surveillance and raise the question of whether CAS is appropriate for carotid occlusive lesions caused by radiation arteritis

Supernova 2007bi as a pair-instability explosion

Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse progressively heavier elements in their centres, up to inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion -- an iron-core-collapse supernova (SN). In contrast, extremely massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs prior to oxygen ignition, and leads to a violent contraction that triggers a catastrophic nuclear explosion. Tremendous energies (>~ 10^{52} erg) are released, completely unbinding the star in a pair-instability SN (PISN), with no compact remnant. Transitional objects with 100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse supernovae following violent mass ejections, perhaps due to short instances of the pair instability, may have been identified. However, genuine PISNe, perhaps common in the early Universe, have not been observed to date. Here, we present our discovery of SN 2007bi, a luminous, slowly evolving supernova located within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding core mass to be likely ~100 M_{solar}, in which case theory unambiguously predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were synthesized, and that our observations are well fit by PISN models. A PISN explosion in the local Universe indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic limit, perhaps resulting from star formation processes similar to those that created the first stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009), including all supplementary informatio

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

GUCY2C lysosomotropic endocytosis delivers immunotoxin therapy to metastatic colorectal cancer.

The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for immunotoxins comprising a GUCY2C-directed monoclonal antibody conjugated through a reducible disulfide linkage to ricin A chain, which is activated to a potent cytotoxin in lysosomes. Indeed, this immunotoxin specifically killed GUCY2C-expressing colorectal cancer cells in a lysosomal- and clathrin-dependent fashion. Moreover, this immunotoxin reduced pulmonary tumors \u3e80% (