Organizational Learning from Extreme Performance Experience: The Impact of Success and Recovery Experience

This paper argues that two different types of a firm’s own extreme performance experiences—success and recovery—and their interactions can generate survival-enhancing learning. Although these types of experience often represent valuable sources of useful learning, several important learning challenges arise when a firm has extremely limited prior experience of the same type. Thus, we theorize that a certain threshold of a given type of experience is required before each type of experience becomes valuable, with low levels of experience harming the organization. Furthermore, we propose that success and recovery experience will interact to enhance each other’s value. These conditions can help overcome learning challenges such as superstitious learning or learning from small samples. We investigate our ideas using a sample of the U.S. commercial banks founded between 1984 and 1998. Our results indicate that both success and recovery experience of a firm generate survival-enhancing learning, but only after a certain level of experience is reached. Furthermore, success and recovery experience enhance each other’s learning value, consistent with the theories that emphasize the importance of richer and contrasting experience in providing useful knowledge. Our framework advances organizational learning theory by presenting a contingent model of the impact of success and recovery experience and their interaction

A conceptual model for migratory tundra caribou to explain and predict why shifts in spatial fidelity of breeding cows to their calving grounds are infrequent

Calving grounds of migratory tundra caribou (Rangifer tarandus) have two prominent characteristics. Firstly, the cows are gregarious, and secondly, the annual calving grounds spatially overlap in consecutive years (spatial fidelity). The location of consecutive annual calving grounds can gradually shift (either rotationally or un-directional) or more rarely, abruptly (non-overlapping). We propose a mechanism to interpret and predict changes in spatial fidelity. We propose that fidelity is linked to gregariousness with its advantages for individual fitness (positive density-dependence). Our argument is based on a curvilinear relationship between the density of cows on the calving ground (which we use to index gregariousness) and spatial fidelity. Extremely high or low densities are two different mechanisms which can lead to reduced spatial fidelity to annual calving grounds and reflect the caribou’s adaptive use of its calving ranges

Single copy/knock-in models of ALS SOD1 in C. elegans suggest loss and gain of function have different contributions to cholinergic and glutamatergic neurodegeneration

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) lead to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease that disproportionately affects glutamatergic and cholinergic motor neurons. Previous work with SOD1 overexpression models supports a role for SOD1 toxic gain of function in ALS pathogenesis. However, the impact of SOD1 loss of function in ALS cannot be directly examined in overexpression models. In addition, overexpression may obscure the contribution of SOD1 loss of function in the degeneration of different neuronal populations. Here, we report the first single-copy, ALS knock-in models in C. elegans generated by transposon- or CRISPR/Cas9- mediated genome editing of the endogenous sod-1 gene. Introduction of ALS patient amino acid changes A4V, H71Y, L84V, G85R or G93A into the C. elegans sod-1 gene yielded single-copy/knock-in ALS SOD1 models. These differ from previously reported overexpression models in multiple assays. In single-copy/knock-in models, we observed differential impact of sod-1 ALS alleles on glutamatergic and cholinergic neurodegeneration. A4V, H71Y, G85R, and G93A animals showed increased SOD1 protein accumulation and oxidative stress induced degeneration, consistent with a toxic gain of function in cholinergic motor neurons. By contrast, H71Y, L84V, and G85R lead to glutamatergic neuron degeneration due to sod-1 loss of function after oxidative stress. However, dopaminergic and serotonergic neuronal populations were spared in single-copy ALS models, suggesting a neuronal-subtype specificity previously not reported in invertebrate ALS SOD1 models. Combined, these results suggest that knock-in models may reproduce the neurotransmitter-type specificity of ALS and that both SOD1 loss and gain of toxic function differentially contribute to ALS pathogenesis in different neuronal populations.Peer reviewe

Health-related quality of life in KEYNOTE-010 : a phase II/III study of pembrolizumab versus docetaxel in patients with previously treated advanced, programmed death ligand 1-expressing NSCLC

Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score >= 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m(2) every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

"Help Me Help the AI": Understanding How Explainability Can Support Human-AI Interaction

Despite the proliferation of explainable AI (XAI) methods, little is understood about end-users' explainability needs. This gap is critical, because end-users may have needs that XAI methods should but don't yet support. To address this gap and contribute to understanding how explainability can support human-AI interaction, we conducted a study of a real-world AI application via interviews with 20 end-users of Merlin, a bird-identification app. We found that people express a need for practically useful information that can improve their collaboration with the AI system, and intend to use XAI explanations for calibrating trust, improving their task skills, changing their behavior to supply better inputs to the AI system, and giving constructive feedback to developers. We also assessed end-users' perceptions of existing XAI approaches, finding that they prefer part-based explanations. Finally, we discuss implications of our findings and provide recommendations for future designs of XAI, specifically XAI for human-AI collaboration

A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway

Cholesterol is one of the key constituents for maintaining the cellular membrane and thus the integrity of the cell itself. In contrast high levels of cholesterol in the blood are known to be a major risk factor in the development of cardiovascular disease. We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. Model stability analysis shows that the only positive steady-state of the system exhibits purely oscillatory, damped oscillatory or monotic behaviour under certain parameter conditions. In light of our findings we postulate how cholesterol homestasis is maintained within the cell and the advantages of our model formulation are discussed with respect to other models of genetic regulation within the literature