2014 Epilepsy Benchmarks Area III: Improve Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects

The Epilepsy Benchmark goals in Area III focus on making progress in understanding and controlling seizures and related conditions as well as on developing biomarkers and new therapies that will reduce seizures and improve outcomes for individuals with epilepsy. Area III emphasizes a need to better understand the ways in which seizures start, propagate, and terminate and whether those network processes are common or unique in different forms of epilepsy. The application of that knowledge to improved seizure prediction and detection will also play a role in improving patient outcomes. Animal models of treatment-resistant epilepsy that are aligned with etiologies and clinical features of human epilepsies are especially encouraged as necessary tools to understand mechanisms and test potential therapies. Antiseizure therapies that target (either alone or in combination) novel or multiple seizure mechanisms are prioritized in this section of the Benchmarks. Area III goals also highlight validation of biomarkers of treatment response and safety risk, effective self-management, and patient-centered outcome measures as important areas of emphasis for the next five to ten years

Opportunities for improving animal welfare in rodent models of epilepsy and seizures

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

Monetary Policy and Long-Term Real Rates

Abstract Changes in monetary policy have surprisingly strong effects on forward real rates in the distant future. A 100 basis-point increase in the 2-year nominal yield on an FOMC announcement day is associated with a 42 basis-point increase in the 10-year forward real rate. This finding is at odds with standard macro models based on sticky nominal prices, which imply that monetary policy cannot move real rates over a horizon longer than that over which all prices in the economy can readjust. Rather, the responsiveness of long-term real rates to monetary shocks appears to reflect changes in term premia. One mechanism that may generate such variation in term premia is based on demand effects coming from "yield-oriented" investors. We find some evidence supportive of this channel. * We thank John Campbell, Gene Fama, Emmanuel Farhi, Robin Greenwood, Anil Kashyap, David Scharfstein, Larry Summers, Adi Sunderam, Paul Tucker, Luis Viceira, and seminar participants at Harvard University for helpful comments. The analysis and conclusions set forth are those of the authors and do not indicate concurrence by other members of the Board of Governors.

Sociodemographic differences in linkage error: An examination of four large-scale datasets

© 2018 The Author(s). Background: Record linkage is an important tool for epidemiologists and health planners. Record linkage studies will generally contain some level of residual record linkage error, where individual records are either incorrectly marked as belonging to the same individual, or incorrectly marked as belonging to separate individuals. A key question is whether errors in linkage quality are distributed evenly throughout the population, or whether certain subgroups will exhibit higher rates of error. Previous investigations of this issue have typically compared linked and un-linked records, which can conflate bias caused by record linkage error, with bias caused by missing records (data capture errors). Methods: Four large administrative datasets were individually de-duplicated, with results compared to an available 'gold-standard' benchmark, allowing us to avoid methodological issues with comparing linked and un-linked records. Results were compared by gender, age, geographic remoteness (major cities, regional or remote) and socioeconomic status. Results: Results varied between datasets, and by sociodemographic characteristic. The most consistent findings were worse linkage quality for younger individuals (seen in all four datasets) and worse linkage quality for those living in remote areas (seen in three of four datasets). The linkage quality within sociodemographic categories varied between datasets, with the associations with linkage error reversed across different datasets due to quirks of the specific data collection mechanisms and data sharing practices. Conclusions: These results suggest caution should be taken both when linking younger individuals and those in remote areas, and when analysing linked data from these subgroups. Further research is required to determine the ramifications of worse linkage quality in these subpopulations on research outcomes

A comparative-advantage approach to government debt maturity’,

Abstract We study optimal government debt maturity in a model where investors derive monetary services from holding riskless short-term securities. In a setting where the government is the only issuer of such riskless paper, it trades off the monetary premium associated with short-term debt against the refinancing risk implied by the need to roll over its debt more often. We then extend the model to allow private financial intermediaries to compete with the government in the provision of short-term, money-like claims. We argue that if there are negative externalities associated with private money creation, the government should tilt its issuance more towards short maturities. The idea is that the government may have a comparative advantage relative to the private sector in bearing refinancing risk, and hence should aim to partially crowd out the private sector's use of short-term debt

Monetary Policy and Long-Term Real Rates

Abstract Changes in monetary policy have surprisingly strong effects on forward real rates in the distant future. A 100 basis point increase in the two-year nominal yield on a Federal Open Markets Committee announcement day is associated with a 42 basis point increase in the ten-year forward real rate. This finding is at odds with standard macro models based on sticky nominal prices, which imply that monetary policy cannot move real rates over a horizon longer than that over which all prices in the economy can readjust. Instead, the responsiveness of long-term real rates to monetary shocks appears to reflect changes in term premia. One mechanism that could generate such variation in term premia is based on demand effects due to the existence of what we call yield-oriented investors. We find some evidence supportive of this channel. JEL classification: E43, E52, G12, G1