Reproducibility of in vitro contracture test results in patients tested for malignant hyperthermia susceptibility.

BACKGROUND: The in vitro contracture test (IVCT) is the golden standard to diagnose malignant hyperthermia susceptibility (MHS). A high reproducibility is important for a high validity of a test. METHODS: We have therefore analyzed IVCT in 838 patients, investigated in two laboratories. Each halothane and caffeine test was performed in two muscle strips. The test results were analyzed with respect to reproducibility of abnormal outcomes within pairs of tested muscle strips and size of contractures, thresholds and quality criteria. The patients were tested according to the European Malignant Hyperthermia Group protocol (EMHG). To fulfill quality criteria in the EMHG protocol the twitch height should be 10 mN (1 g) or more. For the caffeine test a minimum contracture of 50 mN (5 g) or more at 32 mmol l-1 caffeine could be used as an alternative quality criterion RESULTS: There was better reproducibility with larger contractures. The correlation between size of contractures and fraction of muscle strips with abnormal contractures was 0.77 or larger. Contractures < 5 mN (0.5 g) were reproducible in less than half of the tests. There was no difference in reproducibility or size of contractures between tests fulfillling all quality criteria and those not fulfillling these criteria. CONCLUSIONS: IVCT responses close to cut off limits, i.e. <5 mN (0.5 g) in the EMHG protocol, are less reproducible and must scientifically be considered as less reliable. The clinical cut off limits must remain unchanged for reasons of clinical safety. The outcome of quality measurements does not influence the test results

Inertia, Knowledge Sources and Diversity in Collaborative Problem-solving

Innovation is at the core of firms’ competitiveness. External knowledge is increasingly leveraged in the efforts to increase innovation performance by solving innovation related problems and thereby developing new technology, products or services. Using internal knowledge sources can be beneficial when pursuing minor performance improvements in existing technologies. However, reliance on internal knowledge sources carries a risk of organizational inertia related to problem understanding and solution development in the shape of path-dependencies and preferences for exploitation and reapplication of existing knowledge. Such inertia may imbue innovation processes related to the development of new technologies with reduced novelty and an inability to recognize alternative and potentially more attractive solutions. As a result, over-reliance on internal knowledge sources is likely to inhibit the ability to solve problems and reduce innovation performance related to the development of new technology. In contrast, a growing stream of research shows the positive effect on problem-solving and innovation performance from drawing on diverse knowledge sources outside the firm. Through collaborative efforts involving universities, customers, competitors and suppliers in problem-solving firms can gain complementary perspectives, insights and technological knowledge as they pursue the development of innovative technologies

The Influence of Strategic Interest Alignment on External Knowledge Search

This paper analyzes how external search is affected by strategic interest alignment among knowledge sources. I focus on misalignment arising from the heterogeneous effects of disruptive technologies by analyzing the influence of incumbents on 2,855 non-incumbents? external knowledge search efforts. The efforts most likely to solve innovation problems obtained funding from the European Commission?s 7th Framework Program (2007-2013). The results show that involving incumbents improves search in complementary technologies, while demoting it when strategic interests are misaligned in disruptive technologies. However, incumbent sources engaged in capability reconfiguration to accommodate disruption improve search efforts in disruptive technologies. The paper concludes that the value of external sources is contingent on more than their knowledge. Specifically, interdependence of sources in search gives rise to influence from individual strategic interests on the outcomes. More generally, this points to the need for understanding the two-way influence of sources, rather than viewing external search as one-way knowledge accessing

Decreased fertility rates in 9639 women diagnosed with inflammatory bowel disease: a United Kingdom population-based cohort study

Background: Clinical studies have reported reduced fertility in women with inflammatory bowel disease (IBD). Aim: To compare fertility rates in women with IBD to those in women without IBD and assess whether the relative fertility differed following IBD diagnosis, flares and surgery. Methods: Women aged 15-44 years in 1990-2010 were identified from a UK primary care database. We estimated overall and age-specific fertility rates by 5-year age bands for women with and without IBD. We used Poisson regression to calculate adjusted fertility rate ratios (AFRR), adjusted for age, smoking and socioeconomic deprivation. Results: There were 46.2 live births per 1000 person-years [95% confidence interval (95% CI); 44.6-47.9] in 9639 women with IBD and 49.3 (95% CI 49.2-49.5) in 2 131 864 without (AFRR: 0.93; 95% CI: 0.89-0.96). Excluding periods of contraception use, the AFRR was 0.99 (95% CI: 0.95-1.03). Before diagnosis, the AFRR for women with ulcerative colitis (UC) was 1.07 (95% CI: 0.99-1.16) and was 0.88 (95% CI: 0.81-0.97) for women with CD. After diagnosis, AFRRs were 0.87 (95% CI: 0.82-0.94) for CD and 0.92 (95% CI: 0.86-1.00) for UC. The fertility rate was lower following flares (AFRR: 0.70; 95% CI: 0.59-0.82) or surgery (AFRR: 0.84; 95% CI: 0.77-0.92). Women with pouch and non-pouch surgery had similar overall fertility though the reduction after surgery was greater for pouches (AFRR: 0.48; 95% CI: 0.23-0.99). Conclusions: Women with Crohn's disease have marginally lower fertility rates. These rates decreased following flares and surgical interventions. Fertility rates returned almost to normal when women were not prescribed contraception but the reduction following surgical intervention remained. As the lifetime effect of pouch vs. nonpouch surgery on fertility is small, the reduction post-pouch surgery should be interpreted with caution