Coupled NOFLOW-FIPDIF Computer Program

This report describes the Coupled NOFLOW-FIPDIF computer program which has been written to perform the following two related functions: (1) Determination of the temperature attained by reactor materials following a loss of coolant accident. (2) Evaluation of the fission product inventory which would exist at any time (following loss of coolant)

Therapeutic strategies for C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia

Purpose of review An intronic G4C2 expansion mutation in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Although there are currently no treatments for this insidious, fatal disease, intense research has led to promising therapeutic strategies, which will be discussed here. Recent findings Therapeutic strategies for C9-ALS/FTD have primarily focused on reducing the toxic effects of mutant expansion RNAs or the dipeptide repeat proteins (DPRs). The pathogenic effects of G4C2 expansion transcripts have been targeted using approaches aimed at promoting their degradation, inhibiting nuclear export or silencing transcription. Other promising strategies include immunotherapy to reduce the DPRs themselves, reducing RAN translation, removing the repeats using DNA or RNA editing and manipulation of downstream disease-altered stress granule pathways. Finally, understanding the molecular triggers that lead to pheno-conversion may lead to opportunities that can delay symptomatic disease onset. Summary A large body of evidence implicates RAN-translated DPRs as a main driver of C9-ALS/FTD. Promising therapeutic strategies for these devastating diseases are being rapidly developed with several approaches already in or approaching clinical trials

The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P = .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally

Should I Stay or Should I Go? Firm Heterogeneity in the Post-crisis Period

Existing microeconomic research on exporting firms is dominated by empirical findings across time and countries based on two theories of why firms choose to export. One requires firms to be better performers before entry, the other requires there to be improvements in performance as a result of entry. In this paper, we disentangle entry to, and exit from, the overseas market for UK manufacturing firms to better understand the motivations and characteristics underlying both decisions. We explore the extent to which changes in the macroeconomic environment may influence behaviour, following a time of global financial turbulence