Market impact under a new regulatory regime: Credit rating agencies in Europe

We investigate whether there are any identifiable differences in market perceptions of rating news released by Moody’s, S&P and Fitch following the establishment of a new regulatory regime in July 2011, when the European Securities and Markets Authority assumed responsibility for rating agencies’ regulation in Europe. We focus the analysis on the impact of bank rating actions on stock returns and volatility during 2008-2013. Among the intended effects of the new regulatory regime are reduced market impact of rating actions and enhanced market stability, yet we find very mixed evidence. Differentials in market responses across CRAs are identified

A biomechanical evaluation of the combined elevation test

This paper was accepted for publication in the journal Physical Therapy in Sport and the definitive published version us available at http://dx.doi.org/10.1016/j.ptsp.2016.11.001.Objectives: To biomechanically evaluate the relationships between the outcome of the Combined Elevation Test, its component joint motions, and thoracic spine angles. Design: Cross-sectional study. Setting: Laboratory. Participants: 18 elite swimmers and triathletes (11 males and 7 females). Main outcome measures: Combined Elevation Test outcome in forehead and chin positions. Individual joint contributions to test outcome. Results: No sex differences were found in test components, or between head positions. Test outcome was greater in the forehead position than the chin position (34.3 cm vs 30.2 cm; p<0.001). The variables most strongly associated with test outcome were glenohumeral joint flexion (r = 0.86 – 0.97; p<0.001), and shoulder retraction (r = 0.75 - 0.82; p<0.001). Total thoracic spine angle related strongly to test outcome in females (r = -0.77 – -0.88; p<0.05), but not in males (r = -0.17 – -0.24; p>0.05). Conclusions: The Combined Elevation Test is an effective screening tool to measure upper limb mobility into shoulder flexion and scapula retraction in both sexes, and thoracic extension in women. It is recommended that the test be performed in the forehead position. If a subject performs poorly on the test, follow up assessments are required to identify the impairment location

Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer's disease

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aβ plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aβ and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with Aβ and tau

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes