Severe communication delays are independent of seizure burden and persist despite contemporary treatments in SCN1A + Dravet syndrome: Insights from the ENVISION natural history study

Objective: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment‐resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. Methods: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent‐reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6–2:0 years:months (Y:M; youngest), 2:1–3:6 Y:M (middle), and 3:7–5:0 Y:M (oldest). Results: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow‐up was 17.5 months (range = .0–24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum–maximum] = 1.0 in the youngest [1.0–70.0] and middle [1.0–242.0] age groups and 4.5 [.0–2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, p = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. Significance: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age

Examining the Penrose effect in an international business context: the dynamics of Japanese firm growth in US industries

Penrose (1959) theoretically developed the research proposition that the finite capacities of a firm's internally experienced managers limit the rate at which the firm can grow in a given period of time. One empirical implication that follows logically from this line of reasoning is that a fast-growing firm will eventually slow down its growth in the subsequent time period because its firm-specific management team, which is posited to be inelastic at least in the short run, is unable to handle effectively the increased demands that are placed on these internally experienced managers due to increased complexity as well as the time and attention that the new managers require from these internally experienced managers. Consequently, inefficiency in the firm's current operations will follow if the firm maintains its high rate of growth. The research proposition that a firm cannot remain operationally effective if it maintains high rates of growth in successive time periods, and that consequently those firms with foresight typically will slow down their growth in the subsequent time period is known as the 'Penrose effect' in the research literature, and this effect of dynamic adjustment costs has been examined and corroborated in a few empirical research studies. However, researchers have not yet examined the Penrose effect in an international business context. The current paper examines the Penrose effect in an international business context by exploring under what conditions Japanese firms achieve high growth in consecutive time periods in the entered US industries. The empirical results indicate that, consistent with Penrose's (1959) resource- based theory prediction, Japanese multinational firms that entered in US industries where the extent of knowledge tacitness, globalization, and unionization was high, rapid expansion growth in one time period had negative impacts on growth in the subsequent time period. Thus, dynamic adjustment costs limit the rate of the growth of the firm and the development of dynamic capabilities in this international business context, which suggests that the Penrose effect may be widely applicable to international business and corporate strategy. Copyright © 2005 John Wiley & Sons, Ltd.

Explaining autonomy variations across value-chain activities in foreign-owned subsidiaries

This article is one of the first to combine the asset bundling model and neo-configurational perspective to explain autonomy variations across different value-chain activities in foreign-owned subsidiaries. We develop tentative answers to three research questions based on survey data of subsidiaries located in Taiwan and Thailand. We use fuzzy set qualitative comparative analysis technique to analyze the data. We found that competence bundles in primary and support activities are key for autonomy development across basic and advanced value-adding activities. Strong relationships with local business networks are more important for autonomy development than links to universities or governmental institutions. The global city location plays a lesser role than expected and the geographic distance is a hindrance to autonomy development in basic as well as advanced value-chain activities