Suchergebnisse

To survive and grow in an era of uncertainty, companies should strive not only for a single visionary view, which most likely corresponds with their expectations, but instead they should try to acquire multiple views that describe the whole "window of opportunities". The development of external market scenarios to assess current strategies is the usual way of coping with these uncertainties. Today this traditional scenario approach has to be extended in four directions: the use of market scenarios to systematically develop future‐robust strategies, the use of alternative strategy scenarios to address uncertainties within an organization, the use of scenarios as a basis for strategic early warning processes and the combination of performance measurement and strategic early warning in a scenario‐based future scorecard. In conclusion it is shown that scenarios could significantly help to bridge the gap between strategy implementation and early‐warning processes.

OBJECTIVES: Serum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be used to predict outcome, studies are required to demonstrate baseline NfL predicts future dementia risk. Furthermore, if it is to be used as a surrogate marker in clinical trials, change in NfL over time periods typical of a clinical trial must be linked to clinical progression. In a longitudinal study of patients with lacunar stroke and confluent white matter hyperintensities, we determined whether both baseline, and change, in NfL levels were linked to changes in MRI markers, cognitive decline and dementia risk. METHODS: Patients underwent MRI, cognitive testing and blood taking at baseline and annually for 3 years. Clinical and cognitive follow-up continued for 5 years. RESULTS: NfL data were available for 113 subjects for baseline analysis, and 90 patients for the longitudinal analysis. Baseline NfL predicted cognitive decline (global cognition β=-0.335, SE=0.094, p=0.001) and risk of converting to dementia (HR=1.676 (95% CI 1.183 to 2.373), p=0.004). In contrast to imaging, there was no change in NfL values over the follow-up period. CONCLUSIONS: Baseline NfL predicts changes in MRI markers, cognitive decline and dementia rate over a 5 years follow-up period in SVD, suggesting NfL may be a useful prognostic marker. However, change in NfL values was not detected, and therefore NfL may not be a useful surrogate marker in clinical trials in SVD. ; European Union's Horizon 2020 research and innovation programme under grant agreement No 667375 (CoSTREAM) Priority Programme Grant from the Stroke Association (award reference PPA 2015/02)

IMPORTANCE: Unrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease. OBJECTIVE: To assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding. EXPOSURES: Serum NfL concentrations measured using an ultrasensitive single-molecule array assay (Simoa). MAIN OUTCOMES AND MEASUREMENTS: Log-transformed sNfL concentrations in case patients and control individuals compared using conditional logistic regression and linear mixed models. RESULTS: Mean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, ...