Panel Discussion: Knowledge Management in Organizations: Issues, Problems and Directions for Research and Practice

Knowledge Management is currently recognized as the central challenge facing organizations today. As we move into the information economy, the basis of competition shifts from physical assets to intangible assets and the ability of firms to coordinate and leverage the deployment of intellectual capital of the firm become the central determinants of firm performance. This panel will discuss different facets of the phenomenon and suggest directions for IS research in the area

Specific IgE Response to Purified and Recombinant Allergens in Latex Allergy

Background In recent years, allergy to natural rubber latex has emerged as a major allergy among certain occupational groups and patients with underlying diseases. The sensitization and development of latex allergy has been attributed to exposure to products containing residual latex proteins. Although improved manufacturing procedures resulted in a considerable reduction of new cases, the potential risk for some patient groups is still great. In addition the prevalent cross-reactivity of latex proteins with other food allergens poses a major concern. A number of purified allergens and a few commercial kits are currently available, but no concerted effort was undertaken to evaluate them. Methods We studied 11 purified latex allergens, Hev b 1 to Hev b 10, and Hev b 13 along with several crude allergen extracts and two commercial ImmunoCAP assays to evaluate specific IgE antibody in the sera from latex allergic patients and controls. Health care workers and spina bifida patients with clinical symptoms of latex allergy, spina bifida patients without latex allergy, and non-atopic health care workers have been studied. Results The results suggest that Hev b 2, 5, 6, and 13 together identified over 80 percent health care workers with latex allergy, while Hev b 6 along with Hev b 1 or 3 detected specific IgE antibody in all sera studied from patients with spina bifida and latex allergy. The ImmunoCAP results using both Hev b 5 amplified and non-amplified closely agreed with the clinical diagnosis of latex allergy in health care workers and in spina bifida. Conclusion Although the purified allergens and crude extracts reacted diversely with IgE from different patient groups, the results indicated that use of certain combinations of purified recombinant antigens will be useful in commercial kits or in in-house assays for detecting specific IgE antibody in the sera. The results suggest that a combination of Hev b 2, 3, 5, 6, and 13 together detected specific IgE in 80% of the sera from latex allergic patients. Both ImmunoCAPs correctly identified over 95% of latex allergic patients, however, showed reactivity with a few normal control subject

TRX: A Formally Verified Parser Interpreter

Parsing is an important problem in computer science and yet surprisingly little attention has been devoted to its formal verification. In this paper, we present TRX: a parser interpreter formally developed in the proof assistant Coq, capable of producing formally correct parsers. We are using parsing expression grammars (PEGs), a formalism essentially representing recursive descent parsing, which we consider an attractive alternative to context-free grammars (CFGs). From this formalization we can extract a parser for an arbitrary PEG grammar with the warranty of total correctness, i.e., the resulting parser is terminating and correct with respect to its grammar and the semantics of PEGs; both properties formally proven in Coq.Comment: 26 pages, LMC

Work-Related Mental Health and Job Performance: Can Mindfulness Help?

Work-related mental health issues such as work-related stress and addiction to work impose a significant health and economic burden to the employee, the employing organization, and the country of work more generally. Interventions that can be empirically shown to improve levels of work-related mental health – especially those with the potential to concurrently improve employee levels of work performance – are of particular interest to occupational stakeholders. One such broad-application interventional approach currently of interest to occupational stakeholders in this respect is mindfulness-based interventions (MBIs). Following a brief explication of the mindfulness construct, this paper critically discusses current research directions in the utilization of mindfulness in workplace settings and assesses its suitability for operationalization as an organization-level work-related mental health intervention. By effecting a perceptual-shift in the mode of responding and relating to sensory and cognitive-affective stimuli, employees that undergo mindfulness training may be able to transfer the locus of control for stress from external work conditions to internal metacognitive and attentional resources. Therefore, MBIs may constitute cost-effective organization-level interventions due to not actually requiring any modifications to human resource management systems and practises. Based on preliminary empirical findings and on the outcomes of MBI studies with clinical populations, it is concluded that MBIs appear to be viable interventional options for organizations wishing to improve the mental health of their employees

Design, expression and characterization of mutants of fasciculin optimized for interaction with its target, acetylcholinesterase

Predicting mutations that enhance protein–protein affinity remains a challenging task, especially for high-affinity complexes. To test our capability to improve the affinity of such complexes, we studied interaction of acetylcholinesterase with the snake toxin, fasciculin. Using the program ORBIT, we redesigned fasciculin's sequence to enhance its interactions with Torpedo californica acetylcholinesterase. Mutations were predicted in 5 out of 13 interfacial residues on fasciculin, preserving most of the polar inter-molecular contacts seen in the wild-type toxin/enzyme complex. To experimentally characterize fasciculin mutants, we developed an efficient strategy to over-express the toxin in Escherichia coli, followed by refolding to the native conformation. Despite our predictions, a designed quintuple fasciculin mutant displayed reduced affinity for the enzyme. However, removal of a single mutation in the designed sequence produced a quadruple mutant with improved affinity. Moreover, one designed mutation produced 7-fold enhancement in affinity for acetylcholinesterase. This led us to reassess our criteria for enhancing affinity of the toxin for the enzyme. We observed that the change in the predicted inter-molecular energy, rather than in the total energy, correlates well with the change in the experimental free energy of binding, and hence may serve as a criterion for enhancement of affinity in protein–protein complexes

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial

Bruton’s tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35) randomized 93 adults with antihistamine-refractory CSU to 50 mg daily, 150 mg daily and 200 mg twice daily of fenebrutinib or placebo for 8 weeks. The primary end point was change from baseline in urticaria activity score over 7 d (UAS7) at week 8. Secondary end points were the change from baseline in UAS7 at week 4 and the proportion of patients well-controlled (UAS7 ≤ 6) at week 8. Fenebrutinib efficacy in patients with type IIb autoimmunity and effects on IgG-anti-FcεRI were exploratory end points. Safety was also evaluated. The primary end point was met, with dose-dependent improvements in UAS7 at week 8 occurring at 200 mg twice daily and 150 mg daily, but not at 50 mg daily of fenebrutinib versus placebo. Asymptomatic, reversible grade 2 and 3 liver transaminase elevations occurred in the fenebrutinib 150 mg daily and 200 mg twice daily groups (2 patients each). Fenebrutinib diminished disease activity in patients with antihistamine-refractory CSU, including more patients with refractory type IIb autoimmunity. These results support the potential use of BTK inhibition in antihistamine-refractory CSU

Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one‐year extension study

Background: Ligelizumab, a next-generation, humanized anti-immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard-of-care therapy. Objective: To evaluate the long-term safety and re-treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study. Methods: This open-label, single-arm, long-term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose-finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post-treatment for 48 weeks. Results: Overall, ligelizumab was well-tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment-emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks. Conclusion: The long-term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re-treatment efficacy was shown. Trial registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218

Ten myths about work addiction

Research into work addiction has steadily grown over the past decade. However, the literature is far from unified and there has been much debate on many different issues. Aim and methods: This paper comprises a narrative review and focuses on 10 myths about work addiction that have permeated the psychological literature and beyond. The 10 myths examined are (a) work addiction is a new behavioral addiction, (b) work addiction is similar to other behavioral addictions, (c) there are only psychosocial consequences of work addiction, (d) work addiction and workaholism are the same thing, (e) work addiction exclusively occurs as a consequence of individual personality factors, (f) work addiction only occurs in adulthood, (g) some types of work addiction are positive, (h) work addiction is a transient behavioral pattern related to situational factors, (i) work addiction is a function of the time spent engaging in work, and (j) work addiction is an example of overpathogizing everyday behavior and it will never be classed as a mental disorder in the DSM. Results: Using the empirical literature to date, it is demonstrated that there is evidence to counter each of the 10 myths. Conclusion: It appears that the field is far from unified and that there are different theoretical constructs underpinning different strands of research