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Purpose Research on service innovation management of online travel agencies (OTAs) remains relatively scarce. This study aims to illuminate the detailed components of managing service innovations at OTAs. Design/methodology/approach An in-depth case study is conducted at Trip, the largest OTA in China. A coherent framework of managing service innovations at OTAs is proposed through refining an existing framework from new service development (NSD), and concerning the success factors of service innovation. Based on theoretical synthesis and empirical analysis, the NSD framework is adapted, restructured and refined for service innovation management at OTAs. Findings The proposed framework contains three facets and associated managerial elements: (1) resources, including stakeholders, technologies and systems; (2) contexts, including innovation strategy, structure and culture; and (3) ideation, including idea generation and idea application. Different success factors are attached to the managerial elements. The facets, managerial elements and success factors serve as the components in the framework. Research limitations/implications This study provides academia with an analytical framework to understand and interpret service innovation management at OTAs, which can be used as a point of departure for future research. Practical implications The analytical framework inspires OTA managers to adopt a structured approach in service innovation management, and policymakers to design related interventions. Originality/value This study offers a first step toward the investigation of service innovation management at OTAs, specifically in China. The proposed framework is potentially applicable to other industries.

This paper studies the initiation of a partnership between a corporation and a nongovernmental organization (NGO) for environmentally sustainable innovation, as well as its development over time. Proceeding from a dynamic capabilities approach, it provides a retrospective, longitudinal examination of a 10-year partnership between KLM Royal Dutch Airlines (KLM) and the World Wildlife Fund for Nature Netherlands (WNF), which promoted a market for aviation biofuels. The case study suggests that the progress of the partnership is determined by three specific dynamic capabilities of KLM and WNF: learning, coordination, and reconfiguration. The results reveal two microfoundations for each of these dynamic capabilities. For learning, these microfoundations are the sensing of strategic partners and the co-specialization of resources. For coordination, these consist of finding a fit between partners and having an integrated mission. Finally, the microfoundations of reconfiguration are the fostering of an institutional dialogue and the setting of new industry standards. This study is beneficial to scholars as it opens a research avenue concerning the dynamic capabilities and microfoundations that support corporate-NGO partnering for environmentally sustainable innovation. Practitioners can use these dynamic capabilities and microfoundations as guidelines for developing their own specific corporate-NGO partnerships.

An increasing digitalization in all aspects of life and work reshapes traditional assumptions about human creativity. Both scholars and practitioners raise many questions with regards to how to stimulate employee creativity in the digital work context. While there are many studies that examine predictors of employee creativity, little effort has been made thus far to synthesize these findings in way that would provide meaningful guidance to organizations and to provide bases for future research. With this paper we aim to contribute to filling this gap. We systematically review empirical studies on predictors of employee creativity published in the past 30 years and organize findings following an established human resources management framework: Ability−Motivation−Opportunity (AMO) theory. This organizing framework enables us to clearly depict how contextual factors (a) separately and (b) jointly influence individual employee creativity. Specifically, it enables us to depict two possible models—combination and multiplicative models—through which contextual factors interact with individual factors in predicting employee creativity. Through synthesizing evidence for each of the models, we demonstrate to scholars and practitioners what is known about the interactional effects of contextual and personal factors on employee creativity, and what still needs to be studied if we are to take the field of research on creativity in the digital era forward.

IntroductionThere is an urgent medical need to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and prevent undertreatment and overtreatment. The aim of this study was to identify biomarker profiles that may support the differentiation between ATB and LTBI and to validate these signatures.Materials and MethodsThe discovery cohort included adult individuals classified in four groups: ATB (n = 20), LTBI without prophylaxis (untreated LTBI; n = 20), LTBI after completion of prophylaxis (treated LTBI; n = 20), and healthy controls (HC; n = 20). Their sera were analyzed for 40 cytokines/chemokines and activity of adenosine deaminase (ADA) isozymes. A prediction model was designed to differentiate ATB from untreated LTBI using sparse partial least squares (sPLS) and logistic regression analyses. Serum samples of two independent cohorts (national and international) were used for validation.ResultssPLS regression analyses identified C-C motif chemokine ligand 1 (CCL1), C-reactive protein (CRP), C-X-C motif chemokine ligand 10 (CXCL10), and vascular endothelial growth factor (VEGF) as the most discriminating biomarkers. These markers and ADA(2) activity were significantly increased in ATB compared to untreated LTBI (p ≤ 0.007). Combining CCL1, CXCL10, VEGF, and ADA2 activity yielded a sensitivity and specificity of 95% and 90%, respectively, in differentiating ATB from untreated LTBI. These findings were confirmed in the validation cohort including remotely acquired untreated LTBI participants.ConclusionThe biomarker signature of CCL1, CXCL10, VEGF, and ADA2 activity provides a promising tool for differentiating patients with ATB from non-treated LTBI individuals.

The automobile industry is faced with societal and market pressures to develop radically innovative cars for the future. The development of the autonomous vehicle (AV) is a strategic innovation in this area. This paper studies whether and how AV-innovation strategies at Tesla, BMW and Toyota are developed by using an open and/or closed innovation paradigm. More than ever, it appears that R&D departments of car manufacturers employ a combination of a closed and an open innovation strategy. In order to nurture their AV innovation strategy, they strategically decide which innovations to adopt from outside, and which parts of the R&D process to keep in-house. This paper presents and discusses the combined closed-open AV-innovation strategies used by three dominant car producers. It provides an insight in how they aim to gain a first-to-market position and sustainable competitive advantage in a new market segment of a highly saturated market.

Background: Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions. Aim: A structured reflection could improve patients’ quality of life and spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being. Design: The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time. Participants: Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group. Results: A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life ( β = 0.52, adj. R2 = 0.26) and satisfaction with life ( β = 0.61, adj. R2 = 0.37). Conclusion: Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace.

Business model innovations emerge over time and are influenced by managerial interaction with stakeholders. Especially with regard to business model innovation for sustainability, manager-stakeholder interaction can radically change a company’s business model and underlying logic. However, the majority of the literature shows how manager–stakeholder interaction may limit business model innovation when stakeholders reinforce existing managerial cognitions. In this chapter we study how stakeholders can also stimulate business model innovation by affecting managerial cognitive change. Through three case studies, we find that this can occur through three shaping processes: market approach shaping, product/service offering shaping, and credibility shaping. We also find that the impact of new or latent stakeholders is greater than that of existing stakeholders. We end the chapter by sketching a research agenda to further unravel the role of stakeholders affecting managerial cognition around business model innovation for sustainability.

Oxygen concentration is an essential parameter in in vitro cell cultures as it affects cell viability, cellular activity, cell differentiation, and can be a measure for cellular response. Organ-on-chip (OoC) devices provide an in vitro cell culture method, aiming to mimic the in vivo situation better than conventional cell culture methods. Oxygen control in these OoC devices is very meaningful especially for organs with inherently large oxygen concentration gradients, such as the gut. Here, we show a versatile fabrication method for optical oxygen sensor patches based on platinum tetrakis (pentafluorophenyl) porphyrin (PtTFPP) in polystyrene (PS). The PtTFPP/PS sensors show a linear Stern Volmer calibration plot. The proposed fabrication method allows abundant design freedom regarding both the sensor patches (size and shape) and integration (site and number of patches) in a typical two-channel OoC device.

Background: A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Data on SARS-CoV-2 specific T-cell responses is scarce, but various studies suggest a suppressed T-cell mediated immunity in patients with COVID-19. Methods: The objective of the present study was to determine functional T-cell responses to SARS-CoV-2 antigens (mosaic surface protein and nucleoprotein), by using an enzyme-linked immunosorbent spot (ELISpot) interferon-γ release assay, in patients with RT-PCR confirmed COVID-19. T-cell immune responses were evaluated in patients with severe disease admitted to the intensive care unit (ICU), patients with moderate disease treated on the pulmonary ward and healthy volunteers. Findings: More than half of the 19 COVID-19 patients sampled at ≥14 days after the onset of symptoms showed a significant T-cell response against the nucleoprotein. A subgroup of nine (47%) of these 19 COVID-19 patients showed a delayed or reduced T-cell response against the nucleoprotein and showed significant lower reactivity against the mitogen control stimulant. Interpretation: As none of the healthy controls had more than nine IFN-γ spot forming cells specific for the SARS-CoV-2 nucleoprotein, 10 or more spots was determined to be indicative for COVID-19 disease. The SARS-CoV-2 nucleoprotein ELISpot of patient samples taken more than three weeks after the start of symptoms showed a high diagnostic sensitivity for COVID-19 disease. T-cell response in a subgroup of COVID-19 patients was suboptimal and supports previous studies in which patients with COVID-19 were associated with a suppressed T-cell mediated immunity. Funding Statement: N/A Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The regional Medical Research Ethics Committees United approved the study (Nieuwegein, the Netherlands; MEC-U: NL73618.100.20).

This study hypothesizes and empirically tests the influence of involvement of (1) frontline employees and (2) top managers in ideation process on healthcare service innovation quality. Based on data from 168 service innovation projects in Dutch healthcare organizations, the empirical results indicate that frontline employee involvement and top management involvement in, respectively, idea generation and idea application both improve the quality of healthcare service innovation. We find that the positive effect of frontline employee involvement is stronger under the condition of higher service innovativeness. In the direct relationship of top management involvement and healthcare service innovation quality, our data do not show such a moderating effect. The key and general managerial implication of the findings is that healthcare organizations are inspired to involve frontline employees in the idea generation processes and involve top managers in the idea application processes of service innovation projects, in order to improve innovation quality.

Drawing on an integration of service-dominant (S-D) logic and the dynamiccapabilities approach, this study focuses on the relatively under-researched issue of service innovation quality in healthcare services. We propose a conceptualframework for the relationships between user-induced and organisation-basedrenewal, and service innovation quality in the healthcare sector. By putting serviceinnovativeness and organisational renewal at the input side of the healthcareorganisations’ value creation process, and treating service innovation quality as anoutput, this study hypothesises direct relationships between these two ends. Weconducted an empirical study in the Dutch healthcare sector. Based on data from168 service innovation projects in Dutch healthcare organisations, the empiricalstudy verifies these hypothesised relationships. The results reveal that both service innovativeness and organisational renewal are significant antecedents of quality improvement of the healthcare service innovations in these projects. This study provides theoretical and managerial implications for improving the quality of healthcare service innovations. The key managerial insight is that healthcareorganisations are implicated to pay more attention to continuous renewal of valuepropositions to their users/patients, as well as to continuous renewal of theirorganisations’ functioning.

This article develops a model of sustainable energy demonstration projects, based on a review of 229 scientific publications on demonstrations in renewable and sustainable energy. The model addresses the basic organizational characteristics (aim, cooperative form, and physical location) and learning effects (technical, organizational, policy and market learning) of sustainable energy demonstration projects (prototyping, organizing, and market demonstrations). This article concludes that a main effect of the reviewed demonstrations is that these projects enable people to learn to further develop, apply and commercialize sustainable, renewable and clean energy technologies. They provide four specific learning opportunities; they 1) enable scientists and technicians to learn how to technically develop sustainable energy prototypes; 2) facilitate technicians and managers to learn to build an organization that produces these sustainable energy prototypes on a large(r) scale; 3) help public policy officers to learn to develop public policy that stimulates the commercialization process of these sustainable energy prototypes; and 4) support commercial professionals to learn how to bring sustainable energy prototypes to the market.

This article is concerned with the emergence of the science–business (SB) profession and the role of the SB professional (SBP) in both academia and business. Transferring science to markets can take a variety of routes depending on the stage of development and the people and skill sets involved. An SBP may co-develop opportunities for exploitation as part of a team in a university or in the business world in a spin-off or a mature company. In both settings, the SBP connects with scientists and co-develops knowledge or technology into an exploitable commodity. The need for this type of professional was the starting point for a new curriculum: a 3-year bachelor’s programme in science, business and innovation that integrates fundamental sciences (physics, chemistry, mathematics), life and health sciences, energy and sustainability sciences, business/social sciences, innovation and entrepreneurship. The authors provide the context and rationale for the development of the programme and discuss how it meets its objective to address a critical skills need in both academic and business sectors.

This literature review study presents and discusses the learning strategies of organizations participating in sustainable energy demonstration projects. It finds that academic, commercial, and governmental organizations build on six major learning strategies. The first learning strategy is to capture intellectual property and benefit from knowledge spillovers. The second learning strategy comprises the building of a series of prototypes that are technically and commercially fit for purpose. The third learning strategy aims at operating production plants that produce the prototypes on a large scale. The fourth learning strategy concentrates on exploiting learning curves in these production plants. The fifth learning strategy focuses on creating supply-demand networks that serve increasing markets. Finally, the sixth learning strategy is to develop governmental regulation and funding schemes that support the emergence of an industrial and societal institutional infrastructure for sustainable energy technology, based on the lessons learned from the demonstration projects. This study also finds that the six learning strategies are facilitated by four key behaviors of participants in demonstration projects, which are mutual trust-building, decision-making in favor of sustainable energy technology, learning-network building, and demonstration program development. To academics, this study provides a comprehensive insight into organizations’ learning strategies in sustainable energy demonstration projects, regarding learning directions and outcomes. Its contribution to practice is that it supports academic, commercial, and governmental organizations in managing their portfolio of learning strategies in new sustainable energy demonstration projects.

QuantiFERON (QFT) results near the cut-off are subject to debate. We aimed to investigate which borderline QFT results were due to Mycobacterium tuberculosis (Mtb)-specific responses or to test variability.In a contact investigation, tuberculin skin test (TST), QFT and T-SPOT.TB (T-SPOT) were performed in 785 BCG-unvaccinated contacts. Contacts with a low-negative (0.15), borderline (0.15-0.35), low-positive (0.35-0.70) or high-positive QFT (≥0.70 IU/mL) were compared with respect to exposure, TST and T-SPOT results. Development of active tuberculosis was assessed.Borderline QFT results occurred in threefold excess over test variability (p = 0.0027). In contacts with low-negative, borderline or positive QFT results, a positive TST occurred in 24.9%, 62.1% and 91.4% (p 0.0001) and a positive T-SPOT result in 6.3%, 41.3% and 86.4%, respectively (p 0.0001). Two-third (20/29) of contacts with a borderline and 14/16 (88%) with a low-positive QFT had a positive TST and/or T-SPOT, indicating probable Mtb-infection. During 12 years of follow-up, seven patients were diagnosed with active tuberculosis, two of whom after a low-positive QFT.In this study, most borderline and low-positive QFT results were Mtb-specific, showing the biological significance of a borderline QFT. The clinical relevance, however, will be most distinct in patients who are or will be immunocompromised.

Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using Borrelia burgdorferi strain B31 and various recombinant antigens, and subsequently, the number of Borrelia -specific interferon gamma (IFN-γ)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) ( P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) ( P ≤ 0.016). We conclude that the Borrelia ELISpot assay, measuring the number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs, correlates with exposure to the Borrelia bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis.

To the editor,A recent retrospective study in this journal on patients with confirmed tuberculosis (TB) suggested a limited role of QuantiFERON-TB Gold in-Tube (QFT-gold) in the diagnosis and treat...

Advanced age was the only risk factor for false-negative IGRAs in this study of active tuberculosis http://ow.ly/Cvp5G

Innovation is one of the increasingly important means by which companies can contribute to sustainable development. The shift of focus in business from competitiveness alone, to the combination of sustainability and competitiveness impacts firms’ capabilities for innovation. This process study aims to investigate what the organizational and managerial capabilities through which companies can innovate for sustainability are, referred to as dynamic capabilities for sustainable innovation. We address this question through a retrospective longitudinal case study of the attempts of the KLM Royal Dutch Airlines (KLM), which uses its influential position in the value chain to stimulate production and use of biofuel for aviation. The study identifies critical organizational and managerial capabilities that are forming the basis of the successful realignment of a firm’s dynamic capabilities with its sustainable innovation strategies. We explain how these capabilities are built and strengthened for sustainable innovation and how these capabilities function throughout the development process of sustainable innovation. This study aims to contribute to a further theoretical and practical understanding of how capabilities are deployed by firms to create and implement sustainable innovation.

Objective: To assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of a twenty-week power-assisted exercise intervention in people with profound intellectual and multiple disabilities and to evaluate the potential beneficial effects of this intervention. Design: Pilot randomised controlled trial. Setting: A large-scale twenty-four-hour residential facility in the Netherlands. Subjects: Thirty-seven persons with profound intellectual and multiple disabilities. Intervention: Participants in the intervention group received a power-assisted exercise intervention three times a week for thirty minutes over a twenty-week period. Participants in the control group received care as usual. Main measures: Trial feasibility by recruitment process and outcomes completion rates; intervention feasibility by programme compliance rates; potential outcomes by functional abilities, alertness, body composition, muscle tone, oxygen saturation, cardiovascular fitness and quality of life. Results: Thirty-seven participants were recruited ( M age = 32.1, SD = 14.6) and were randomly allocated to intervention ( n = 19) and control ( n = 18) groups. Programme compliance rates ranged from 54.2% to 97.7% with a mean (SD) of 81.5% (13.4). Oxygen saturation significantly increased in the intervention group. Standardised effect sizes on the difference between groups in outcome varied between 0.02 and 0.62. Conclusions: The power-assisted exercise intervention and the trial design were feasible and acceptable to people with profound intellectual and multiple disabilities living in a residential facility. This pilot study suggests that the intervention improves oxygen saturation, but further implementation with the aim of improving other outcomes should be considered with caution.

Background: The aim of this study was to evaluate the positive predictive value (PPV) of ELISpot in bronchoalveolar lavage (BAL) and pleural fluid for the diagnosis of active tuberculosis (TB) in real-life clinical practice, together with the added value of a cut-off >1.0 for the ratio between the extra-sanguineous and systemic interferon-gamma responses in positive samples.Methods: A retrospective, single-centre study was performed. Patients with positive ELISpot in BAL and pleural fluid were included.Results: The PPV for TB in patients with positive ELISpot in BAL (n = 40) was 64.9%, which increased to 82.6% for the ESAT-6 panel and 71.4% for the CFP-10 panel after the introduction of a cut-off >1.0 for the ratio between the BAL and blood interferon-gamma responses. In patients with positive ELISpot in pleural fluid (n = 16), the PPV for TB was 85.7%, which increased to 91.7% for the ESAT-6 panel and 92.3% for the CFP-10 panel after the introduction of a cut-off >1.0 for the ratio between the pleural fluid and blood interferon-gamma responses.Conclusions: This report describes the PPV of ELISpot in BAL and pleural fluid for the diagnosis of active TB in real-life clinical practice. The results indicate the possibility of an increase of the PPV using a cut-off >1.0 for the ratio between the extra-sanguineous and systemic interferon-gamma responses. Further studies are needed to underline this ratio-approach and to evaluate the full diagnostic accuracy of ELISpot in extra-sanguineous fluids like BAL and pleural fluid.

Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB).Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-gamma release assays or, as an alternative in individuals without a history of bacille Calmette-Guerin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis.Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-gamma release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB.This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

In view of the continuing global epidemic of tuberculosis (TB), adequate diagnosis is crucial for controlling this disease. Two commercial interferon gamma release assays (IGRA) have become available: the QuantiFERON-TB (QFT) and the T-SPOT.TB (TSPOT). They offer an important new tool for detecting both latent and active TB. In particular, the increased specificity as compared with the tuberculin skin test (TST) has resulted in many now (considering) replacing TST with IGRA.This review tries to offer the reader more insight from a clinical perspective into the applicability of IGRA for both latent and active TB.Although both IGRA are based on the same principle, they have marked different performance characteristics and it seems likely that both assays will establish their own niche. The increased specificity and sensitivity of IGRA in various settings as compared with TST show us that IGRA are here to stay. QFT might be the preferred tool for large-scale contact tracing, but in most clinical settings TSPOT has to be preferred. Much knowledge on IGRA has already been obtained in a short time; however, many questions remain unresolved, such as likelihood for developing active TB in individuals with a negative IGRA in contact tracing in various subgroups and the applicability of IGRA for detecting active TB.

This paper integrates the interorganisational innovation process and national innovation system-approach into a new model. A case study research project that covers a 16-year period of sustainable innovations in the Dutch residential building industry applies the model. The research outcomes indicate that interorganisational sustainable innovation processes contribute to the development of a national system of sustainable innovation. Additionally, a national sustainable innovation system facilitates, structures, and stimulates the development of interorganisational sustainable innovation processes. Copyright © 2009 Inderscience Enterprises Ltd.

This paper explores and explains the relationship between interorganizational sustainable innovation processes and the elements of a national sustainable innovation system in building. The literature proposes that this relationship is characterized by mutual reinforcement. This paper integrates the interorganizational innovation process- and the national innovation systems-approach into a new model. A case research project, that covers a sixteen-year period of sustainable innovations in the Dutch residential building industry, investigates the interplay between process and systematic sustainable innovation within the structure of the model. The research project indicates, illustrates, and explains how interorganizational sustainable innovation processes and a national sustainable innovation system in building co-develop in an interactive and mutually reinforcing process. In this process, the national system for sustainable innovation in building provides the structure in which the interorganizational sustainable innovative building processes develop. Simultaneously, the interorganizational sustainable innovative building processes stimulate the development of a national system of sustainable building innovation.

This article's subject is the cooperation process between organizations that develop and implement innovations in sustainable building. Its main research question is how governmental and commercial organizations organize and structure their joint activities to develop innovations in sustainability. In the search for answers to this question the cooperative activities of innovating organizations are modelled as an interorganizational innovation process. The case study research method is used to investigate the development of interorganizational innovation patterns in sustainability in seven house-building projects in the Dutch residential building sector. The empirical research findings are discussed by means of a comparison with the theoretical framework that includes five complementary stage models of interorganizational innovation processes. The main conclusions of the research are that (1) governmental and commercial organizations that successfully innovate in sustainability go through eight consecutive stages of interorganizational innovation, and (2) perform twenty-two interaction patterns that are part of these stages.

There is an ongoing debate on how firms can simultaneously generate resource-based and relational rents, i.e., how they can benefit from increasingly specialized knowledge and resources on the one hand, while also fulfilling relation-specific demands for adaptation that allow them to benefit more fully from their partnerships. We contend that firms with the capability to more effectively and efficiently (a) adapt their own resources to relational requirements, and (b) adapt their relationship’s resources to their own advantage face less of a tradeoff between resource-based and relational rents. Since different firms in a collaboration may preside over different levels of these adjustment and re-adjustment capabilities, they will have asymmetric incentives to invest in the collaboration, which impacts collaboration outcomes. Our argument explores underlying dynamics between the resource based and relational view in this regard as an important potential driver of boundary evolution. We apply our argument to two well-known joint ventures between Apple and IBM to illustrate and elucidate the key points.

A high percentage of pleural effusions remain unexplained despite an intensive diagnostic workup. Epstein-Barr virus (EBV) infections occur worldwide and affect the majority of the population. The present study investigated the prevalence and clinical relevance of EBV in pleural effusions. A prospective study was performed in which 60 consecutive patients with pleural effusion were enrolled. Real-time quantitative EBV-PCR was performed on pleural fluid and serum. Pleural fluid was further evaluated using standard biochemical, cytological and microbiological procedures. Demographic data, medical history and medication were recorded. A total of 24 (40%), from 60 pleural fluids tested, were positive in the EBV-PCR. Median EBV-DNA levels for positive samples was 454 genome equivalents (geq)·mL−1 (range 36–163,446 geq·mL−1). A total of 20 (59%) out of 34 unexplained pleural effusions were EBV-PCR positive. Serological analysis of all patients with a positive PCR revealed a previous infection. Patients with a positive EBV-PCR on pleural fluid were more likely to have a positive EBV-PCR on serum than patients with a negative PCR on pleural fluid. Epstein-Barr virus reactivation in pleural fluid is a frequent event and the absence of an alternative diagnosis to explain the nature of the effusion in the majority of cases suggests an aetiological role for Epstein-Barr virus in the development of pleural effusion.

We have read the recently published review of Aggarwal and colleagues ([1][1]) with great interest. The use of interferon gamma release assays (IGRA) in extrasanguineous body fluids as potential diagnostic tests for active tuberculosis (TB) does have our special attention. We would like to address

Strategic ambitions can function as drivers of improvement in organizations. Continuous improvement is driven by strategic ambitions to: design quality into the structure of the organization; plan and control improvements; assure improvements; set and realize improvement goals; position the organization in the market as a “high quality” organization; and create value in interaction with stakeholders. An analytical framework based on these drivers is described. A research project is carried out in the organization of DaimlerChrysler Netherlands. The improvement processes in this organization are analyzed with the framework. The research project indicates that the improvement processes are driven by the strategic ambitions of the organization. © 2002, MCB UP Limited

Quality management practices do support the management of strategically important innovation processes. This conclusion is based on empirical research in the Dutch construction industry. A large‐scale innovative construction project is intensively studied during a three‐year period. The quality management practices that are used in this project to support the management of strategically important innovation processes are described and analyzed. The description and analysis is based on an analytical framework that consists of six quality management practices: design, planning, systems, goal, positioning, and interaction practices. The analytical framework is based on a theoretical study in the field of strategic quality management. The empirical research points out that planning, positioning and interaction practices in quality management support the management of strategic innovation. It also indicates that systems and goal practices in quality management can be supportive to the management of strategic innovation.

Most research on creativity shows that importance of leadership behaviors. In this multilevel study, we shift the focus of leaderships in a narrow sense by exploring the relationship among entrepre...

The demonstration project can be an effective organizational form to transform a clean technology prototype - for example, in the field of photovoltaics, carbon capture and storage, or wind power - into a marketable product. A question with regard to the clean technology demonstration project is how its effectiveness can be increased. This article answers this question by reviewing scientific literature on clean technology demonstration projects of the past 39 years. It distinguishes and analyzes three types of demonstration projects: the technical demonstration, organizational demonstration, and market demonstration. The article proposes that the effectiveness of demonstration projects increases when clean technology prototypes are tested, improved, and marketed successively. First, they should be tested in technical demonstrations, then improved in organizational demonstrations, and finally marketed in market demonstrations. The article also proposes five managerial factors that stimulate the effectiveness of the three consecutive demonstration types. The article concludes with an agenda for future research, concentrating on the diffusion of clean technological innovations through a coherent program of demonstration projects. It presents several theoretical approaches that can be applied to conduct future demonstration project research.

SummaryTo evaluate the contribution of an imbalance between coagulation activation and fibinolysis activation and inhibition to morbidity and mortality in sepsis, we determined in medical hospitalized patients at inclusion (day 0) for fever (temperature above 38.0° C axillary or 38.3° C rectally), and daily thereafter for two days, circulating thrombin-antithrombin III (TAT) complexes, plasmin- 2-antiplasmin (PAP) complexes (day 0 only), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and interleukin (IL)-6, the latter as a marker of the inflammatory host response. Study variables were 1) positive microbiological results for specimens from local sites associated with a clinical infection, positive blood cultures (including parasitemia) or both, within 7 days after inclusion, 2) development of shock, i.e. systolic blood pressure

Predictors among demographic, clinical, and laboratory variables for a microbial (nonviral/nonchlamydial) infection in hospitalized medical patients with new onset of fever (temperatureor =38.0 degrees C axillary oror =38.3 degrees C rectal) were analyzed and compared with the criteria for the systemic inflammatory response syndrome (SIRS), including an abnormal body temperature and WBC count, tachypnea and tachycardia, and sepsis, defined as SIRS and the presence of a clinical infection.A prospective cohort study.Department of internal medicine at a university hospital.In 300 hospitalized medical patients with new onset of fever, demographic, clinical, and laboratory variables were obtained during the first 2 days after inclusion, and peak and nadir values, when appropriate, were taken. Microbiologic results for 7 days were collected. Clinical information was used to decide on the presence of a clinical infection.One hundred thirty-three of 300 patients (44%) had a microbial infection: 26% suffered from local microbial infection only, 9% from bacteremia only, and 9% had bloodstream plus local microbial infections. Patients with a microbial infection had a higher World Health Organization performance score at home (p0.05), higher peak body temperature (p0.001), higher nadir and peak WBC counts (p0.05), lower nadir platelet count (p0.01), higher peak alanine and aspartate aminotransferases (p0.01), and lower nadir albumin (p0.001) levels in blood during the first 2 days after inclusion than those without infection. Using multivariate techniques, predictors for microbial infection or bacteremia alone, independent of age, sex, underlying disease, and clinical infection, were peak temperature, peak WBC count, and nadir platelet count and albumin level. In contrast, conventional SIRS/sepsis definitions and criteria predicted microbial infection less well, mainly because tachypnea and tachycardia were of no predictive value.In febrile medical patients, microbial infection can be predicted with use of easily obtained clinical and laboratory variables, including peak temperature, peak WBC count, and nadir platelet count and albumin level within the first 2 days. The new model predicted microbial infection better than conventional SIRS/sepsis criteria. This may help to improve the clinical recognition of the systemic host response to microbial infection and to refine SIRS/sepsis definitions.

Fever suggests the likelihood of severe microbial infection. Abnormal temperature, tachycardia, tachypnea, and abnormal white blood cell counts define the systemic inflammatory response syndrome (SIRS). In 300 hospitalized medical patients with fever, we determined clinical variables and procalcitonin, elastase-α 1 -antitrypsin, and lactoferrin levels in plasma. Of the patients, 71% had clinical infection (by clinical judgment) and 44% had microbial infection (by microbiological testing). SIRS occurred in 95%, and the 28-day mortality rate was 9%. The sensitivity for predicting microbial infection, bacteremia, and mortality was less but the specificity was greater for supranormal procalcitonin, elastase-α 1 -antitrypsin, and lactoferrin levels than for SIRS. The area under the receiver operating characteristic curve (AUC) for microbial infection was higher for procalcitonin and elastase-α 1 -antitrypsin levels than for clinical variables and lactoferrin level. The AUC for bacteremia was also higher for inflammatory factors (>0.70; P

The present brief report describes four cases with mycobacterial infection and negative T-SPOT TM . TB tests. This test proved to be a useful tool to help rule out the diagnosis of active Mycobacterium tuberculosis infection and could therefore prevent unnecessary or inappropriate therapy.

Study objectives The aim was to evaluate demographic, clinical, and laboratory variables in febrile patients, with or without a microbiologically confirmed infection, for prediction of death, in comparison to the systemic inflammatory response syndrome (SIRS) and its criteria, such as abnormal temperature, tachycardia, tachypnea, and abnormal WBC count, and to sepsis, that includes SIRS and an infection. Design A prospective cohort study. Setting Department of internal medicine at a university hospital. Patients In 300 consecutive, hospitalized medical patients with new onset of fever, demographic, clinical, and laboratory variables were obtained during the 2 days after inclusion, while microbiological results for a follow-up period of 7 days were collected. Patients were followed up for survival or death, up to a maximum of 28 days after inclusion. Measurements and results Of all patients, 95% had SIRS, 44% had sepsis with a microbiologically confirmed infection, and 9% died. A model with a set of variables all significantly (p Conclusions In comparison to SIRS and sepsis, the new set of variables predicted mortality better for all patients with fever and also for those with microbiologically confirmed infection only. This type of effort may help in refining definitions of SIRS and sepsis, based on prognostically important demographic, clinical, and laboratory variables that are easily obtainable at the bedside.

A significant part of waste generation is caused by the building and construction industry. Reduction of construction waste is therefore a major topic of the integrated chain management policy of the Dutch government. Construction companies benefit from reduced waste generation by lower deposition costs and lower purchasing costs of virgin materials. An overview is presented of the main policy areas of the Dutch government concerning sustainability. Reducing the generation of construction waste fits into this policy. Subsequently, an overview is presented from construction-waste data available in literature. Then, the waste generation during several Dutch residential construction projects has been quantified and analyzed in detail. It follows that about 1-10% by weight of the purchased construction materials, depending on the material, leave the site as waste. Furthermore, the analyses identify additional sources of waste generation as those already known, such as a lack of attention paid to the sizes of the used products, lack of influence of contractors, and lack of knowledge about construction during design activities.

In this case series, we describe four cases in which the use of gamma interferon release assays with purified protein derivative (PPD) as a stimulating antigen was able to demonstrate PPD-specific immune activation. This may help to improve the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after intravesical BCG instillations for bladder carcinoma.

To the Editors: Tuberculosis (TB) remains a major global health problem. A major factor contributing to the current TB epidemic is the resistance of Mycobaterium tuberculosis to first-line anti-TB treatment. Therefore, there is a need for an appropriate and reliable tool to evaluate treatment efficacy. Several studies using the T-SPOT®. TB assay (Oxford Immunotec Ltd, Oxford, UK) reported a decline in the number of spots after successful anti-TB treatment, particularly in the 6-kDa early secretory antigenic target (ESAT-6) panel [1–3]; however, to our knowledge, no data have been published on cured TB patients who contracted TB before isoniazid and rifampicin became available. Therefore, the naturally long-term range of ESAT-6- and culture filtrate protein (CFP)-10-specific T-cell responses in patients with TB who did not receive modern anti-TB treatment is not known. Because most patients in prior studies were born in high-burden, TB-endemic countries, the T-cell kinetics might be influenced by reinfection. Therefore, the aim of this report is to compare the ESAT-6- and CFP-10-specific T-cell responses in a low-burden country with a low risk of reinfection between patients with a history of active TB before 1955, and patients with recently treated active TB. Venous blood for T-SPOT®. TB was collected from 24 outpatient subjects with a history of active TB before 1955 (group 1), obtained by clinical history-taking, patients’ medical records or documentation of a sanatorium admission. 16 of these patients had been admitted to a sanatorium, two patients underwent surgery and six patients were treated at home with para-aminosalicylic acid therapy or bedrest. Furthermore, 27 patients with recent active TB (group 2) were prospectively enrolled between March and May 2008. Active TB was defined as fulfilling one or more of the following criteria: 1) positive culture for M. tuberculosis (n=22); 2) positive PCR for M. …

Tuberculous pericarditis is a rare disease in developed countries. The diagnosis is difficult to set since there are no robust rapid tests, and culture of pericardial fluid forMycobacterium tuberculosisis often negative. T-SPOT.TB, an enzyme-linked immunospot (ELISPOT) test, measures the gamma interferon response of lymphocytes against tuberculosis antigens and can be performed on blood and body fluids. We describe a patient with tuberculous pericarditis for which the diagnosis was rapidly set by positive T-SPOT.TBresults, which were confirmed by isolation ofMycobacterium tuberculosisin pericardial fluid culture. We performed a literature search to assess the diagnostic potential of ELISPOT testing in tuberculous pericarditis. The limited data on this subject indicate that T-SPOT.TBaids in diagnosing active tuberculosis (TB) infection and results in a more rapid decision to start antituberculosis treatment. Enumerating TB-specific lymphocytes and testing blood/compartmental fluid simultaneously can provide useful information on active tuberculous pericarditis.